This document discusses encapsulation techniques for non-parenteral drug and cell delivery. It presents Prof. Ian Marison's research at Dublin City University on using encapsulation for high cell density cultures and microcapsule characterization. Specific examples discussed include encapsulating the antibiotic geldanamycin and NSAIDs to allow their selective removal from environments and downstream purification. The research aims to develop novel encapsulation methods for bioprocessing applications such as increasing product yields from degradation environments.
1. Drug release scaffolds can be categorized as cell delivery scaffolds or drug delivery scaffolds, with common parameters including 3D architecture, porosity, composition, interfaces, degradability, and mimicking the ECM.
2. Specific parameters for drug release scaffolds include loading capacity, drug distribution, binding affinity, and stability.
3. Injectable hydrogel scaffolds show advantages over implantation scaffolds for drug release, including enabling sustained release upon swelling to control release behavior with minimal invasiveness.
Tissue engineering is defined as an interdisciplinary field that applies engineering and life science principles to develop biological substitutes that restore or improve tissue function. It involves understanding tissue growth principles to produce functional replacement tissue for clinical use. Examples include artificial skin, bone, pancreas, and bone marrow. Tissue engineering utilizes living cells as engineering materials, such as fibroblasts for skin repair. Cells are extracted from tissues and embedded in scaffolds to support tissue formation.
Tissue engineering uses scaffolds, cells, and signaling molecules to regenerate tissues and organs. Scaffolds provide a structure for cell attachment, growth, and tissue formation. Natural polymers like collagen and hyaluronic acid, and synthetic polymers like poly-lactic-co-glycolic acid are commonly used as scaffold materials. Scaffolds can be fabricated using various methods including freeze drying, electrospinning, 3D printing, and textile technologies to produce scaffolds with desirable properties like porosity and pore size for tissue growth. Scaffolds seeded with stem cells or tissue-specific cells aim to repair and regenerate tissues for applications in skin, bone, cartilage, and other organs.
TISSUE DEVELOPMENT WITH TISSUE ENGINEERING APPROACHFelix Obi
Tissue Engineering is the development and practice of combining scaffolds, cells, and suitable biochemical factors (regulatory factors or Signals) into functional tissues. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or improve damaged tissues or whole organs.
Cells are the building blocks of tissue, and tissues are the basic unit of function in the body. Generally, groups of cells make and secrete their own support structures, called extracellular matrix. This matrix, or scaffold, does more than just support the cells; it also acts as a relay station for various signaling molecules. Thus, cells receive messages from many sources that become available from the local environment. Each signal can start a chain of responses that determine what happens to the cell. By understanding how individual cells respond to signals, interact with their environment, and organize into tissues and organisms, Tissue Engineers are now able to manipulate these processes to amend damaged tissues or even create new ones.
Biomaterials for tissue engineering slideshareBukar Abdullahi
An overview of Tissue Engineering with some basics in Biomaterials and Synthetic Polymers. Further references should be considered as I presented this a specific target audience.
The document summarizes advancements in 3D bioprinting and electrospinning techniques for fabricating tissue scaffolds and enabling cell growth from 1998 to 2014. It describes key studies that used 3D printing and electrospinning to create scaffolds from various polymers for tissue engineering applications. The studies demonstrated improved cell adhesion, proliferation and infiltration on 3D printed and electrospun scaffolds compared to traditional fabrication methods. The techniques continued to advance through the use of additional biomaterials and the creation of hybrid and multilayered scaffold structures.
The document discusses scaffolds for tissue engineering. It defines scaffolds as temporary or permanent artificial extracellular matrices that accommodate cells and support 3D tissue regeneration. Scaffolds aim to mimic the natural extracellular matrix and promote cell response to engineer replacement tissues. The key requirements for scaffolds are that they be porous, biocompatible, and have properties matching the target tissue. Various fabrication techniques can be used to control the scaffold architecture, composition, and other properties. Common scaffold materials discussed include natural polymers like collagen and synthetic polymers.
Polymeric scaffolds are important in tissue engineering as they act as synthetic frameworks to support cell growth and tissue regeneration. There are various types of scaffolds including hydrogels, fibrous, and porous scaffolds. Scaffolds can be made from natural or synthetic polymers using different fabrication techniques. It is important for scaffolds to have appropriate mechanical properties, surface properties, porosity, and degradation rate to effectively support tissue growth.
1. Drug release scaffolds can be categorized as cell delivery scaffolds or drug delivery scaffolds, with common parameters including 3D architecture, porosity, composition, interfaces, degradability, and mimicking the ECM.
2. Specific parameters for drug release scaffolds include loading capacity, drug distribution, binding affinity, and stability.
3. Injectable hydrogel scaffolds show advantages over implantation scaffolds for drug release, including enabling sustained release upon swelling to control release behavior with minimal invasiveness.
Tissue engineering is defined as an interdisciplinary field that applies engineering and life science principles to develop biological substitutes that restore or improve tissue function. It involves understanding tissue growth principles to produce functional replacement tissue for clinical use. Examples include artificial skin, bone, pancreas, and bone marrow. Tissue engineering utilizes living cells as engineering materials, such as fibroblasts for skin repair. Cells are extracted from tissues and embedded in scaffolds to support tissue formation.
Tissue engineering uses scaffolds, cells, and signaling molecules to regenerate tissues and organs. Scaffolds provide a structure for cell attachment, growth, and tissue formation. Natural polymers like collagen and hyaluronic acid, and synthetic polymers like poly-lactic-co-glycolic acid are commonly used as scaffold materials. Scaffolds can be fabricated using various methods including freeze drying, electrospinning, 3D printing, and textile technologies to produce scaffolds with desirable properties like porosity and pore size for tissue growth. Scaffolds seeded with stem cells or tissue-specific cells aim to repair and regenerate tissues for applications in skin, bone, cartilage, and other organs.
TISSUE DEVELOPMENT WITH TISSUE ENGINEERING APPROACHFelix Obi
Tissue Engineering is the development and practice of combining scaffolds, cells, and suitable biochemical factors (regulatory factors or Signals) into functional tissues. The goal of tissue engineering is to assemble functional constructs that restore, maintain, or improve damaged tissues or whole organs.
Cells are the building blocks of tissue, and tissues are the basic unit of function in the body. Generally, groups of cells make and secrete their own support structures, called extracellular matrix. This matrix, or scaffold, does more than just support the cells; it also acts as a relay station for various signaling molecules. Thus, cells receive messages from many sources that become available from the local environment. Each signal can start a chain of responses that determine what happens to the cell. By understanding how individual cells respond to signals, interact with their environment, and organize into tissues and organisms, Tissue Engineers are now able to manipulate these processes to amend damaged tissues or even create new ones.
Biomaterials for tissue engineering slideshareBukar Abdullahi
An overview of Tissue Engineering with some basics in Biomaterials and Synthetic Polymers. Further references should be considered as I presented this a specific target audience.
The document summarizes advancements in 3D bioprinting and electrospinning techniques for fabricating tissue scaffolds and enabling cell growth from 1998 to 2014. It describes key studies that used 3D printing and electrospinning to create scaffolds from various polymers for tissue engineering applications. The studies demonstrated improved cell adhesion, proliferation and infiltration on 3D printed and electrospun scaffolds compared to traditional fabrication methods. The techniques continued to advance through the use of additional biomaterials and the creation of hybrid and multilayered scaffold structures.
The document discusses scaffolds for tissue engineering. It defines scaffolds as temporary or permanent artificial extracellular matrices that accommodate cells and support 3D tissue regeneration. Scaffolds aim to mimic the natural extracellular matrix and promote cell response to engineer replacement tissues. The key requirements for scaffolds are that they be porous, biocompatible, and have properties matching the target tissue. Various fabrication techniques can be used to control the scaffold architecture, composition, and other properties. Common scaffold materials discussed include natural polymers like collagen and synthetic polymers.
