麻省理工大学：《生物材料——组织交互作用》教学讲义（英文版）BIOMATERIALS FOR JOINT REGENERATION-II

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-II 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-II 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

INTRAARTICULAR JOINT TISSUES What are the unique characteristics of the ioint environmen Why dont these tissues heal? How are such diverse functions met by only one structural protein- collagen

INTRAARTICULAR JOINT TISSUES INTRAARTICULAR JOINT TISSUES • What are the unique characteristics of What are the unique characteristics of the joint environment? the joint environment? • Why don’t these tissues heal? Why don’t these tissues heal? • How are such diverse functions met by How are such diverse functions met by only one structural protein only one structural protein - collagen? collagen?

INTRAARTICULAR ENVIRONMENT Synovial fluid High mechanical loads Low vascularity

INTRAARTICULAR INTRAARTICULAR ENVIRONMENT ENVIRONMENT • Synovial fluid Synovial fluid • High mechanical loads High mechanical loads • Low vascularity Low vascularity

JOINT TISSUES Limitations to Healing Absence of a fibrin clot Absent or low vascularity Dissolution of clot in synovial fluid Cell migration restricted by matrix ° Low cell density Low mitotic activit Mechanical loading disrupts reparative tissue

JOINT TISSUES JOINT TISSUES Limitations to Healing Limitations to Healing • Absence of a fibrin clot Absence of a fibrin clot –Absent or low vascularity Absent or low vascularity –Dissolution of clot in synovial Dissolution of clot in synovial fluid • Cell migration restricted by matrix Cell migration restricted by matrix • Low cell density Low cell density • Low mitotic activity Low mitotic activity • Mechanical loading disrupts Mechanical loading disrupts reparative tissue reparative tissue

JOINT TISSUES REPARATIVE PROCEDURES Art. cart. Microfracture, osteochondral plugS, articular chondrocyte implantation Tiss, engr. cart; Collagen matrices ACL Tendon autografts Meniscus Suture, meniscal allografts Collagen matrices

JOINT TISSUES JOINT TISSUES REPARATIVE PROCEDURES REPARATIVE PROCEDURES Art. Cart. Art. Cart. Microfracture, osteochondral Microfracture, osteochondral plugs, articular chondrocyte articular chondrocyte implantation implantation [Tiss. engr. cart.; . cart.; Collagen matrices] Collagen matrices] ACL Tendon autografts Tendon autografts Meniscus Meniscus Suture, meniscal allografts Suture, meniscal allografts [Collagen matrices] [Collagen matrices]

JOINT TISSUES Tissue Cell round/ Loading Type Type Lac. Coll. PG Vasc Heal. Art. Cart, Comp. Hyal Chond. Yes II ++ 0 0 Cart Meniscus C/T Fibro-Fibro- Yes I 0/+ 0* 0 Cart. chond ACL Tens. fibrous fibro- no 000 Tissue blast 兴 Inner third 兴Mid- substance

JOINT TISSUES JOINT TISSUES Tissue Cell Round/ Loading Loading Type Type Lac. Coll. PG Vasc .Heal. Art. Cart. Art. Cart.Comp. Hyal . Chond .Yes II +++ 0 0 Cart. Meniscus Meniscus C/T Fibro - Fibro - Yes I 0/+ 0* 0 Cart. Chond . ACL Tens. Fibrous Fibrous Fibro - No I 0 0** 0 Tissue blast * Inner third * Inner third ** Mid ** Mid -substance substance

ARTICULAR CARTILAGE Chondrocytes Extracellular matrix ater 66-78% Organic material 22-34 Proteoglycan 22-38% collagen type II 48-62 Fibronectin Other matrix proteins 05-15%

ARTICULAR CARTILAGE ARTICULAR CARTILAGE Chondrocytes Chondrocytes Extracellular matrix Extracellular matrix Water 66 -78% Organic material Organic material 22 -34% Proteoglycan Proteoglycan 22 -38% Collagen type II Collagen type II 48 -62% Fibronectin & Fibronectin & Other matrix proteins Other matrix proteins 05 -15%

Human Knee from Patient with rheumatoid Arthritis Image removed due to copyright considerations

Human Knee from Knee from Patient with Patient with Rheumatoid Rheumatoid Arthritis Arthritis Image removed due to copyright considerations

Arthroscopic Microfracture” Debridement Image removed due Image removed due to copyright to copyright considerations considerations Osteochondral plug Autograft (“ Mosaicplasty”) 30 years Image source: OCW Current clinical Practice Image removed due to copyright Image removed due considerations to copyright considerations Total K Replacement Autologous chondrocytes injected under a periosteal fla ap(Genzyme; Carticel")

Arthroscopic Debridement “Microfracture” Total Knee Replacement Current Clinical Practice Image removed due to copyright considerations Image removed due to copyright considerations Image removed due to copyright considerations Image removed due to copyright considerations Osteochondral Plug Autograft (“Mosaicplasty”) Autologous chondrocytes injected under a periosteal flap (Genzyme; “Carticel”) Total Knee Replacement 30 years Image source: OCW