Hyaluronan‐based polymers in the treatment of osteochondral defects

Abstract

Summary: Articular cartilage in adults has limited ability for self-repair. Some methods devised to augment the natural healing response stimulate some regeneration, but the repair is often incomplete and lacks durability. Hyaluronan-based polymers were tested for their ability to enhance the natural healing response. It is hypothesized that hyaluronan-based polymers recreate an embryonic-like milieu where host progenitor cells can rcgcncrate the damaged articular surface and underlying bone. Oskochondral dcfccts were made on the femoral condyles of 4-month-old rabbits and were left empty or filled with hyaluronan-based polymers. The polymers tested were ACP sponge. made of crosslinked hyaluronan, and HYAFF-11 sponge, made of benxylated hyaluronan. The rabbits were killed 4 and 12 weeks after surgery, and the condyles were processed for histology. All 12-week defects were scored with a 29-point scale, and the scores were compared with a Kruskall-Wallis analysis of variance on ranks. Untreated defects filled with bone tissue up to or beyond the tidemark, and the noncalcified surface layer varied from fibrous to hyaline-like tissue. Four weeks aftcr surgery, defects treated with ACP exhibited bone filling to the level of the tidemark and the surface layer was composed of hyaline-like cartilage well integrated with the adjacent cartilage. At 12 weeks, the specimens had bone beyond the tidemark that was covered with a thin layer of hyaline cartilage. Four weeks after surgery, defects treated with HYAFF-11 contained a rim of chondrogcnic cells at the interface of the implant and the host tissue. In general, the 12-week dcfccts exhibited good bone fill and the surface was mainly hyaline cartilage. Treated defects received significantly higher scores than untreated defects (p < 0.05), and ACP-trcatcd defects scored significantly higher than HYAFF-11-treated defects (p < 0.05). The introduction of these hyaluronan-based polymers into delects provides an appropriate scaffolding and favorable microenvironnient for the reparative process. Further work is required to lully assess thc long-term outcome of defects treated with these polymers.The successful regeneration of any tissue requires not oiily reparative cells with the potential to differentiate into the phenotypes required to restore the damaged site but also a microenvironment that supports the proliferation and differentiation of those cells (12). It is our hypothesis that these reparative cells recapitulate, a t least in part. the sequence of events that leads to the formation of differentiated tissues during embryonic development; therefore. materials that mimic an embryonic environment may be superior scaffolds for tissue-engineered repair of damaged tissues.Articular cartilage has no vascular supply or easy access to large quantities of progenitor cells: thus, cartilage repair is often unsuccessful. Some studies indicate that full-thickness lesions in young animals are

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