Enhanced tissue regeneration potential of juvenile articular cartilage.

BACKGROUND: Articular cartilage undergoes substantial age-related changes in molecular composition, matrix structure, and mechanical properties. These age-related differences between juvenile and adult cartilage manifest themselves as markedly distinct potentials for tissue repair and regeneration. PURPOSE: To compare the biological properties and tissue regeneration capabilities of juvenile and adult bovine articular cartilage. STUDY DESIGN: Controlled laboratory study. METHODS: Articular cartilage harvested from juvenile (age, 4 months) and adult (age, 6-8 years) bovine femoral condyles was cultured for 4 weeks to monitor chondrocyte migration, glycosaminoglycan content conservation, and new tissue formation. The cartilage cell density and proliferative activity were also compared. Additionally, the effects of age-related changes on cartilage gene expression were analyzed using the Affymetrix GeneChip array. RESULTS: Compared with adult cartilage, juvenile bovine cartilage demonstrated a significantly greater cell density, higher cell proliferation rate, increased cell outgrowth, elevated glycosaminoglycan content, and enhanced matrix metallopeptidase 2 activity. During 4 weeks in culture, only juvenile cartilage was able to generate new cartilaginous tissues, which exhibited pronounced labeling for proteoglycan and type II collagen but not type I collagen. With over 19,000 genes analyzed, distinctive gene expression profiles were identified. The genes mostly involved in cartilage growth and expansion, such as COL2A1, COL9A1, MMP2, MMP14, and TGFB3, were upregulated in juvenile cartilage, whereas the genes primarily responsible for structural integrity, such as COMP, FN1, TIMP2, TIMP3, and BMP2, were upregulated in adult cartilage. CONCLUSION: As the first comprehensive comparison between juvenile and adult bovine articular cartilage at the tissue, cellular, and molecular levels, the results strongly suggest that juvenile cartilage possesses superior chondrogenic activity and enhanced regenerative potential over its adult counterpart. Additionally, the differential gene expression profiles of juvenile and adult cartilage suggest possible mechanisms underlying cartilage age-related changes in their regeneration capabilities, structural components, and biological properties. CLINICAL RELEVANCE: The results of this comparative study between juvenile and adult bovine articular cartilage suggest an enhanced regenerative potential of juvenile cartilage tissue in the restoration of damaged articular cartilage.

Metacarpophalangeal collateral ligament reconstruction using small intestinal submucosa in an equine model.

Xenogeneic porcine small intestinal submucosa (SIS) is a natural, biodegradable matrix that has been successfully used as a scaffold for repair of tissue defects. The goal of this study was to compare a collateral ligament transection surgically reconstructed with an anchored SIS ligament to a sham-operated control procedure for the correction of joint laxity using an equine model. Ten metacarpophalangeal joints from 10 horses had complete transection of the lateral collateral ligament. In 6 horses, the collateral ligament was reconstructed with a multilaminate strip of SIS anchored with screws into bone tunnels proximal and distal to the joint. The sham controls had similar screws, but no SIS placed. Clinical compatibility and effectiveness were evaluated with lameness, incisional quality, and joint range of motion, circumference and laxity. Ligament structure and strength was quantified with serial high resolution ultrasound, histology, and mechanical testing at 8 weeks. Surgical repair with SIS eliminated joint laxity at surgery. SIS-treated joints had significantly less laxity than sham treatment at 8 weeks (p < 0.001). SIS-treated ligaments demonstrated a progressive increase in repair tissue density and fiber alignment that by week 8 were significantly greater than sham-treated ligament (p < 0.03). SIS-repaired ligament tended to have greater peak stress to failure than sham-treatment (p < 0.07). Cellularity within the ligament repair tissue and inflammation within the bone tunnel was significantly greater in the SIS-treated limbs (p < 0.017). Within the first 8 weeks of healing, SIS implanted to reinforce collateral ligament injury was biocompatible in the joint environment, restored initial loss of joint stability, and accelerated early repair tissue quality. SIS ligament reconstruction might provide benefit to early ligament healing and assist early joint stability associated with ligament injury.