Toward Engineering a Biological Joint Replacement

Abstract

Osteoarthritis is a major cause of disability and pain for patients in the United States. Treatments for this degenerative disease represent a significant challenge considering the poor regenerative capacity of adult articular cartilage. Tissue-engineering techniques have advanced over the last two decades such that cartilage-like tissue can be cultivated in the laboratory for implantation. Even so, major challenges remain for creating fully functional tissue. This review article overviews some of these challenges, including overcoming limitations in nutrient supply to cartilage, improving in vitro collagen production, improving integration of engineered cartilage with native tissue, and exploring the potential for engineering full articular surface replacements. Keywordsbiological joint replacement; cartilage; tissue-engineering; nutrient diffusion; collagen production Over 20% of the adults in the United States (25 years and above) have osteoarthritis (OA) of the hip or knee (>46 million Americans). 1 OA is ranked as one of the top three causes for disability and contributes more than $185 billion dollars a year in related medical costs. [2][3][4] More than 580,000 arthroplasty procedures are performed each year in the U.S. 5 While joint replacement generally succeeds in decreasing or eliminating pain and restoring joint function, the lifespan of prostheses are limited due to wear, loosening, infection, and fracture of the implant or surrounding bone. 6-9 Alternative treatments have not yet been successful in providing a viable long-term option for cartilage repair. For example, allografts are limited by donor tissue availability and graft viability, 10,11 while autografts are limited by the availability of healthy tissue and donor site morbidity. Bio-engineered repair strategies that circumvent these limitations, while preserving the natural function of the joint and using Copyright © 2012 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript a procedure less invasive than total joint arthroplasty, may be optimal for treating younger OA patients.Articular cartilage serves as the load-bearing material of joints and possesses excellent friction, lubrication, and wear characteristics. 12 Successful replacement of damaged or injured articular cartilage will hinge on the ability to recapitulate the mechanical and structural properties of the healthy native tissue before implantation. Over the past two decades, there has been a wide interest in developing functional engineered cartilage. To grow cartilage tissue, cells are cultured within a three-dimensional (3D) scaffold that provides an initial structure for the de novo tissue [13][14][15] ; alternatively, cells may be cultured using scaffold-less techniques. 16,17 For example, autologous chondrocyte implantation (ACI) is a cell-based strategy where cells are injected directly into focal lesions and covered with a periosteal flap 18,19 whereas CARTIPATCH 18 uses a 3D agarose hydrogel scaffold to prevent leakage of cells, stabilize t...