Repair of patellar tendon injuries using a cell–collagen composite

Abstract

Collagen gels were seeded with rabbit bone marrow-derived mesenchymal stem cells (MSCs) and contracted onto sutures at initial cell densities of I , 4, and 8 million cellslml. These MSC-collagen composites were then implanted into full thickness, full length, central defects created in the patellar tendons of the animals providing the cells. These autologous repairs were compared to natural repair of identical defects on the contralateral side. Biomechanical, histological, and morphometric analyses were performed on both repair tissue types at 6, 12, and 26 weeks after surgery. Repair tissues containing the MSC-collagen composites showed significantly higher maximum stresses and moduli than natural repair tissues at 12 and 26 weeks postsurgery. However, no significant differences were observed in any dimensional or mechanical properties of the repair tissues across seeding densities at each evaluation time. By 26 weeks, the repairs grafted with MSC-collagen composites were one-fourth of the maximum stress of the normal central portion of the patellar tendon with bone ends. The modulus and maximum stress of the repair tissues grafted with MSCLcollagen composites increased at significantly faster rates than did natural repairs over time. Unexpectedly, 28% of the MSC ~ collagen grafted tendons formed bone in the regenerating repair site. Except for increased repair tissue volume, no significant differences in cellular organization or histological appearance were observed between the natural repairs and MSC-collagen grafted repairs. Overall, these results show that surgically implanting tissue engineered MSC-collagen composites significantly improves the biomechanical properties of tendon repair tissues, although greater MSC concentrations produced no additional significant histological or biomechanical improvement.

Effects of age on the repair ability of mesenchymal stem cells in rabbit tendon

“…Third, the surgical models for the two studies were not exactly the same. The earlier study removed bone blocks to simulate graft harvest procedures for cruciate ligament reconstruction [3] whereas the model in the current study did not. However, repairing both soft tissue and bone would be expected to challenge the repair more than repairing just the soft tissue, unless the bone injury may have introduced additional MSCs from bone into the soft tissue wound site.…”

“…I). The rabbit patellar tendon was chosen to investigate the effects of MSC aging because of our extensive experience with this model system in studies of repair and in vivo force measurement [3,4,17,31]. Furthermore, the 4-year old age group represents a geriatric state in rabbits as evidenced by a 50% population mortality rate and has been used previously in other investigations into age-related effects on tendon and ligament [17, 43,59].…”

“…Differentiation along these cellular lineages depends on the interaction of local cues from surrounding cells and extracellular matrix as well as the genomic potential of the cells [13]. When harvested from bone marrow, MSCs can be selected through specific culture conditions [37] and isolated from other bone marrow cells without losing their multipotentiality [3,4,8,30,60].…”

“…Our laboratory and others have used bone marrow-derived MSCs for tendon repair in the adolescent or young skeletally mature animal [3,4,47,53,601. Compared to controls, MSC-based tendon repair biomechanics and histology are improved in the Achilles [47,60], patellar [3,4], and flexor tendon models [53]. Despite the advantages that MSCs provide in the young adult repair model, no studies exist investigating their use in geriatric animals.…”

The use of autologous platelet–leukocyte gels to enhance the healing process in surgery, a review

“…Furthermore, released platelet growth factors induce a proliferation of tendon cells and stimulate production of VEGF and hepatocyte growth factor, a potent antifibrotic agent. The latter may be of importance in reducing scar formation and fibrosis in newly reconstructed tendon tissue, which may lead to poor outcomes [29].…”