The document discusses the history and state of biomaterials and their use in medical applications. It notes that while biomaterials were originally developed for other uses, more recent biomaterials have been specifically designed for use in the body. The document outlines some current biomaterials like titanium alloys and hydroxyapatite used in orthopedic and dental applications. It also discusses the need for new biomaterials that can better integrate with tissues and serve as scaffolds for tissue engineering and developing artificial organs.

1. Biomaterials – A New HorizonSharath GhoshB100243048002266950<br />Biomaterials – A New Horizon<br />A paper submitted to<br />Dr. Prithwis Mukharjee<br />In partial fulfilment of the requirements of the course<br />Business Information Systems<br />On 07/11/2010<br />By Sharath Ghosh<br />B10024<br />Praxis Business School<br />Abstract<br />During the last decade’s considerable attention have been directed towards the use of implants using biomaterials. Biomaterials are intended to interface with biological system to evaluate and treat tissue, organs or functions of the body. But biomaterials so far are disable to become a part of body systems, they are still an alien material for the body. This work is based on the development of biocompatible biomaterials using tissue-engineering, made artificially but when inside the host will be a part of body system and act accordingly. This revolution will coincide with the increase in overall human survivability, regeneration theories, efficient systems and repair mechanisms.<br />The Idea – An Overview<br />Introduction:<br />There is a big demand for bio-materials to assist or replace organ functions and to improve patients’ quality of life. Materials options include metals, ceramics and polymers. Unfortunately the conventional materials are used that were not specifically developed for biological applications. Interaction between biomaterials and natural tissues is an important subject for biomaterial science and have a huge scope ahead. Such information is essential to aid the design of new biocompatible biomaterials.Source : www.mediligence.com<br />State of the art biomaterials:<br />Biomaterials are widely used in medical and dental treatment but their effectiveness is questionable. Almost all were developed for general use. Some alloys and hydroxyapatites were introduced in orthopaedic and dental fields and satisfactory results were obtained. Hydroxyapatite has the advantage that it connects to natural hydroxyapatite in bone. Toxicity must be avoided but inertness is not a high priority in biomaterials. Unfortunately metallic and ceramic biomaterials are not suitable to to replace soft tissues because of markedly different mechanical properties. Conventional polymers are used for many of today’s disposable medical devices but new functional biomaterials are awaited. Biomaterials have already successfully impacted the orthopaedic market segment. The invention of new facilitating technology will not only modify research in this field but with the increase in its applications the market will be bigger by time. Source : www.mediligence.com<br />Future visions:<br />Replacing natural organs with artificial ones causes difficulties when they do not function properly. However, artificial organs are necessary to support part or all of their essential functions, thereby improving quality of life. Artificial kidneys are one example. At present artificial hearts are only used temporarily to keep patient alive prior to organ transplantation. Availability of transplantable organs is strictly limited. New functional biomaterials are needed to improve artificial organs.<br />Non-thrombogenic artificial surfaces are an essential target for synthesis. There have been many proposals to provide blood compatible surfaces. This will increase the efficiency and take this science in the next level. Immobilization of hepain and urokinase, and introduction of poly-ethylene oxide chains on the surface are promising. Accumulation of plasma proteins on the blood contracting surfaces must be minimized. Preparation of multifunctional biomaterials such as non thrombogenic elastomers and permeable membranes, is a future challange.<br />Allograft Technology has a huge market. This technology will boost up the investments in this field.<br /> Source : www.mediligence.com<br />Future Needs and Priorities:<br />Artificial organs must be connected to our bodies during use but methods of connection still need to be researched. Infection at the interface is an unsolved problem in medical devices and artificial organs. Encapsulation around implanted biomaterials is essential for implantable biosensors which will be the outstanding gift of medical science to human civilization. But this technology is yet to be invented. Other emerging technologies around biomaterials are how to join each artificial blood vessel with patient’s natural blood vessels by the innovation of durable bonds between artificial organs and human tissues. Biocompatible blood access is also required for dialysis patients. <br />Source: Biomaterials by John B Park<br />Good scaffold is needed for cells and tissues other than gelatine and collagen. A three dimentional biomatrix is important for tissue engineering, especially to make hybridized artificial organs such as artificial liver support system.