Tissue‐engineered composites for the repair of large osteochondral defects

Abstract

Objective. To test the hypothesis that engineered cartilage can provide a mechanically functional template capable of undergoing orderly remodeling during the repair of large osteochondral defects in adult rabbits, as assessed by quantitative structural and functional methods.Methods. Engineered cartilage generated in vitro from chondrocytes cultured on a biodegradable scaffold was sutured to a subchondral support and the resulting composite press-fitted into a 7-mm long, 5-mm wide, 5-mm deep osteochondral defect in a rabbit knee joint. Defects left empty (group 1) or treated with cell-free composites (group 2) served as controls for defects treated with composites of engineered cartilage and the support, without or with adsorbed bone marrow (groups 3 and 4, respectively).Results. Engineered cartilage withstood physiologic loading and remodeled over 6 months into osteochondral tissue with characteristic architectural features and physiologic Young's moduli. Composites integrated well with host bone in 90% of cases but did not integrate well with host cartilage. Structurally, 6-month repairs in groups 3 and 4 were superior to those in group 2 with respect to histologic score, cartilage thickness, and thickness uniformity, but were inferior to those in unoperated control tissue. At 6 months, Young's moduli in groups 2, 3, and 4 (0.68, 0.80, and 0.79 MPa, respectively) approached that in unoperated control tissue (0.84 MPa), whereas the corresponding modulus in group 1 (0.37 MPa) was significantly lower.Conclusion. Composites of tissue-engineered cartilage and a subchondral support promote the orderly remodeling of large osteochondral defects in adult rabbits.Various techniques for the repair of fullthickness articular cartilage lesions are under investigation, reflecting the well-known problem that damaged adult articular cartilage has limited healing capacity (1,2). Large osteochondral defects are associated with mechanical instability and are accepted indications for surgical intervention to prevent development of degenerative joint disease (3,4). Ideally, a large osteochondral defect should be repaired with a graft that can provide mechanical stability and allow early postoperative function under physiologic loading conditions. These requirements potentially can be met using engineered cartilage (5).In the present study, we tested the hypothesis that engineered cartilage can provide a mechanically functional template capable of undergoing orderly remodeling and permit the repair of large osteochondral defects in adult rabbits, as assessed by quantitative structural and functional methods. Engineered cartilage generated in vitro from chondrocytes cultured on a biodegradable scaffold (6) was sutured to a subchondral support and the resulting composite, with or without adsorbed bone marrow, was press-fit into a surgically created femoropatellar groove defect (Figure 1). Defects that were left empty, defects that were treated with cell-free composites of the scaffold and the support, and native tissues from unopera...

A biomimetic multi-layered collagen-based scaffold for osteochondral repair

“…This is done in an effort to provide an environment that can support the existing host cell population thereby circumventing the costly and cumbersome requirement of in vitro pre-culture prior to implantation. Numerous scaffolds utilised in this area consist of synthetic materials, such as poly(e-caprolactone) (PCL) [12], poly(glycolic acid) (PGA) [13] and poly(lactide-co-glycolide) (PLGA) [14,15].…”

“…However, slow degradation rates, harmful degradation by-products, poor cell attachment, inability to direct cellular differentiation, and reduced immunogenicity have led to limited long-term success following in vivo application [13]. Natural materials, including collagen [16,17] fibrin [18], hyaluronan [19], alginate [20] and agarose [21][22][23], have been widely investigated for use in osteochondral tissue repair.…”

Engineering osteochondral constructs through spatial regulation of endochondral ossification

“…Damage to the articular surface can penetrate to the subchondral bone and such osteochondral defects are often associated with mechanical instability of the joint and warrant surgical intervention in order to prevent osteoarthritic degenerative changes [1]. Even in cases where lesions do not penetrate to the subchondral bone an osteochondral construct may be a more desirable implant as a bone-to-bone interface integrates better than a cartilage-to-cartilage interface [2].…”

Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model

“…A number of studies performed in rabbit (Ball et al, 2004;Grigolo et al, 2001;Schaefer et al, 2002), sheep (Kandel et al, 2006), or goat (Niederauer et al, 2000) aimed at investigating the outcome of cartilage or osteochondral repair using engineered cartilage. Cells were seeded in the scaffolds either directly after isolation or after an expansion phase and further pre-cultured in vitro for 48 h (Niederauer et al, 2000), 7 d (Ball et al, 2004), 4 to 6 weeks (Schaefer et al, 2002), or 8 weeks (Kandel et al, 2006) before implantation in an orthotopic site. With only one exception (Niederauer et al, 2000), an improved healing was observed when cells were added to the scaffolds as compared to implantation of cell-free materials.…”