Polymeric scaffolds are important in tissue engineering as they act as synthetic frameworks to support cell growth and tissue regeneration. There are various types of scaffolds including hydrogels, fibrous, and porous scaffolds. Scaffolds can be made from natural or synthetic polymers using different fabrication techniques. It is important for scaffolds to have appropriate mechanical properties, surface properties, porosity, and degradation rate to effectively support tissue growth.
Tissue engineering aims to reconstruct tissues and organs by growing new tissue from cells onto a scaffold. It provides an alternative to transplantation by producing tissues customized for patients. Recent advances include improved scaffold materials for bone tissue engineering using osteoinductive and hybrid materials. Scientists have also engineered heart and nerve tissues that closely mimic natural tissues, with the heart tissue even beating when implanted. Tissue engineering holds promise for treating currently untreatable medical conditions but further research is still needed.
This document provides an overview of the field of tissue engineering. It defines tissue engineering as an interdisciplinary field that applies engineering and life science principles toward the development of biological substitutes that restore or improve tissue function. The key goals of tissue engineering are to repair, replace, or regenerate tissues and whole organs. Current clinical treatments involve grafting methods like autografts, allografts, and xenografts, but these have limitations like immune rejection and donor scarcity. Tissue engineering aims to address these issues by using scaffolds, cells, and growth factors to regenerate tissues. Challenges in the field include properly mimicking the tissue microenvironment, scaling up production, and developing vascularization within engineered tissues.
This document discusses tissue engineering approaches and cell sources. It defines tissue engineering as using cells, engineering, and materials to improve or replace biological functions. Tissue engineering offers opportunities like creating implants and studying stem cells. The main approaches are using instructive environments to guide regeneration, delivering cells/factors, and culturing cells on scaffolds. Sources of cells discussed include induced pluripotent stem cells, fetal/umbilical cord cells, and various adult cells like mesenchymal stem cells. Scaffolds are also discussed as a key element, with properties like porosity and factors released. Both in vitro and in vivo strategies can be used.
Introduction
Definition
History
Principle
Cell sources
What cells can be used?
Scaffolds
Biomaterials
Bioreactor
How tissue engineering is done?
How does tissue engineering differ from cloning?
Tissue engineering of specific structures
Application of tissue engineering
Limitations
Conclusion
References
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physicochemical factors to improve or replace biological functions.
The term has also been applied to efforts to perform specific biochemical functions using cells within an artificially-created support system (e.g. an artificial pancreas, or a bio artificial liver).
A commonly applied definition of tissue engineering, as stated by Langer and Vacanti is “An interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve [Biological tissue] function or a whole organ”
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
Tissue engineering aims to combine scaffolds, cells, and growth factors to regenerate tissues. Periodontal tissue engineering specifically focuses on regenerating damaged periodontal tissues through the use of scaffolds, stem cells, growth factors, and gene therapy. Tissue engineering combines materials science, cell biology, and medical sciences to repair or reconstruct tissues. Bone tissue engineering is an emerging field that uses these techniques to treat bone diseases by overcoming limitations of traditional treatments.
The document summarizes recent applications of tissue engineering principles in orthopaedics. It discusses how scaffolds, signals, and cells have been combined in various tissue engineering strategies to treat fracture nonunions, osteonecrosis, and chondral/osteochondral defects. For fracture nonunions, delivering mesenchymal stem cells on an atelocollagen scaffold improved healing rates. Treating osteonecrosis with autologous mesenchymal stem cells seeded on bone grafts showed prevention of disease progression in some cases. Cell doses and scaffold properties were found to influence outcomes. Tissue engineering approaches for cartilage defects, including cell injections and composite scaffolds, demonstrated symptom improvement over baseline.
1) The document discusses the concept of an in vivo bioreactor (IVB), which aims to produce organs and tissues within the body by bypassing traditional tissue engineering steps. 2) Key criteria for an IVB include identifying a location with pluripotent cells, establishing an environment excluding other cells, presenting a single cue overriding biological noise, and defining a regenerative volume. 3) Early successes include engineering bone and cartilage in vivo through injection of calcium alginate or agarose gels in the subperiosteal space to direct cell fate.
This document discusses tissue engineering and the use of scaffolds for growing cells. It describes several scaffold design techniques including nanofibre self-assembly, gas foaming, CAD/CAM technologies, and electrospinning. Scaffolds provide a structure for cells to attach, migrate, and grow into tissues. The future of this technology could enable the creation of more complex organs and possibly whole bodies. However, issues around cost and ethics will need to be addressed as the technology advances.
A fun activity to teach the concept of tissue engineering to students and even kids! This was developed by the Binghamton BMES student chapter and also used as a case study submission for the Biomaterials class by the developers of this idea. It will showcase at the Binghamton University 2016 Engineers Week for young students in the local community.
This document provides an overview of tissue engineering. It discusses that tissue engineering applies engineering and life science principles to develop biological substitutes that restore or enhance tissue function. It is an alternative to drug therapy, gene therapy, and organ transplantation. The document summarizes key components of tissue engineering including appropriate cell sources, biomaterials to support cell growth, and placing the engineered construct in vivo. It also reviews extracellular matrix composition and role, growth factors, and cell-matrix interactions important for tissue engineering.
This document discusses tissue engineering and its application to periodontal regeneration. It defines tissue engineering as using engineering and life science principles to generate biological substitutes to restore lost function. The key components of tissue engineering are scaffolds, cells, and signaling molecules. Scaffolds provide structure for cells to migrate into defects and can deliver growth factors and cells. Mesenchymal stem cells and periodontal ligament stem cells show potential for periodontal regeneration. Growth factors like PDGF and IGF promote neovascularization and osteogenesis. Tissue engineering using scaffolds, stem cells and growth factors has shown success in animal studies and holds promise to achieve complete periodontal regeneration.
This document provides an overview of tissue engineering. It discusses the process of tissue engineering which involves using a scaffold material, seeding it with living cells, using growth factors, and implanting the new tissue. It also describes different types of stem cells, materials used for scaffolds, and methods to synthesize tissue engineered scaffolds. Applications of tissue engineering include bioartificial organs and tissues like skin, bone, and blood vessels. Both advantages and disadvantages of the field are mentioned.
HYDROGELS FOR WOUND HEALING AND TISSUE ENGINEERING APPLICATIONSMunira Shahbuddin
This document summarizes research on hydrogels and their applications in tissue engineering, regenerative medicine, and wound healing. It describes several key findings:
1) Hydrogels from konjac glucomannan were shown to stimulate proliferation of fibroblasts and keratinocytes in a concentration-dependent manner and support their metabolic activity.
2) Crosslinking konjac glucomannan formed hydrogels that maintained viability of fibroblasts and keratinocytes. The hydrogels inhibited contraction and promoted re-epithelialization in a human tissue engineered skin model.
3) Analysis found the hydrogels modulated water content and interactions to influence cell-matrix interactions important for wound healing and tissue regeneration applications.
1. Tissue engineering involves growing tissues or organs in vitro to replace damaged body parts. Cells are seeded onto a scaffold and bathed in growth factors to grow new tissue.
2. Common scaffolds include collagen, polymers like PLLA, and ceramics. Cells used include stem cells, keratinocytes for skin, and bladder cells.
3. The process involves obtaining cells, seeding them onto a scaffold, and incubating the construct to grow new tissue which can then be implanted.