<br />Internal Research Programme needs :<br />Hard dental tissues do not have effective wound healing characteristics and do not regenerate, this was not initially realized by dental researched and clinicians. Clinicians believe that they could provide durable prosthesis to fix defects but the cut tissue did not heal and suffered invasion of micro-organisms. This is termed “secondary caries”. Connecting artificial materials to artificial tissues including tooth substrates will be a huge contribution in this field. Invention of pseudo-wound-healing characteristics will revolutionize the medical world. It is expected that hybridized dental tissue together with impermeable and acid resistant artificial enamel could resolve many problems in dentistry. Dental biomaterials may eliminate many dental defects in hard tissue and rejuvenate their function.<br />Non thrombogenic biomaterials are widely used in the development of artificial hearts but there are difficulties in their preparation. Artificial hearts are available as a temporary measure to bridge the transfer during heart transplantation even without non-thrombogenic substrates. The inner surface of blood vessels is composed of bio membranes whose main components are phospholipids. It has been suggested that methacrylate with phospholipid polar groups might be used at the membrane interphaseas the polymer surfaces could accumulate phospholipids when in contact with body fluids. 2-Methacryloyloxyenthylphosphorylchloride can be prepared and the characteristics of copolymers can be evaluated. Such copolymers are non-thrombogenic, highly hypophillic and, permeable, transluscent and do not accumulate bio active proteins on the surface. Bio-compatibility of several artificial surfaces could be improved by coating. This technology could open up revolutionary implementations of the use of such artificially designed organs and advanced medical devices.<br />3028950190500Conclusion:<br />Patients with several handicaps require new type biomaterials to improve their quality of life by assisting, recovering and reconstructing diseased or lost functions or organs. Connecting biomaterial science with tissue engineering will be a huge contribution to mankind. For example dialysis membranes keep more than 500 thousand chronic kidney patients every year. Tissue engineering has limitations and work is in hand to prepare new functional biomaterials with sufficiently strong mechanical properties. Good scaffolds are also needed for tissue engineering. Biotechnology based on gene science offers useful methods of producing effective materials for medical devices and artificial organs.<br />Source : www.bb.ustc.edu.cn<br />The Idea – Detailed Analysis<br />History<br />Replacing body parts, and especially hard tissues, dates back centuries by use of natural or synthetic materials. For instance, the Etruscans learned to substitute missing teeth with bridges made from artificial teeth carved from the bones of oxen, and in the 17th century a piece of dog skull was successfully transplanted into the damaged skull of a Dutch duke. The Chinese recorded the first use of dental amalgam to repair decayed teeth in the year 699 AD, and the pre-Colombian civilization used gold sheets to heal cranial cavities following trepanation. However, many other implantations failed as a result of the selected materials.<br />The safe use of materials to replace body parts did not come into practice until the advance of aseptic surgical techniques at the end of the 19th century. For decades attempts have been made to repair or replace hard tissues by various means. At first antilogous bone was used by grafting usually requires a second surgerical procedure. To overcome this shortage allogenic bone was taken into consideration, but its clinical performance is inferior as compared with autologous bone. In addition in load bearing applications, such as teeth or hip implants, bulk grafts cannot be used functionally. Instead, metals and non-degradable ceramics have been used because of their resistance to fatigue and high tensile strength. Until 1960s, materials used to replace body parts were borrowed from other industrial domains, and some of these are still widely used. Since 1960s materials specifically designed for body repair have been processed and used in clinical settings.<br />Regardless of their composition or application, materials used for body repair must meet both bio functionality and biocompatibility. Biocompatibility concerns the ability of the implant to perform the purpose for which it is designated. <br />Biomaterials can be defined as a material that is used to make devices to replace a part or a function of the body in a safe, reliable, economic and physiologically acceptable manner. It is a synthetic material used to replace part of living system or to function intimate contact with living tissue.<br />CompositionTypeClinical ApplicationsPropertiesTitanium & AlloysCeramicBone ReplacementsLoad Bearing SitesHip/Dental ProsthesisSpinal CasesBone Bonding (Bioactivity)Non corrosive, high specific strengthLow elasticity modulusBoneComposite MineralsProteinsBone Void FillerCartilage RegenerationSimilar Composition as the last boneBiodegradableNatural Source of ProteinsCollagenProteinHard and Soft Tissue RegenerationBiodegradableFibrinProteinSoft Tissue RepairSealing CapacityPoly-ethyleneCo-PolymerCement stopperBone void fillerSoft Tissue regenerationDrug DeliveryTurnability by varying molecular weight of degradation and mechanical propertiesBioactivity<br />Till now application of biomaterials are limited. But there exist a huge scope of tissue repairment using biomaterials and tissue engineering technology. The resources and technology is available and the research on this have already started. This will bring a new mode to medical science.<br />Towards Smart Designs to repair Tissues<br />Smart Design of Tissue Repair<br />Bio mimetic materials for skeleton repair : Learning from nature, in order to synthesize its product is a challenge. In tissue regeneration, nature offers smart, adaptive materials inspiring us to synthesize similar performing products, known as biochemistry concept. This concept can be used in biomaterials field.

