Massachusetts Institute of Technology Harvard Medical School Brigham and Women’s/Massachusetts General Hosp. VA Boston Healthcare System 2.79J/3.96J/BE.441/HST522J BIOMATERIALS FOR JOINT REGENERATION-I M. Spector, Ph.D. and I.V. Yannas, Ph.D. TISSUES COMPRISING JOINTS Permanent Regeneration Prosthesis Scaffold Bone Yes Yes Articular cartilage No Yes* Meniscus No Yes* Ligaments No Yes* Synovium No No * In the process of being developed WOUND HEALING Roots of Tissue Engineering Injury Inflammation (Vascularized tissue) Reparative Process Regeneration* Repair (Scar) CT: bone CT: cartilage Ep: epidermis Nerve Muscle: smooth Muscle: cardiac, skel. 4 Tissue Categories Connective Tissue Epithelium Nerve Muscle *spontaneous TISSUE ENGINEERING What is tissue engineering? ? Production of tissue in vitro by growing cells in porous, absorbable scaffolds (matrices). Why is tissue engineering necessary? ? Most tissues cannot regenerate when injured or diseased. ? Even tissues that can regenerate spontaneously may not completely do so in large defects (e.g., bone). ? Replacement of tissue with permanent implants is greatly limited. TISSUE ENGINEERING Problems with Tissue Engineering ? Most tissues cannot yet be produced by tissue engineering (i.e., in vitro). ? Implantation of tissues produced in vitro may not remodel in vivo and may not become integrated with (bonded to) host tissue in the body. Solution ? Use of implants to facilitate formation (regeneration) of tissue in vivo. – “Regenerative Medicine” – Scaffold-based regenerative medicine ISSUES RELATED TO PERFORMANCE OF BONE GRAFT SUBSTITUTE MATERIALS ? Incorporation of the graft into host bone (to stabilize the graft material) by bone formation on the surface of the graft material (osteoconduction). ? Modulus matching of the graft material to host bone to prevent stress shielding. ? Osteoclastic resorption of the graft (versus dissolution) may be important because osteoclasts release regulators of osteoblast function. Image removed due to copyright considerations. Migration of synthetic hydroxyapatite particles from the periodontal defect in which they were implanted. Defect in the Proximal Tibia Filled with Particles of Synthetic Hydroxyapatite, 1yr f-u Potential for breakdown of the overlying art. cart. due to high stiffness of the subchondral bone? Bone loss due to stress-shielding? Region of high density and stiffness (cannot be drilled or sawn) BONE GRAFTS AND GRAFT SUBSTITUTES Components Calcium Phosphate Bone of Bone Ceramics Autograft Mineral Alone Hydroxyapatite Allograft* (Anorganic (Including Sintered Xenograft Bone, Bio-Oss) Bone) Organic Matrix Tricalcium (Demineralized Phosphate Bone) Other Calcium Sulfate Calcium Carbonate * Works well; potential problems of transmission of disease and low grade immune reaction BONE MINERAL VERSUS SYNTHETIC HYDROXYAPATITE Synthetic Bone Mineral Calcium Phosphates Chemical Calcium-deficient Hydroxyapatite carbonate apatite Whitlockite (TCP) and other calcium phosphate phases Crystalline Small crystalline size; Large crystallites; noncrystalline phase high crystallinity Mechanical Lower strength; Dense; higher lower modulus strength; higher modulus DESIREABLE PROPERTIES OF A BONE GRAFT MATERIAL Strength 1 Modulus 2 Osteo- 3 Osteoclast mod./high near bone conduct. resorption Allograft Yes Yes Yes Yes Anorganic Bone No 4 Yes Yes Yes Synthetic HA Yes No Yes ? Calcium Sulfate No Yes ? ? Polymers No Yes No No 1 Important to prevent stress shielding 2 Bone forms on the surface of the material; important for the initial incorporation of the graft. 3 Important as osteoclasts release regulators of osteoblast function. 4 Material cannot be used for immediate load bearing support. COMPRESSIVE PROPERTIES Ultimate Modulus of Comp. Str. Elasticity (MPa) (GPa) Cortical Bone 140 - 200 14 - 20 Cancellous Bone 5 - 60 0.7 - 1.5 Synthetic HA 200 - 900 34 - 100 Bone Mineral 25 6 (anorganic bone) Bone Mineral; organic matter removed bone - Bio-Oss Image removed due to copyright considerations Image removed due to copyright considerations OsteoGraf Synthetic Hydroxyapatites OsteoGen Image removed due to copyright considerations Image removed due to copyright considerations V. Benezra Rosen, et al. Biomat. 2001;23:921-928 Bio-Oss; anorganic bovine bone Bio-Oss Syn. HA IR Spectroscopy Image removed due to copyright considerations Image removed due to copyright considerations X-ray Diffraction showing crystallinity Image removed due to copyright considerations Comparison of Natural Bone Mineral and Synthetic HA in a Rabbit Model Patella Patellar Ligament Site for Implantation Medial Collateral Ligament T. Orr, et al. Biomat. 2001;22:1953-1959 Guide Pins Retrieval Jig Trephine T. Orr, et al. Biomat. 2001;22:1953-1959 7 days Synthetic Hydroxyapatite Photos removed due to copyright considerations. Natural Bone Mineral Bio-Oss, 40 days Photos removed due to copyright considerations. Implantation Time, weeks T. Orr, et al. Biomat. 2001;22:1953-1959 0 200 400 600 800 1000 1200 1400 1600 6 26 Syn. HA Bone Mineral 0 5 10 15 20 25 30 35 6 26 Syn. HA Bone Mineral Anat. Cont. The strength of the site implanted with syn. HA is high but so to is the modulus (stiffness); bone mineral may provide adequate strength while having a near-normal modulus. Comp. Strength, MPa Modulus, MPa AC Bio-Oss Biopsy from ankle fusion patient 6 mo. Photos removed due to copyright considerations. BONE GRAFT MATERIALS ? Allograft bone remains a valuable substance for grafting; care must be taken with respect to the transmission of disease. ? Many off-the-shelf bone graft substitute materials are now available and should be of value for many applications. ? Need to be aware of how the increase in stiffness caused by certain materials will affect the surrounding tissues so that we do not cause greater problems than we are trying to solve.