Massachusetts Institute of Technology VE RII! TAS Harvard medical school Brigham and Womens/Massachusetts General Hosp VA Boston Healthcare System 279J396J/BE441/HST522J BIOMATERIALS FOR JOINT REGENERATION-I M. Spector, Ph D and I.v. Yannas, Ph. D
Massachusetts In Massachusetts Institute of Technology stitute of Technology Harvard Medical School Harvard Medical School Brigham and Wo Brigham and Women’s/Massachusetts General Hosp. men’s/Massachusetts General Hosp. VA Boston Healthcare System VA Boston Healthcare System 2.79J/3.96J/BE.441/HST522J 2.79J/3.96J/BE.441/HST522J BIOMATERIALS FOR JOINT BIOMATERIALS FOR JOINT REGENERATION REGENERATION-I M. Spector, Ph.D. and I.V. Yannas, Ph.D. M. Spector, Ph.D. and I.V. Yannas, Ph.D
TISSUES COMPRISING JOINTS Permanent Regeneration Prosthesis Scaffold Bone Yes Yes Articular cartilage 0 Yes* Meniscus 0 Yes x Ligaments No Yes i Synovium No No s In the process of being developed
TISSUES COMPRISING JOINTS TISSUES COMPRISING JOINTS Permanent Permanent Regeneration Regeneration Prosthesis Prosthesis Scaffold Scaffold Bone Yes Yes Articular cartilage Articular cartilage No Yes* Meniscus Meniscus No Yes* Ligaments Ligaments No Yes* Synovium Synovium No No * In the process of being developed * In the process of being developed
WOUND HEALING Roots of Tissue Engineering Insur 4 Tissue categories Connective Tissue Inflammation Epithelium (Vascularized tissue Nerve Muscle Reparative P rocess R egeneration Repair(scar) cT bone CT: cartilage Ep: epidermis erve Muscle: smooth Muscle: cardiac skel spontaneous
WOUND HEALING WOUND HEALING Roots of Tissue Engineering Roots of Tissue Engineering Injury Inflammation Inflammation (Vascularized tissue) (Vascularized tissue) Reparative Reparative Process Process Regeneration* Regeneration* Repair (Scar) Repair (Scar) CT: bone CT: bone CT: cartilage CT: cartilage Ep: epidermis : epidermis Nerve Muscle: smooth Muscle: smooth Muscle: cardiac, Muscle: cardiac, skel . 4 Tissu 4 Tissu e Categories Categories Connective Tissue nnective Tissue Epithelium Epithelium Nerve Muscle *spontaneous *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(eg, bone). Replacement of tissue with permanent implants is greatly limited
TISSUE ENGINEERING TISSUE ENGINEERING What is tissue engineering? What is tissue engineering? • Production of tissue Production of tissue in vitro in vitro by growing cells by growing cells in porous, absorbable scaffolds (matrices). in porous, absorbable scaffolds (matrices). Why is tissue engineering necessary? Why is tissue engineering necessary? • Most tissues cannot regenerate when Most tissues cannot regenerate when injured or diseased. injured or diseased. • Even tissues that can regenerate Even tissues that can regenerate spontaneously may not completely do so in spontaneously may not completely do so in large defects ( large defects (e.g., bone). ., bone). • Replacement of tissue with permanent Replacement of tissue with permanent implants is greatly limited. implants is greatly limited
TISSUE ENGINEERING Problems with tissue engineering Most tissues cannot yet be produced by tissue engineering (ie, 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
TISSUE ENGINEERING TISSUE ENGINEERING Problems with Tissue Engineering Problems with Tissue Engineering • Most tissues cannot yet be produced by Most tissues cannot yet be produced by tissue engineering ( tissue engineering (i.e., in vitro in vitro). • Implantation of tissues produced Implantation of tissues produced in vitro in vitro may not remodel may not remodel in vivo in vivo and may not and may not become integrated with (bonded to) host become integrated with (bonded to) host tissue in the body. tissue in the body. Solution Solution • Use of implants to facilitate formation Use of implants to facilitate formation (regeneration) of tissue (regeneration) of tissue in vivo. in vivo. – “Regenerative Medicine” “Regenerative Medicine” – Scaffold Scaffold -based regenerative medicine 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
ISSUES RELATED TO PERFORMANCE OF ISSUES RELATED TO PERFORMANCE OF BONE GRAFT SUBSTITUTE MATERIALS BONE GRAFT SUBSTITUTE MATERIALS • Incorporation of the graft into host bone (to Incorporation of the graft into host bone (to stabilize the graft material) by bone formation stabilize the graft material) by bone formation on the surface of the graft material on the surface of the graft material (osteoconduction osteoconduction). • Modulus matching of the graft material to host Modulus matching of the graft material to host bone to prevent stress shielding. bone to prevent stress shielding. • Osteoclastic Osteoclastic resorption of the graft (versus resorption of the graft (versus dissolution) may be important because dissolution) may be important because osteoclasts osteoclasts release regulators of osteoblast release regulators of osteoblast function. function
Image removed due to copyright considerations Migration of synthetic hydroxyapatite particles from the periodontal defect in which they were implanted
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, lyr f-u Potential for breakdown of the overlying art. cart due to high stiffness of the subchondral bone Region of high Bone loss due to density and stress-shielding? stiffness (cannot be drilled or sawn)
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 B one of Bone Ceramics Autograft Mineral Alone Hydroxyapatite Allografts (Anorganic (Including Sintered Xenograft Bone, Bio-Oss Bone) Organic matrix Tricalcium (Demineralized Phosphate Bone Other Calcium Sulfate Works well; potential problems of transmission of disease and Calcium Carbonate low grade immune reaction
BONE GRAFTS AND GRAFT SUBSTITUTES BONE GRAFTS AND GRAFT SUBSTITUTES Components Components Calcium Phosphate Calcium Phosphate Bone of Bone of Bone Ceramics Ceramics Autograft Autograft Mineral Alone Mineral Alone Hydroxyapatite Hydroxyapatite Allograft* Allograft* (Anorganic (Anorganic (Including Sintered (Including Sintered Xenograft Xenograft Bone, Bio Bone, Bio -Oss) Bone) Organic Matrix Organic Matrix Tricalcium Tricalcium (Demineralized (Demineralized Phosphate Phosphate Bone) Other Calcium Sulfate Calcium Sulfate Calcium Carbonate Calcium Carbonate * Works well; Works well; potential problems potential problems of transm of transmission of disease and ission of disease and low grade im low grade immune reaction mune 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
BONE MINERAL VERSUS BONE MINERAL VERSUS SYNTHETIC HYDROXYAPATITE SYNTHETIC HYDROXYAPATITE Synthetic Synthetic Bone Mineral Bone Mineral Calcium Phosphates Calcium Phosphates Chemical Chemical Calcium Calcium -deficient deficient Hydroxyapatite Hydroxyapatite carbonate apatite carbonate apatite Whitlockite Whitlockite (TCP) and other calcium and other calcium phosphate phases phosphate phases Crystalline Crystalline Small crystalline size; Small crystalline size; Large crystallites; Large crystallites; noncrystalline phase noncrystalline phase high crystallinity high crystallinity Mechanical Mechanical Lower strength; Lower strength; Dense; higher Dense; higher lower modulus lower modulus strength; strength; higher modulus higher modulus