2. Functional biometrics is the primary goal in designing biomaterials where tissue function should be restored.

3. Material biomimetism, where restoration of organ function is assumed to be obtained if the tissues are themselves imitated

4. Biological bimimetism, where restoration of tissue is synthetically stimulated by implanted cells or molecules that are involved naturally in the mechanism of tissue formation or function.Bio mimetic materials for Hard Tissues<br />Bone possesses self generation capacity. Biomaterials can be developed having the similar characteristics that will be a part of the body system. In mammals, the complete reconstitution of pre injured state is a unique feature for bone. The reconstruction of bones involves a primary blood invasion. The bone healing mechanism involves several phases and mechanisms. Research is going on modelling this mechanism and thereby developing appropriate biomaterial.

5. Regarding the substitution, the bio mimetic synthesis of biomaterials is based on bone bio mineralization that can be described as an extracellular preparation under appropriate physiological conditions. It offers several advantageous alternatives in favour of bone repair. As calcium phosphate ceramics are brittle, a bone like composite prepared under mild conditions and composed of an organic matrix and mineral crystal will open the possibility to use bio ceramics in load bearing applications. The bio mimetic method have been explored and researched which will lead to coatings on implant substrates or powdery compounds

6. Simulated body fluids, supersaturated with respect to apatite are being developed that will be used to synthesize bone like crystals. it will require a heterogeneous substrate onto which nucleation and crystallization will occur over time from fluids supersaturated with apatatic phase.Bio mimetic materials for Soft Tissues<br />Polymers can be fused with bioactive peptides to create biological responsive hydro gels. This concept will repair bone and cartilage tissues. This approach seeks to mimic the tissue extracellular matrix with hydro gel matrices that incorporates various biological signalling moieties. This will allow partial cell migration and partial degradation. Various researches are being conducted on this concept.

7. Fibrillar architecture has led to the design of polymers. These structures can now be fabricated at the nanometre scale which is essential for providing signals to the cells in the biological environment.

8. Bio mimetic synthesis is an emerging and promising technology with various clinical technologies better than classical approaches.1895475-190500Tissue Engineering<br />The last two decades have seen a surge in creative ideas and technologies developed to tackle the problem of repairing and replacing diseased or damaged tissues leading to the emergence of new fields in healthcare technology. Tissue engineering is an indiciplinary field that applies principles and methods engineering and life sciences towards the development of biological substitutes that restore, maintain and improve the function of damaged tissues and organs.<br />2447925732790The modern concept of tissue engineering is of great use for biomaterial science. Tissues can be extracted from body (sample) and regenerated, modified and then again inserted to host. Even tissues can be studied and artificially tailor made specific tissues can be prepared by and inserted in host. This is a new horizon to the biomaterial science.<br />The figure illustrates the technology:<br />Cells are harvested from tissues and isolated invitro

9. These cells can then be made proliferate invitro

10. Seeding in 3D and cultivated in bioreactor conditions to produce viable constructs

11. The most sophisticated strategy to prepare scaffold consists of design via 3D computer aided technique from a 3D CT scans of the body part to be replaced.

