Biodegradable polymer Matrix Nanocomposites for Tissue Engineering
Biodegradable PolymerMatrix NanocompositesFor Tissue EngineeringAnand Singh 09MT3904Nandan Kumar 09MT1027Piyush Verma 09MT3018 Department of Metallurgical and Materials Engineering IIT Kharagpur
Tissue Engineering• Use of cells to repair the damaged biological tissue, leaving only natural substances to re-establish organ function.• Challenge: appropriate design and fabrication of porous, biodegradable, and biocompatible scaffolds.
What are Scaffolds?• Cells are often implanted or seeded into an artificial structure capable of supporting 3-D tissue formation called Scaffolds.• Scaffolds act as substrate for cellular growth, proliferation, and support for new tissue formation.
Biomaterials• Materials used for tissue engineering applications must be designed to stimulate specific cell response at molecular level.• Characteristics: Direct cell attachment, proliferation, differentiation, and extracellular matrix production and organization.
Objective• Fundamental requirements of biomaterials: i. biocompatible surfaces ii. favourable mechanical properties.• Conventional single-component polymer materials cannot satisfy these requirements.• Multi-component polymer systems
Why Nanotechnology?• Biological components, such as DNA, involve nano-dimensionality, hence it has logically given rise to the interest in using nanomaterials for tissue engineering.• Enables the development of new systems that mimic the complex, hierarchical structure of the native tissue.• Nanomaterials have inherent high surface area-volume ratio• Available polymeric porous scaffolds revealed insufficient stiffness and compressive strength
Nanocomposites• Nanocomposite materials often show an excellent balance between strength and toughness• Major Factor: Interface adhesion between nanoparticles and polymer matrix• Mechanical properties are dependant on i. properties of the matrix ii. properties and distribution of the fillers iii. interfacial bonding iv. synthesis or processing methods• Surface modification of nanostructures is needed to promote better dispersion of fillers and to enhance the interfacial adhesion.
Polymer Matrices For Bio-nanocomposites• Polymers are the primary materials for scaffold fabrication• Major Types:-1) Natural-based materials: Biological recognition, poor mechanical properties, limited in supply, costly. Eg. Polysaccharides (starch, alginate, chitin/chitosan, hyaluronic acid derivatives) or proteins (soy, collagen, fibrin gels, silk)2) Synthetic polymers: relatively good mechanical strength, shape and degradation rate can be easily modified, surfaces are hydrophobic, lack of cell-recognition signals. Eg. Poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(3-caprolactone) (PCL), poly (hydroxyl butyrate) (PHB)
Nanostructures For Bio-nanocomposites Hydroxyapatite (HA)• Hydroxyapatite (Ca10(PO4)6(OH)2) is the major mineral component (69% wt.) of human hard tissues• It possesses excellent biocompatibility with bones, teeth, skin and muscles• Promotes faster bone regeneration, and direct bonding to regenerated bone without intermediate connective tissue.• Problems: i. brittleness of the HA ii. lack of interaction with polymer
Contd.. Metal nanoparticles• Nanoparticles of noble metals exhibit significantly distinct physical, chemical and biological properties from their bulk counterparts• Their electromagnetic, optical and catalytic properties of noble-metal nanoparticles such as gold, silver and platinum, are strongly influenced by shape and size• Aim: To obtain small particle sizes, narrow size distributions and well-stabilized metal particles.• Silver (Ag) has been known to have a disinfecting effect and has been commercially employed as antimicrobial agent.• Problem: They are easily aggregated because of their high surface free energy, and they can be oxidized or contaminated in air.
Contd.. Carbon nanostructures• Fullerenes, carbon nanotubes (CNTs), carbon nanofibres (CNFs), graphene and a wide variety of carbon related forms.• Regular geometry gives CNT excellent mechanical and electrical properties.• By dispersing a small fraction of carbon nanotubes into a polymer, significant improvements in the composite mechanical strength have been observed. a) Covalent Functionalization: Fluorine, radicals, amine groups, etc. are attached to the CNT sidewall, play a determinant role in the mechanism of interaction with cells. b) Non-covalent attachment: SWCNTs is not damaged and their properties remain intact, forces between the polymer and the SWCNTs are very weak
Contd..• Electrospun using a high voltage power supply at 20 kV potential between the solution and the grounded surface• The PLLA/HA mixture was loaded in a 20mL glass syringe equipped with a blunt 23 gauge needle• The ground collector (9 cm in diameter) located at a fixed distance of 15 cm from the needle.• The flow rate of the solution and the spinning time were set to 0.85mL/h and 8 h, respectively
Contd.. Foaming Technology:• Objective - To produce porous structure in matrix.• Material used to produce porosity-Supercritical CO₂• Matrix – Poly Lactic Acid (PLA)• Reinforcement – Nano Hydroxy Apatite (nHA) PLA Hydroxy Apatite
Contd..Why PLA?• Biodegradable (Gradually transforms loads to the bone as organ heals) (Medical implants in the form of screws, pins, rods, and as a mesh)Why supercritical CO₂ ?• Non-toxic, non- flammable , noncorrosive, abundant, inexpensive, commercially available in high purity, and readily accessible supercritical conditions ( Critical Temperature = 31.1˚C and Critical pressure = 7 37MPa)Why nHA ?• Nanocrystalline HA (nHA) enhances osteoblast adhesion and surface deposition of calcium- containing materials. (with respect to Bone-tissue growth).• Inorganic calcium-containing constituent of bone matrix and teeth, imparting rigidity to these structures
Contd.. Steps involved: • Firstly amorphous or semi- crystalline polymer is saturated with CO₂ at temperature 31.1 and pressure 7.37 Mpa, with the diﬀusion of gas into polymer matrix, it forms single-phase polymer/CO₂ solution. • When the equilibrium is reached, pressure is reduced or temperature is increased or both, so that the supercritical CO₂ turns into gas and escape out of the polymer leaving pores
Applications• Fracture fixation• Interference Screws• Meniscus Repair• Suture anchors• Suture coating• Dental and orthopedic implants• Drug delivery
References• Z.C.Xing, S.J.Han, Y.S.Shin and I.K.Kang, Fabrication of Biodegradable Polyester Nanocomposites by Electrospinning for Tissue Engineering, Journal of Nanomaterials, v 2011, pp 1-18• X.Shi, J.L.Hudson, P.P.Spicer, J.M.Tour, R.Krishnamoorti and A.G.Mikos, Injectable Nanocomposites of Single-Walled Carbon Nanotubes and Biodegradable Polymers for Bone Tissue Engineering, Journal of Biomacromolecules, v 7, 2006, pp 2237- 2242• Xia Liao, Haichen Zhang, and Ting He, Preparation of Porous Biodegradable Polymer and Its Nanocomposites by Supercritical CO2 Foaming for Tissue Engineering, Journal of Nanomaterials, Volume 2012, Article ID 836394, pp 1-12.