Unit-4 discusses the bioartificial pancreas as a treatment for type 1 diabetes. It involves encapsulating pancreatic islets within semi-permeable membranes to prevent immune rejection while allowing insulin and nutrients to pass through. Three main methods of encapsulation are described: macroencapsulation of large numbers of islets within implantable devices, microencapsulation of single islets or clusters within hydrogel capsules, and surface modification of islets with coatings like PEG. Both extravascular and intravascular macroencapsulation devices are discussed, along with various hydrogel materials used for microencapsulation like alginate, agarose, and PEG. Challenges include preventing clotting, ensuring
This document discusses tissue engineering and its applications in artificial skin and cartilage. It begins by defining tissue engineering as applying engineering and life science principles to develop biological substitutes that restore or improve tissue function. It then discusses the goals of tissue engineering, including restoring biomechanical and physiological function. The document outlines different types of cells used, including autologous, allogeneic, xenogeneic and stem cells. It provides details on different tissue culture techniques and goes on to describe artificial skin and cartilage, including their history, manufacturing processes, cell sources and advantages/disadvantages.
This document summarizes a seminar presentation on tissue engineering. It defines tissue engineering as using cells, biomaterials, and biochemical factors to develop biological substitutes that restore or maintain tissue function. It discusses cells, stem cells, tissues, and provides examples of tissue engineering applications including bioartificial livers and pancreases. The presentation focuses on the bioengineering approach to creating a bioartificial pancreas using islets of Langerhans cells to secrete insulin in response to glucose levels. Key design challenges are keeping the cells alive and protected from the immune system while allowing for nutrient exchange.
This document discusses obtaining bioceramics from shark teeth for potential use in bone tissue engineering. Shark teeth were characterized using SEM, TEM, and micro-CT scans to analyze their enameloid and dentine composition. The teeth then underwent ball milling, pyrolysis at 950°C, and sieving to produce biological apatite granules with isolated fluorapatite nanocrystals. Preliminary biocompatibility tests of the granules showed optimal cell attachment and proliferation over 21 days, demonstrating their potential for bone tissue engineering applications.
This study encapsulated equine endothelial progenitor cells and mesenchymal stem cells alone and in co-culture within a PEG-fibrinogen hydrogel scaffold to assess neovascularization. Equine EPCs formed tubules within 1 day when encapsulated alone or with MSCs, and vascularization increased over 4 days. Tubules did not form with MSCs alone. The hydrogel scaffold supported long-term cell viability and vascular structure formation, demonstrating its potential for tissue engineering and wound healing applications in horses. Future work will quantify vessel formation to determine scaffold thickness and MSC effects.
Tissue engineering aims to reconstruct tissues and organs by growing new tissue from cells onto a scaffold. It provides an alternative to transplantation by producing tissues customized for patients. Recent advances include improved scaffold materials for bone tissue engineering using osteoinductive and hybrid materials. Scientists have also engineered heart and nerve tissues that closely mimic natural tissues, with the heart tissue even beating when implanted. Tissue engineering holds promise for treating currently untreatable medical conditions but further research is still needed.
This document provides an overview of the field of tissue engineering. It defines tissue engineering as an interdisciplinary field that applies engineering and life science principles toward the development of biological substitutes that restore or improve tissue function. The key goals of tissue engineering are to repair, replace, or regenerate tissues and whole organs. Current clinical treatments involve grafting methods like autografts, allografts, and xenografts, but these have limitations like immune rejection and donor scarcity. Tissue engineering aims to address these issues by using scaffolds, cells, and growth factors to regenerate tissues. Challenges in the field include properly mimicking the tissue microenvironment, scaling up production, and developing vascularization within engineered tissues.
This document discusses tissue engineering approaches and cell sources. It defines tissue engineering as using cells, engineering, and materials to improve or replace biological functions. Tissue engineering offers opportunities like creating implants and studying stem cells. The main approaches are using instructive environments to guide regeneration, delivering cells/factors, and culturing cells on scaffolds. Sources of cells discussed include induced pluripotent stem cells, fetal/umbilical cord cells, and various adult cells like mesenchymal stem cells. Scaffolds are also discussed as a key element, with properties like porosity and factors released. Both in vitro and in vivo strategies can be used.
Introduction
Definition
History
Principle
Cell sources
What cells can be used?
Scaffolds
Biomaterials
Bioreactor
How tissue engineering is done?
How does tissue engineering differ from cloning?
Tissue engineering of specific structures
Application of tissue engineering
Limitations
Conclusion
References
Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physicochemical factors to improve or replace biological functions.
The term has also been applied to efforts to perform specific biochemical functions using cells within an artificially-created support system (e.g. an artificial pancreas, or a bio artificial liver).
A commonly applied definition of tissue engineering, as stated by Langer and Vacanti is “An interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve [Biological tissue] function or a whole organ”
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
Tissue engineering aims to combine scaffolds, cells, and growth factors to regenerate tissues. Periodontal tissue engineering specifically focuses on regenerating damaged periodontal tissues through the use of scaffolds, stem cells, growth factors, and gene therapy. Tissue engineering combines materials science, cell biology, and medical sciences to repair or reconstruct tissues. Bone tissue engineering is an emerging field that uses these techniques to treat bone diseases by overcoming limitations of traditional treatments.
The document summarizes recent applications of tissue engineering principles in orthopaedics. It discusses how scaffolds, signals, and cells have been combined in various tissue engineering strategies to treat fracture nonunions, osteonecrosis, and chondral/osteochondral defects. For fracture nonunions, delivering mesenchymal stem cells on an atelocollagen scaffold improved healing rates. Treating osteonecrosis with autologous mesenchymal stem cells seeded on bone grafts showed prevention of disease progression in some cases. Cell doses and scaffold properties were found to influence outcomes. Tissue engineering approaches for cartilage defects, including cell injections and composite scaffolds, demonstrated symptom improvement over baseline.
1) The document discusses the concept of an in vivo bioreactor (IVB), which aims to produce organs and tissues within the body by bypassing traditional tissue engineering steps. 2) Key criteria for an IVB include identifying a location with pluripotent cells, establishing an environment excluding other cells, presenting a single cue overriding biological noise, and defining a regenerative volume. 3) Early successes include engineering bone and cartilage in vivo through injection of calcium alginate or agarose gels in the subperiosteal space to direct cell fate.
This document discusses tissue engineering and the use of scaffolds for growing cells. It describes several scaffold design techniques including nanofibre self-assembly, gas foaming, CAD/CAM technologies, and electrospinning. Scaffolds provide a structure for cells to attach, migrate, and grow into tissues. The future of this technology could enable the creation of more complex organs and possibly whole bodies. However, issues around cost and ethics will need to be addressed as the technology advances.
A fun activity to teach the concept of tissue engineering to students and even kids! This was developed by the Binghamton BMES student chapter and also used as a case study submission for the Biomaterials class by the developers of this idea. It will showcase at the Binghamton University 2016 Engineers Week for young students in the local community.
This document provides an overview of tissue engineering. It discusses that tissue engineering applies engineering and life science principles to develop biological substitutes that restore or enhance tissue function. It is an alternative to drug therapy, gene therapy, and organ transplantation. The document summarizes key components of tissue engineering including appropriate cell sources, biomaterials to support cell growth, and placing the engineered construct in vivo. It also reviews extracellular matrix composition and role, growth factors, and cell-matrix interactions important for tissue engineering.
This document discusses tissue engineering and its application to periodontal regeneration. It defines tissue engineering as using engineering and life science principles to generate biological substitutes to restore lost function. The key components of tissue engineering are scaffolds, cells, and signaling molecules. Scaffolds provide structure for cells to migrate into defects and can deliver growth factors and cells. Mesenchymal stem cells and periodontal ligament stem cells show potential for periodontal regeneration. Growth factors like PDGF and IGF promote neovascularization and osteogenesis. Tissue engineering using scaffolds, stem cells and growth factors has shown success in animal studies and holds promise to achieve complete periodontal regeneration.
