Tissue Engineering: a new healthcare technology Asma Yahyouche Biomaterials Group Department of Materials, University of Oxford Parks Road, Oxford, OX1 3PH, UK Biomaterials • Biomaterials science may be the most multidisciplinary of all the sciences which encompasses aspects of medicine, biology, chemistry, engineering and materials science. • Biomaterials are : “Non-viable materials used in a medical devices intended to interact with biological systems” [D.F. Williams, 1987] Biomaterials: Examples • • • • • • • • • • • Joint replacements Bone plates Bone cement Hip Joint Artificial ligaments and tendons Dental implants for tooth fixation Blood vessel prostheses Heart valves Skin repair devices Cochlear replacements Contact lenses Heart valve Knee joint Hip joint Skin Biomaterials at Oxford Biomaterials Group Materials Dept. Drug Delivery Systems Nano-SIMS characterization of Teeth In vitro Testing Tissue Engineering Cell culture Tissue expander Human Tissue Damage • Disease (e.g cancer, infection). • Trauma (e.g accidental, surgery). • Congenital abnormalities (e.g birth defects). • Current clinical treatment based on: Grafts and Transplants Artificial Biomaterials Organ transplant • High cost : $400B in USA each year US: 1July 2001- 30 June 2002 No. patients on waiting list No. patients received treatment No. Patients died waiting Cost per operation in 1987 Lung Heart 3 757 1 071 463 - 4 097 2 155 589 $ 110 000 Kidney Liver Pancreas 50 240 14 385 3 052 $ 30 000 17 379 5 261 1 861 $ 238 000 1 151 541 28 $ 40 000 Organ transplant [Cooper .T (1987): Human Organ Transplantation: Societal, medical-legal, regulatory, and Reimbursement Issues ed. Cowen D.H et al, Health Administration Press Ann Arbor, MI, pp. 19-26] Example: Bone Fractures in UK • Bone is second transplanted tissue after blood. • Healthcare in the United Kingdom alone set to cost over 900£ million each year. • Each year in the UK: 150,000 fractures due to osteoporosis • Hip fracture is associated with high morbidity and mortality. • 30-50% of these hip operations with require subsequent revision surgery. Total Hip Joint Replacement • • • 50,000 hip replacements (arthroplasties) in Britain each year. Hydroxyapatite porous coatings in orthopaedic prostheses: Bioactivity, Osteoconductivity. Problem: Infections in orthopedic surgery (10% of cases) Biomaterials • Prostheses have significantly improved the quality of life for many ( Joint replacement, Cartilage meniscal repair, Large diameter blood vessels, dental) • However, incompatibility due to elastic mismatch leads to biomaterials failure. Conclusion • Tissue loss as a result of injury or disease, in an increasing ageing population, provide reduced quality of life for many at significant socioeconomic cost. • Thus a shift is needed from tissue replacement to tissue regeneration by stimulation the body’s natural regenerative mechanisms. Tissue Engineering • National Science Foundation first defined tissue engineering in 1987 as “ an interdisciplinary field that applies the principles of engineering and the life sciences towards the development of biological substitutes that restore, maintain or improve tissue function” Tissue engineering • Potential advantages: – unlimited supply – no rejection issues – cost-effective Biopsy Human Cell Suspension Scaffold Nutrients, Growth Factors electrical chemical stimuli Bioreactorstimuli Implantation system operation mechanical stimuli H Scaffolds • A 3D substrate that is key component of tissue engineering • It needs to fulfil a number of requirement: - Controllably Porous structure - Interconnecting porosity - Appropriate surface chemistry - Appropriate mechanical properties - Biodegradable material - Tailorable Scaffolds Materials • Synthetic polymers: Aliphatic polyesters such as polyglycolic acid (PGA), polylactic acid ( PLLA), copolymers ( PLGA) and polycaprolactone ( PCL) are commonly used in tissue engineering. • Natural polymers: Most popular natural polymer used in tissue engineering is collagen. Synthetic polymers • More controllable from a compositional and materials processing viewpoint. • Scaffold architecture are widely recognized as important parameters when designing a scaffold • They may not be recognized by cells due to the absence of biological signals. Natural polymers • Natural materials are readily recognized by cells. • Interactions between cells and biological ECM are catalysts to many critical functions in tissues • These materials have poor mechanical properties. Cells Chen and Mooney Pharmaceutical Research, Vol. 20, No. 8, August 2003. Cells Growth factors Cumulative TGF-β1 release from chitosan microspheres. J.E. Lee et al. / Biomaterials 25 (2004) 4163–4173 [3H] thymidine uptake of chondrocytes encapsulated in collagen/chitosan/GAG scaffolds with and without TGF-β1 microspheres (S, S-TGF). Oxford Biomaterials group • Collagen • Rapid prototyping: 3D wax printer Why collagen? • It is the ideal scaffold material: is an important ECM molecule and is the major structural component in the body. posses ideal surface for cell attachment in the body. biocompatible and degrades into harmless products that are metabolized or excreted. a very poor antigen , non-toxic. Collagen processing • This technique allow the control over pore size and porosity. Dry collagen scaffold • Achieved through variation of freezing temperature and collagen dispersion concentration Indirect Solid Freeform fabrication (ISFF) Computer Aided Design 1 2 Jet Head Mill Dissolve away biosupport Negative mould Elevator AutoCAD design Scaffold Negative mould fabrication process Critical Point Drying Removal of BioBuild Freezing Collagen/HA at -30°C casting Collagen scaffold fabrication 3-D printing From Dr. Chaozong Liu Printing video Tissue engineering scaffold: controlled architecture Featured with: Pre-defined channels; with highly porous structured matrix; With suitable chemistry for tissue growth – Collagen or HA No toxic solvent involved, it offers a strong potential to integrate cells/growth factors with the scaffold fabrication process. From Dr. Terry Socholas Advantages of ISFF • Control of the external structure: Technology: CT/MRI CAD Heart valve tissue engineering Valve cells Collagen scaffold of heart valve Heart valve postimplantation Scaffolds with microchannels Design Aclian Blue staining revealed that extensive chondrogenesis were produced along the channels. Sirius Red staining revealed collagens production ( osteogenesis) in the periphery. SEM images of scaffolds with channels and open porosity. hMSCs seeded channelled collagen scaffold stained with Sirius Red and Alcian Blue Take home message • Biomaterials are materials interact with biological tissue • It’s a multi-disciplinary subject • Important application include – efficient drug delivery in the body – Development of artificial tissue replacement similar to the original for clinical use – By tracking elemental fluctuation archaeology information can be revealed