12. The final cell scaffold construct is implanted is implanted back into patients where tissue formation takes place.Source : Biochemistry by Lehninger<br />Instructed physic-chemical and biological processes at biomaterial interfaces<br />-66675850265There is a great gap in the complexity, hierarchy and intelligence between tissues and their potential substrates. A detailed understanding of the interactions between biomaterials, cells, fluids and tissues is mandatory. With this knowledge we will be able to engineer smarter materials capable of instructing their biological milieu for complete tissue regeneration. In vivo, the interactions between the implants <br />Source : Biomaterials by John B Park<br />and its biological environment occurs in non equilibrium conditions. The amount of the compounds playing a role in this interaction remains undefined. Regardless of the nature of the biomaterial, its biomaterial, its surrounding evolves with time.<br />Micro and nano designs of Biomaterials<br />Cell dimensions generally range from 5-100µm. Regardless their types, cells can react to micrometer and nanometre scales. The realization that the physical features of the substratum on which cells are growing affect their migration. but with the advent of nano fabrication methods the complexities of biomaterial science have been reduced much. Invitro micro features with specific shapes and sizes can be applied on biomaterials which can influence cellular activities.<br />Presence of nanophases in titanium oxide, alumina and hydroxyapatite substrate could have consequences on bone cell activities and functions. This theory has been a positive factor for biomaterial science and thus can provide edge to biomaterials.<br />This is backed up by several techniques like electron beam lithography, colloidal resiste, self assembling systems, casting, micro contact printing and particle synthesis. This are now a day’s already used to create nanotopography on organic and inorganic surfaces.<br />Micro and nano patterning can include modifications of surface chemistry or topology. Nano patterning can consist as well at grafting chemical functions onto biomaterials. In the field of tissue engineering, grafting technology has been seeking a major attention. Their presence on surface of biomaterials will facilitate improves cell adhesion.<br />23336259525Biomaterials in Gene Transfer<br />Gene transfer has been a benchmark in medical science for years. It is widely used in treatments, experiments, etc. Gene transfer is a commonly used technique. The complexity is selection of the right source that will contain the gene and invade the host. The gene and the carrier must be compatible of successful functions. The speciality of biomaterials lies in compatibility factor. So biomaterials can be used for the similar purpose. The advantage is that the cost will reduce. Also the carrier can be tailor-made and can perform its own operations and boost up the transfer and even facilitate without any side effects. Source : www.bentham.org<br /> Gene transfer has a huge application worldwide and a lot of money involved. Not only in the major level but gene transfer is also used in minor levels. The advantage of biomaterials is the compatibility, control, safety and it is biodegradable i.e., it gets degraded after the work is done without any harmful effects.<br />Multidrug Delivery<br />Biomaterials as per their characteristics and advantages will be the most reliable carrier for multi drug delivery. Biomaterials can even be more useful as it can facilitate the drug functions. These are safe and can be controlled. The control factor will give the edge over classical methods. It can also take part in the cellular functions and operations for drug mechanism or facilitating drug actions. Another factor is that these biomaterials are degradable which means safe disposal without any adverse effects on the body.<br />Countries InvolvedResearch InstitutionsCompanies InvolvedUSAUniversity of TorontoGenzyme Corp.JapanStanford UniversityFoster-Miller Inc.ChinaUniversity of PittsburghLife Cell Corp.UKUniversity College of LondonEnsion Inc.<br />Acknowledgement:<br />Much of the work presented here is based on the valuable contribution of many researchers working on biomaterials and tissue generations and the books written by various authors. The names are mentioned in the references below.<br />References:<br />Biomaterials as Stem Cell Niche by Springer

13. Biomaterials and Bioengineering by Donald El Wise

14. Biomaterials Principles and Applications John B Park