This document provides an overview of tissue engineering. It discusses the process of tissue engineering which involves using a scaffold material, seeding it with living cells, using growth factors, and implanting the new tissue. It also describes different types of stem cells, materials used for scaffolds, and methods to synthesize tissue engineered scaffolds. Applications of tissue engineering include bioartificial organs and tissues like skin, bone, and blood vessels. Both advantages and disadvantages of the field are mentioned.
HYDROGELS FOR WOUND HEALING AND TISSUE ENGINEERING APPLICATIONSMunira Shahbuddin
This document summarizes research on hydrogels and their applications in tissue engineering, regenerative medicine, and wound healing. It describes several key findings:
1) Hydrogels from konjac glucomannan were shown to stimulate proliferation of fibroblasts and keratinocytes in a concentration-dependent manner and support their metabolic activity.
2) Crosslinking konjac glucomannan formed hydrogels that maintained viability of fibroblasts and keratinocytes. The hydrogels inhibited contraction and promoted re-epithelialization in a human tissue engineered skin model.
3) Analysis found the hydrogels modulated water content and interactions to influence cell-matrix interactions important for wound healing and tissue regeneration applications.
1. Tissue engineering involves growing tissues or organs in vitro to replace damaged body parts. Cells are seeded onto a scaffold and bathed in growth factors to grow new tissue.
2. Common scaffolds include collagen, polymers like PLLA, and ceramics. Cells used include stem cells, keratinocytes for skin, and bladder cells.
3. The process involves obtaining cells, seeding them onto a scaffold, and incubating the construct to grow new tissue which can then be implanted.
Unit-4 discusses the bioartificial pancreas as a treatment for type 1 diabetes. It involves encapsulating pancreatic islets within semi-permeable membranes to prevent immune rejection while allowing insulin and nutrients to pass through. Three main methods of encapsulation are described: macroencapsulation of large numbers of islets within implantable devices, microencapsulation of single islets or clusters within hydrogel capsules, and surface modification of islets with coatings like PEG. Both extravascular and intravascular macroencapsulation devices are discussed, along with various hydrogel materials used for microencapsulation like alginate, agarose, and PEG. Challenges include preventing clotting, ensuring
This document discusses tissue engineering and its applications in artificial skin and cartilage. It begins by defining tissue engineering as applying engineering and life science principles to develop biological substitutes that restore or improve tissue function. It then discusses the goals of tissue engineering, including restoring biomechanical and physiological function. The document outlines different types of cells used, including autologous, allogeneic, xenogeneic and stem cells. It provides details on different tissue culture techniques and goes on to describe artificial skin and cartilage, including their history, manufacturing processes, cell sources and advantages/disadvantages.
This document summarizes a seminar presentation on tissue engineering. It defines tissue engineering as using cells, biomaterials, and biochemical factors to develop biological substitutes that restore or maintain tissue function. It discusses cells, stem cells, tissues, and provides examples of tissue engineering applications including bioartificial livers and pancreases. The presentation focuses on the bioengineering approach to creating a bioartificial pancreas using islets of Langerhans cells to secrete insulin in response to glucose levels. Key design challenges are keeping the cells alive and protected from the immune system while allowing for nutrient exchange.
This document discusses obtaining bioceramics from shark teeth for potential use in bone tissue engineering. Shark teeth were characterized using SEM, TEM, and micro-CT scans to analyze their enameloid and dentine composition. The teeth then underwent ball milling, pyrolysis at 950°C, and sieving to produce biological apatite granules with isolated fluorapatite nanocrystals. Preliminary biocompatibility tests of the granules showed optimal cell attachment and proliferation over 21 days, demonstrating their potential for bone tissue engineering applications.
This study encapsulated equine endothelial progenitor cells and mesenchymal stem cells alone and in co-culture within a PEG-fibrinogen hydrogel scaffold to assess neovascularization. Equine EPCs formed tubules within 1 day when encapsulated alone or with MSCs, and vascularization increased over 4 days. Tubules did not form with MSCs alone. The hydrogel scaffold supported long-term cell viability and vascular structure formation, demonstrating its potential for tissue engineering and wound healing applications in horses. Future work will quantify vessel formation to determine scaffold thickness and MSC effects.
NICE is a new module technology developed by Apollon Solar that uses glass-glass encapsulation without the need for soldering or adhesives. It provides reliable, high performance modules through a simpler production process. Apollon Solar has partnered with Energy Industrie in Tunisia to build a 30 MW production line. Testing shows the NICE modules experience very low degradation and passed IEC certification. Development continues on bifacial and busbar-free cell versions to further improve yields.
The document summarizes the work done at the Liu Nanobionics Lab, which focuses on biomaterials, tissue engineering, and nanotechnology. The lab studies how biomaterials interact with biological systems, develops tissue engineering approaches using scaffolds and growth factors, and modifies material surfaces at the nano-scale to enhance biocompatibility. It also explores techniques like 3D printing and electrospinning to control scaffold architecture for tissue regeneration applications.
The document discusses biomaterials, which are materials used in medical applications that interact with biological systems. It defines biomaterials and outlines their history, characteristics, examples of applications like implants and grafts, challenges, and future potential. Key biomaterial properties include biocompatibility, mechanical compatibility with tissues, and ability to perform specific functions. Common biomaterials are metals, ceramics, polymers, and composites used in devices like heart valves, dental implants, and orthopedic implants.
Filip bzik proteins in the lens of the eyeFilip Bzik
This study examined the distribution and role of the Cadm1 protein in the mouse lens. The research found that Cadm1 is highly abundant in the epithelial cells and fiber cells of the one-month old wild-type lens. Cadm1 was also found to be equally present in the regular structured fiber cells of 2-3 day old wild-type lenses. However, lenses from Cadm1 knockout mice at this age showed disorganized membranes, indicating Cadm1 is important for maintaining lens cellular structure. The study concludes Cadm1 plays a key role in the lens and is found at highest levels in epithelial and fiber cell membranes.
This project aims to establish an immortalized cell line from dermal fibroblasts of the axolotl Ambystoma mexicanum to study molecular pathways of limb regeneration in vitro. Primary dermal fibroblasts will be cultured from axolotl skin tissue and optimized for growth through various media additives. The cells will then be immortalized using SV40 LT antigen and validated through assays to confirm identity and genetic stability. The resulting cell line will provide a tool to investigate regeneration at the molecular level without in vivo experiments.
Fibrocell Science is a regenerative medicine company focused on developing autologous cell therapies using a patient's own fibroblast cells. Their lead product, LAVIV, is the first FDA-approved cell-based therapy for treating nasolabial folds and has shown encouraging results in clinical studies. Fibrocell has additional programs in development for indications like acne scarring, burn scars, and vocal cord scarring. The company is working to expand their fibroblast platform to new areas of aesthetic dermatology and regenerative medicine through additional clinical trials and development projects.
Plant cells can be immobilized through various methods like surface attachment, entrapment in porous matrices, containment behind barriers, and self-aggregation. This allows maintaining high cell densities to increase productivity of secondary metabolites. Immobilization provides advantages like easier product separation, continuous processing, and protecting cells from shear forces. However, limitations include additional costs, complexity in understanding plant cell pathways, and potential loss of biosynthetic capacity. Applications of immobilized plant cells include production of high-value compounds, biotransformations, and synthetic seed technology.
This document describes research into the microbial synthesis of platinum nanoparticles using Saccharomyces boulardii and evaluation of the anticancer activity of the synthesized platinum nanoparticles. Key findings include:
1) Platinum nanoparticles were successfully synthesized using the cell free extract of S. boulardii when reacted with chloroplatinic acid.
2) Various parameters like metal salt concentration, temperature, cellmass concentration, pH, and reaction time were optimized to control the yield and properties of the synthesized nanoparticles.
3) The synthesized platinum nanoparticles showed anticancer activity against A431 and MCF-7 cell lines with IC50 values between 57-100 μg/ml, indicating potential for use as an antic
Presentation of Richard Murphy for the Workshop on Hydrolysis Route for Cellulosic Ethanol from Sugarcane.
Apresentação de Richard Murphy realizada no "Workshop on Hydrolysis Route for Cellulosic Ethanol from Sugarcane"
Date / Data : February 10 - 11th 2009/
10 e 11 de fevereiro de 2009
Place / Local: Unicamp, Campinas, Brazil
Event Website / Website do evento: http://www.bioetanol.org.br/workshop1
This document discusses topics related to industrial biotechnology including fermentation products, microorganisms used in fermentation, and historical and future applications of industrial biotechnology. It provides classifications of microorganisms including prokaryotes and eukaryotes. Details are given on bacterial cell structure, essential and non-essential components. Methods for classifying bacteria such as gram stain and morphological characteristics are also summarized.
Javier Amayra - Biotechnological Screening in Animal Cell Cultureponenciasexpoquim11
The document discusses bioprocess development for animal cell culture. It highlights that screening phases are important but have reproducibility issues when scaling up. The HexaScreen and HexaBatch systems aim to address these issues by providing (1) an automated and controlled multi-vessel screening platform, (2) low volume bioreactors to better mimic industrial scales, and (3) monitoring of key parameters like cell growth, pH and oxygen to improve screening accuracy and translation to later phases. This helps streamline bioprocess optimization from initial screening through production.
Reverse membrane bioreactor seminar pptnirvarna gr
This document introduces reverse membrane bioreactors (rMBRs) as a new technology for biofuel production. rMBRs use diffusion instead of pressure to retain cells inside membrane modules placed in bioreactors. A case study is presented where an rMBR using a flat sheet membrane successfully facilitated simultaneous glucose and xylose consumption from synthetic media and pretreated wheat straw hydrolysate by yeast cells. The rMBR also enabled in situ detoxification of inhibitors. Testing confirmed the rMBR facilitated the required cell agglomeration for co-utilization of sugars and was effective for prolonged fermentation without contamination.
Snehal term paper- advances in microencapsulation techniquessnehal dhobale
The document discusses various encapsulation technologies used to encapsulate probiotics, food ingredients, and nutraceuticals. It describes techniques like co-extrusion processes and nozzle vibration technology that are used to form capsules. Specific examples discussed include encapsulating sweet orange oil, peppermint oil, and propolis extract using complex coacervation. Microencapsulation and nanoencapsulation techniques provide benefits like improved shelf life, taste masking, and controlled release. The technologies can be used to develop functional foods and nutraceutical products.
Develop an understanding of Taxonomy (classification) of Oral Microorganisms
Describe how to obtain samples from Oral Cavity
Describe Molecular techniques of identification
Describe techniques that requires culture for identification
This document summarizes Michael Buschmann's work on nanomedicine at Ecole Polytechnique. It discusses how nanomedicine uses nano-sized tools for diagnosis, prevention and treatment of disease. Some key applications of nanomedicine include drug delivery via liposomes and polymeric nanoparticles. The document also outlines the requirements for successful nanomedicine research and development, including efficacy, safety, manufacturing and regulatory approval. Buschmann's group works on developing chitosan-based nanoparticles for gene delivery applications.
This document discusses tissue engineering of the nasal septum using a chitosan-based material. Chitosan is derived from crustacean shells and has advantages like biodegradability and biocompatibility. The author creates a hybrid polymer by mixing a chitosan solution with hyaluronic acid and collagen. Human inferior turbinate tissue is treated and seeded onto the collagen-coated hybrid polymer. Morphological examinations are conducted to analyze pore size, cell proliferation, ciliary beat, histology, and immuno-histochemistry. The goal is to develop a tissue-engineered nasal septum with sufficient control over shape and improved biocompatibility for cell seeding.
Somatic hybridization is a technique used to produce hybrid plants by fusing protoplasts (plant cells without cell walls) from two different plant species or varieties. There are several key steps:
1. Isolation of protoplasts from plant tissues using either mechanical or enzymatic methods. Enzymatic methods using cellulase and pectinase enzymes are more common.
2. Fusion of the protoplasts using chemical fusogens like polyethylene glycol (PEG) or physical methods like electrofusion. This results in hybrid cells called heterokaryons.
3. Selection and culture of the hybrid cells using techniques like antibiotic resistance or genetic markers.
4. Regeneration
Defined, consistent quality: The only all-in-one solution to simplify algae engineering:
GeneArt® Algae Engineering Kits for rapid production. Previously, algae research and production labs relied on poorly characterized, non-optimized cell stocks and cloning tools for their work. Preparing growth medium was convoluted and time-consuming, and growth rates and yields from the transformed cells were disappointing. New GeneArt® Algae Engineering Kits for Chlamydomonas reinhardtii and Synechococcus elongatus are the first commercially available genetic modification and expression systems for photosynthetic microalgae. These kits are designed for rapid scale-up and production and consistent, defined quality.
Chitosan-hayluronic acid composite for tissue engineeringArun kumar
1) The document proposes using a chitosan-based scaffold material for tissue engineering of the nasal septum. Chitosan is derived from crustacean shells and has advantages like biodegradability and biocompatibility.
2) The method involves creating a hybrid polymer by mixing a 2% chitosan solution with hyaluronic acid and collagen. This polymer scaffold would provide structure for cell seeding.
3) Human inferior turbinate tissue was harvested and the cells were seeded onto the collagen-coated scaffold. Morphological examination and analysis of DNA content and cilia movement would then assess proliferation and function.
Antioxidant, collagen synthesis activity in vitroPuja Saha
1) The document discusses a study on the anti-wrinkle effects of a cream containing 2% Veronica officinalis extract. Cell culture and clinical tests were conducted to evaluate antioxidant and collagen synthesis activity.
2) In cell tests, the extract showed good cytotoxicity and increased collagen production in fibroblasts. DPPH radical scavenging assays found the active compound verbascoside and extract to be effective antioxidants.
3) A 58-day clinical trial on 21 women applied the extract cream to one wrinkled area and a placebo to the other. Measurements found the extract cream significantly reduced wrinkle area and length compared to the placebo.
This document provides an introduction to the subject of biotechnology for a 6th semester B Pharmacy course. It discusses key topics including the objectives and learning outcomes of the course, an overview of modules to be covered such as enzyme immobilization, biosensors, protein engineering and genetic engineering. Specific techniques in these areas like methods of enzyme immobilization and applications of biosensors are explained. The benefits, applications and future potential of biotechnology in fields like medicine, agriculture, food and industry are also summarized.
Grainne Flynn was diagnosed with diabetes in 1993 and began her journey of diabetes education and peer support that empowered her as a patient. She became involved in diabetes advocacy as a blogger, event organizer, and support group facilitator. Through education, family and peer support online and in support groups, she felt empowered in managing her diabetes.
This document outlines a modified diabetes care model called the Portsmouth Model or "Super Six." It describes the different patient populations and types of care provided at the hospital, primary care, and diabetes support team levels. The hospital team focuses on acute, pregnancy/pre-pregnancy, active foot disease, advancing CKD/RRT, type 1 diabetes including insulin pumps, and complex type 2 diabetes patients. Primary care manages those at risk of diabetes, with controlled type 2 diabetes, and uncontrolled type 2 diabetes with guidelines. The diabetes support team cares for uncontrolled type 2 diabetes patients and type 1 patients who do not attend appointments are invited to an online community. Patient numbers are provided for each group.
Gerald Tomkin , Director of the Diabetes Institute Beacon HospitalInvestnet
This document summarizes a presentation on diabetes, atherosclerosis, and cholesterol. It discusses how diabetes increases the risk of cardiovascular disease and mortality. It notes that achieving lipid targets substantially reduces cardiovascular risk, but that target achievement is still uncommon. New therapies that inhibit microsomal triglyceride transfer protein, apolipoprotein C3, proprotein convertase subtilisin/kexin type 9, and other targets may help lower lipids and reduce risk, but require further study of long-term safety and efficacy. The need to more intensively reduce risk factors to further lower cardiovascular event rates is emphasized.
Dr. Ronan Canavan , Clinical lead of the National Clinical Programme for Diab...Investnet
Ronan Canavan, a consultant endocrinologist, gave a presentation at the Future Health Summit on designing better diabetes care. The presentation discussed standards, an integrated care model, retinopathy screening and treatment, podiatry, education, and paediatrics. It reviewed a 1999 model of diabetes care and discussed progress made in the last 5 years, including establishing a clinical diabetes program, retinal screening, developing a model of care for diabetic foot care, and integrated diabetes nurse specialists. The presentation concluded by discussing how Ireland can be the best in areas like prevention, technology, and education.
This document presents information on CliniBridge, a behavioral analysis software platform for clinicians that is integrated with a mobile platform for patients and caregivers. The platforms were pilot tested with Sussex Community NHS Trust and aimed to 1) avoid patient relapses and readmissions to meet funding targets, 2) allow patients to self-manage for improved outcomes, 3) increase the effectiveness of therapy, and 4) use silent data and intervention systems. The platforms were presented by Dervilla O'Brien, Managing Director and Co-Founder of CliniBridge.
The document describes an app developed by Dr. Malcolm R. Kell and colleagues to help breast cancer survivors focus on physical activity, diet, and reducing their body mass index (BMI) after treatment. The free app allows users to select an exercise intensity, see how much exercise is needed over 10 weeks to lower BMI by 10%, update their BMI, and access simple recipes to support a healthy diet for weight loss. The goal is to provide breast cancer survivors a simple tool to promote healthy living and improved survivorship after breast cancer.
Serious problems require serious solutions. Alcohol misuse costs €57 billion annually and only 1 in 9 people who misuse alcohol receive treatment. A smartphone and web-based platform is proposed as an innovative, user-friendly, evidence-based, and cheaper way to provide personalized treatment at scale. The platform utilizes computerized cognitive behavioral therapy and text messaging, which studies have shown can be effective in treating alcohol misuse. It seeks to revolutionize the UK addiction treatment market and plans clinical trials in Ireland and the UK in 2016 before rolling out more broadly in Europe and the US.
Dr. Robert Kelly discusses pressures facing the Irish health system including resources, costs, quality, and efficiency. Barriers include doctors' limited time and resources, and patients' issues with access, time, mobility and costs. Telemedicine can help overcome these barriers by giving patients more convenient lower-cost access supported by information to high-quality care. VideoDoc is an Irish telemedicine platform provider that operates a virtual clinic model and enables doctors to integrate the platform into their practices to develop telemedicine solutions for patients. The platform aims to improve healthcare experiences and outcomes at affordable costs through more engaged patients.
Cathal Brennan , Medical Device Assessor- Human Products Authorisation and Re...Investnet
This document discusses the regulation of standalone software as a medical device. It begins by defining standalone software and noting the EU directive that amended the definition of a medical device to include software intended for medical purposes. It then covers how to qualify standalone software as a medical device and classify it. The document reviews essential requirements, harmonized standards, conformity assessment procedures including CE marking, and registration requirements. It provides advice for manufacturers on ensuring compliance and for users on reporting issues. The role of the Irish regulator HPRA in providing guidance and conducting oversight is also discussed.
This document summarizes the effects of digital distraction on human behavior and brain function. It notes that people now spend 2-3 times as much time online as a decade ago and most check social media daily and switch between devices over 20 times an hour. This constant connectivity is changing how our brain functions, shortening attention spans and affecting memory. The ability to stay focused without distraction has become a rare "superpower." However, the document also sees opportunities to make sense of data and provide tips to use technology in a supportive rather than substitutive way.
1) The document discusses using neuroimaging and machine learning to detect dementia earlier by predicting which patients with mild cognitive impairment (MCI) will progress to dementia within a year.
2) The researchers have developed a model that can predict MCI to dementia progression with 75% accuracy by analyzing brain MRIs.
3) They are working to improve their model's accuracy and to predict the biological brain age and time to dementia for patients.
Keregen Therapeutics is a UK-based early stage drug discovery and development company focused on developing precision medicines for Parkinson's Disease. They were founded in 2015 and are operating out of University College London and Stevenage Bioscience Catalyst. Keregen is developing first-in-class small molecule activators of the Nrf2 pathway as a disease-modifying treatment for Parkinson's with the goal of a safer oral therapy that can be taken once daily. The company has participated in accelerator programs, secured initial funding, hired new employees, and aligned with academia to access resources and personnel as they progress their lead candidate towards clinical trials.
Darren Cunningham, Inflection Bio SciencesInvestnet
Darren Cunningham, CEO of Inflection Bio, presented an overview of the company's mission to develop new cancer treatments by targeting the PIM kinase pathway. Inflection Bio has a pipeline of targeted therapeutics for cancers like multiple myeloma, NSCLC, and hematological malignancies. Its lead candidates inhibit both PIM and PI3K/mTOR to address resistance to existing therapies. The company utilizes a network of research collaborators and has raised €2.2 million to advance its preclinical programs, with the goal of securing partners after Phase I trials.
This document discusses developing more effective drug delivery systems for treating blindness linked to diabetes or aging. It describes Phision Therapeutics' work on developing novel small molecule drugs and biodegradable microcapsule formulations for sustained drug release over 4-6 months via microneedles, as an alternative to frequent eye injections. The founders aim to commercialize this technology to reduce the burden of treatment for patients and clinicians.
This document describes the development of the BraineyApp, a mobile application created by Niamh Malone to help with self-recovery and rehabilitation following acquired brain injuries like stroke or traumatic brain injury. The app provides a personalized recovery journey broken into weekly and monthly goals. It underwent user testing and focus groups. Funding is being sought to further develop prototypes with input from medical experts and technology companies to expand the app's reach and features to support recovery from various neurological conditions and surgeries.
Toby Basey-Fisher , CEO, Co Founder, Eva DiagnosticsInvestnet
Evadiagnostics provides a smart health solution that offers immediate blood testing and actionable patient information to help with triaging. Their clinically validated platform technology connects devices, software, and data to improve patient care through better planning and quality of care driven by new data insights. They were recently recognized as European winners for their award-winning team and significant health economic impact through health solutions that improve patient outcomes.
Ena Prosser, Fountain Healthcare PartnersInvestnet
This document summarizes information about a life sciences venture capital partnership. They have €170 million under management across two funds and invest in companies seeking €8-10 million or more that have large market potential and an acceptable level of risk. Their team includes experts across clinical, commercial, IP, manufacturing and legal areas. They take an active role in their investments and want to connect early with companies that have strong teams critical to success.
Raglan Capital is an investment firm based in Dublin that develops investment opportunities by identifying and sourcing proprietary projects. In recent years it has raised over $500 million for ventures in sectors like oil and gas, financial technology, online gaming, medtech, and life sciences. One of Raglan's recent successes was instrumental in the formation of Amryt Pharma, a rare disease drug company that listed on the London AIM exchange in April 2016 with a market capitalization of $50 million and $20 million in cash.
Academic institutions in Ireland are driving support and innovation in several ways:
1) Through technology transfer offices and innovation centers that work directly with industry to identify needs and fund applied research projects to develop solutions.
2) By establishing research centers organized around key industry sectors like food and agriculture that are jointly funded and driven by partnerships between academia and industry.
3) By offering degree programs, facilities, expertise and other resources to support industry-identified priorities and challenges in areas like biomedical technologies and brewing/distilling.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
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Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
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Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Top 10 Best Ayurvedic Kidney Stone Syrups in India
Prof Ian Marison, Director, National Institute for Bio-processing Research & Training, NIBRT
1. Encapsulation as a method for non-
parenteral drug and cell delivery
Prof. Ian W. Marison
Laboratory of Integrated Bioprocessing (LiB)
Dublin City University
National Institute of Bioprocessing Training & Research
(NIBRT)
2. Presentation outline
• Introduction: an example of an innovative NIBRT research
programme
• High cell density cultures by cell encapsulation
• Microcapsule characterisation
• Antibiotic encapsulation (geldanamycin)
• NSAID encapsulation
• And what about drug recovery from drinking water?
3. Biologicals – new challenges
Developing the Nation's Biosimilars Program
Steven Kozlowski et al. N Engl J Med 2011; 365:385-388 August 4, 2011
Complex compounds need an holistic, integrated
approach
4. Training and research for Industry:
transforming performance through
constructive partnership
5. An Innovative
Partnership
• National Institute for Bioprocessing Research and Training
• Created for industry – in partnership with industry
• Initially four leading academic institutions- expanding to
become a truly National facility e.g. incorporation of all 7
universities and Institutes of Technology
• Funded (€57 million) by the Irish Government (IDA
Ireland)
• Operated as a non-profit making company
7. Expression systems
Expression systems for the production of biopharmaceuticals in US
& EU
E. coli
Yeast
Other microbial cells
39%
CHO
Other animal cells
15%
1%
29%
16%
Figures from ”Expression systems for product and process improvements”,
Ronald A. Rader, BioProcess International, June 2008
8. Challenges of animal cell culture
• Solutions:
– Cell Encapsulation
– Process Analytical
Technology
• Need for high cell density
cultures
• Need for high level of
monitoring & control
9. Cell Microencapsulation
Capsule
(Micro-bioreactor)
Semi-permeable
capsule membrane
bioreactor
Viable cells
Nutrients
Shear Critical for the survival
stress Wastes of the cells
Proliferate
Recombinant Protein
10. Vibrating-Jet Technique
Size range 150 μm - 2 mm
and deviation of ± 1.5%
Liquid-core
Porous
membrane
Size range 200 μm - 2 mm
and deviation of ± 2.5%
Whelehan and Marison (2010). Journal of Microencapsulation 28: 669-688
11. Development of Novel Microcapsules
Aqueous two-phase system
– PEG and Dextran
Hydrogel
membrane
Dextran in
Polymer
• Potential impact • Present work
• • Obtaining required characteristics
High commercialization
possibilities • Cell Encapsulation
• Cells suspended within core
• Testing new polymers
12. Encapsulation of CHO cells
Preliminary experiment to optimize cell number in alginate microcapsules
Regular shaped and
intact microcapsules
Empty PLL-alginate
microcapsules
0.5x104 cells/ml alginate 1x104 cells/ml alginate
Irregular shaped
microcapsules
Difficulties in jet break up
2x104 cells/ml alginate 2.7x104 cells/ml alginate
*
CHO 320 Cells 104 / ml alginate 0 0.5 1 2 2.7
AVD Micro capsule ∅ (μm) (n=25 microcapsules) 321 +/- 7 335 +/-6 320+/-7 402 +/- 64 381 +/- 48
*Breguet, V. et al. (2007). Cytotechnology 53: 81-93
13. Removal of desired compounds from their associated environments LiB
Extraction aides for biotechnological and chemical processes
• Alginate hydrogel membrane • Liquid-core
• • Hydrophobic material
Chitosan, cellulose sulphate etc
• Oleic acid, vegetable oils etc
• Porous structure
Microcapsules
Further treatment
• Novel approach termed ‘Capsular Perstraction’
Capsular Perstraction Derived from permeation and
extraction
14. LiB
Geldanamycin
• Polyketide antibiotic
• Ansamycin family
• Streptomyces hygroscopicus var geldanus
• Received significant attention in 1980’s
• Novel antitumor antibiotic
Molecular structure Commercial Pelleted growth
of geldanamycin geldanamycin (magnification 40X)
15. ISPR of Geldanamycin
1.2
1
• Polyketide antibiotic 485 μm
0.8 598 μm
• Ansamycin family 751 μm
C(t)/C(0)
0.6
• Streptomyces hygroscopicus var geldanus
0.4
• Novel antitumour activity
0.2
• Produced at relatively low conc.
0
• Sensitive to process conditions 0 20 40 60 80
• Liquid-core microcapsules time (min)
• Increase productivity Rapid extraction of the antibiotic
from degradation environment
• 30% increase in geldanamycin
• 110 – 143 mg/l
• Removal from the hostile
culture environment
• Selectivity
• Downstream processing
• Reduced no. of steps
• Highly purified
No capsules Biomass growth
GA conc.
Whelehan & Marison (2011). Biotechnology Progress 27: 1068-1077 & Whelehan et al (2012) Journal of Bioscience and Bioengineering (in press)
16. Purification of Capsular Geldanamycin
+
Geldanamycin loaded
Capsules (selective removal) Empty capsules Very pure solution
for future use for purification
Agitate at Geldanamycin,
high speed acetonitrile
and small quantities
of oleic acid
Mix with acetonitrile
saturated with oleic acid Solution has a
higher affinity Removal of
oleic acid
Acetonitrile
removal Low temperature
distillation
Geldanamycin crystals (purity > 97%)
Crystal production
17. Application in other fields LiB
• Methodology for the treatment of drinking/waste-water
• Pharmaceuticals, pesticides and herbicides
120
Sulfamethoxazole
120
Metoprolol Ethylparathion
100
Furosemide 100
Clofibric Acid Methylparathion
80 Carbamazepine
80
% removed
Atrazine
% removed
Warfarin
Diclofenac
60 60 2,4 D
40 40
20 20
0 0
0 20 40 60 80 100 120 0 20 40 60 80 100 120
time (min)
time (min)
• Mechanism to degraded the extracted pollutant
Pollutant loaded Pseudomonas
capsule
Whelehan et al (2010). Water Research 44:2314-24 Wyss et al (2004). Biotech Bioeng 87:734-42
18. Determining characteristics of microcapsules
• Porosity
– HPLC with dextran standards
HPLC Chromatogram • Mechanical resistance (strength)
– Texture analyzer
• Burst Force
Before compression After compression
19. Data analysis & Management Atomic Force Microscope (AFM)
Techniques for capsule
Scanning Electron Microscope
(Cryo FE-SEM) characterisation
Confocal Scanning Laser Light Microscope
Microscope (CSLM)
20. DUAL STAINING OF LOW GRADE ALGINATE
POWDER
633nm laser 488nm laser
Polyphosphates- yellow
Algin -blue
Bar 5mm
Combined image
30. Are there cells protruding on the capsules surface?
Day 0
Day 3
Asylum MFP-3D
Day 4
Analysis Mode
No cell visible on
micro-capsule surface
31. Are the cells embedded in the capsule core?
Asylum MFP-3D
polymer CHO 320
Analysis Mode
AFM illustrates cell- polymer interaction
within the capsule core
39. “Oral Delivery of NSAIDs within the gastrointestinal (GI) tract to
improve systemic bioavailability, to reduce side effects and to
target release to regions of the GI tract to maximise systemic
absorption or enable localised delivery to diseased GI tissue”
Thanks to: Bernard McDonald:
Joint funded by Sigmoid Pharma and IRCSET
40. Introduction
Encapsulation Technology – Opportunity to address all issues
Enhanced Drug Solubility
• Drugs available in solubilised form
• ↑ Bioavailability
Enhanced Drug Permeability
• Drug passes into bloodstream
• Convert injection into oral
• ↑ Bioavailability
• Small Molecules
• Large Molecules
Opportunities • Peptides
Enhanced Drug Stability • Once Daily Dosing
• Controlled/Targeted release • Lower Dose
(Polymer coatings) • Less Side Effects
• Targeted Colonic delivery
• ↑ Bioavailability
40
41. Introduction
Encapsulation Approaches
Beads Capsules
Oil Core
Oil Droplets
Encapsulated in Gelatin Shell
Gelatin Matrix
API dissolved in oil/surfactant/co-solvent API dissolved in oil core,
mixture entrapped as droplets in a gelatin surrounded by gelatin
(or other material) matrix (or other material) shell
41
42. Introduction
Model Drug Selected: Celecoxib
• NSAID
• Poorly soluble
• COX-2 inhibitor (Cyclooxygenase-2 plays a role in inflammation)
• Typical indications: osteoarthritis, rheumatoid arthritis, acute pain
• Other indications: role in colorectal cancer prevention (reduces
number of colon and rectal polyps) and possible role in colon
cancer therapy. Large scale studies have been hindered by side
effects
42
43. Results – Liquid Formulations
Celecoxib Liquid Formulations produced using Optimal Liquid Vehicles
25 liquid formulations prepared containing celecoxib dissolved in combinations of
oils/surfactants/co-solvents and assessed via in-vitro dissolution testing
In-vitro Dissolution Testing
• Media maintained at 37 °C
• Paddle speed – 75 RPM
• Automatic sampling over 12 hours
• Use media to replicate intestinal conditions
- Simulated gastric fluid (pH 1.2)
- Simulated intestinal fluid (pH 6.8)
• All conditions chosen to replicate in-vivo conditions
• Dissolution testing referred to as release testing in the case of pre-dissolved dosage
forms
43
44. Results – Liquid Formulations
Dissolution Performance of Celecoxib API and Marketed Celecoxib Product
Celebrex® compared to that of selected Liquid Formulations
• Formulation CEL-021/L superior to Celebrex™ and API
• Formulation CEL-021/L superior to CEL-026/L. Drug fully
dissolved in both formulations therefore composition very important
44
45. Results – Optimised Microcapsule Formulations
Release of drug from optimised
formulations in excess of 80%
% of release dropped off after
12hrs. Need to apply controlled
release polymers to avoid drop-off
Performance of optimised
formulations superior to Celebrex™
Formulation CEL-136/B superior to
CEL-135/B via incorporation of
greater surfactant levels
45
46. Results – Physical Characterisation of Microcapsules
Correlation between Internal Structure and In-Vitro Performance
Large oil
droplets
= poor
dissolution
= likely poor
bioavailability
Small oil
droplets
= good
dissolution
= likely good
bioavailability
46
47. • Encapsulation of bioactives
• Functional foods • Global market size ~$75 billion (GBA,
2007)
Global functional
foods market USA >$20 billion; EU, Japan
8% growth globally; 14% USA
key segments: probiotic dairy ~$12 billion,
7% growth thru 2010; omega-3 ~$3 billion,
10% growth)
• Global market size forecast >$100
billion by ~2010
• Encapsulation of Folates
• Improved
• Stability of sensitive molecules (digestive system)
• Storage conditions i.e. handling
• Applicability etc
• Enterprise Ireland commercialization grant
48. Conclusions
• There are a number of innovative programmes in Ireladn in
the area of drug delivery of small and large molecules
• NIBRT would be an ideal vehicle for helping to coordinate
some of these activities
• Novel technologies exist for drug and cell delivery
• Novel technologies exist for drug and organics recovery
• Potential business opportunities exist to exploit these
• And what about drug recovery from drinking water?
49. Feel free to contact me:
Prof Ian Marison Executive Director ian.marison@nibrt.ie
Visits can be arranged at any time.
If we look at biologicals compared to chemical drug substances, we can immediately see why there is this additional amount of understanding needed. Here we have an aspirin molecule and a monoclonal antibody. The difference striking. Therefore, complex compounds need an holistic, integrated approach. Furthermore, complex compounds such as mAb needs correct glycosylation - need for animal cell expression system.
However, in this work we have achieved this by creating droplets of buffers of a defined composition containing water soluble materials which aide the formation and stability of the droplets. The technique is based on aqueous - 2 - phase systems using a PEG rich phase (core) and dextran rich phase (membrane). These materials help increase the viscosity/surfacetension of the core/membrane materials which enables the droplet to maintain its structure, whereby it can be hardened into a capsule. The picture above show two aqueous-core microcapsules produced using the co-extrusion technique as described above Future experiments will focus on trying to obtain consistently, the characteristics required by capsules (mentioned in previous slide) which are required if they are to be applied to a relevant medical or biotechnology production process. Most importantly experiments will involve the encapsulation of animal cells within the core by mixing the cells in the core material before direct extrusion with the shell material through the defined nozzle The droplets (microcapsules) will contain: (1) water soluble drugs or compounds which are extremely unstable and cannot normally be consumed orally. (2) Vitamin supplements (i.e. folates) for oral delivery, which are essential for the development and growth of healthy foetuses but are readily degraded in the gut. (3) Sensitive mammalian cells capable of producing important recombinant antibodies for use in the treatment of specific diseases and/or for producing diagnostic kits for the early detection of certain ailments and (4) adult stem cells to enable a 3-D platform for tissue production. It is anticipated that the controlled encapsulation of cells and compounds within a hydrogel membrane will help overcome the many problems currently facing the application of such materials in biotechnological and medical processes.
Pirkko’s results: 1.5 % Na-Alginate in MOPS washing buffer pH 7.0 and filtered with 0.2 micro filter Increasing number of CHO320 cells were mixed in 1.5% Na-Alginate for encapsulation to find optimal seeding cell number Polymerization: 100 mM CaCl2 in MOPS buffer pH 7.0 Result: Encapsulation of cells under 2 x 104 cells / ml alginate is producing regular shaped, intact micro capsules. Next step is to culture encapsulated cells to define the effects encapsulation in growth and define new limiting factors in the microenvironment. Also effects of encapsulation in production and product quality and stability are studied
Initially we performed experiments to see if capsules were capable of rapidly extractinbg geldanamycin from culture environments and from the graph it can be seen that microcapsules were capable of rapidly extracting the drug from culture environments and this shows the use of different sized capsules didn’t affect extraction speed. The second graph shows the affect of capsule addition on geldanamycin production and growth of the streptomyces with squares representing biomass growth and diamonds geldanamycin production. The red lines are capsule addition experiments. It was discovered that the addition of capsules at day 5 prevented them interfering with the cells. From the results it can be seen that microcapsule assisted fermentations resulted in a 30% higher maximum net concentration of geldanamycin compared to the control fermentation due to the removal of the antibiotic from a hostile fermentation environment. More importantly, the immediate in-situ extraction of the antibiotic resulted in the recovered material been stable in the culture environment for over 24 days whilst not affecting the growth of the bacteria. The process also resulted in a selective removal of the antibiotic, which aided downstream processing
After recovering the capsules from the fermentation using a very simplistic procedure our next goal was too see if we could recover high quantities of the geldanamycin from the capsules at high levels of purity so that the geldanamycin could be crystallized, whilst also maintaining the microcapsule structure so that they could be used for future experiments. We developed a simplistic procedure to enables to achieve this goal.