Background-The outcome of ACL reconstruction is variable and many patients have increased joint laxity postoperatively.

In this study, we hypothesize that supplementation of suture repair of the anterior cruciate ligament (ACL) with platelet-rich plasma (PRP) will improve the biomechanics of the repair. Six 30-kg pigs underwent bilateral suture repair of the ACL. One side was treated with suture repair alone, while the contralateral side was treated with suture repair augmented with PRP. After 14 weeks in vivo, anteriorposterior (AP) knee laxity and the tensile properties of the repaired ligament were measured. The addition of PRP to the suture repairs did not improve AP knee laxity at 308 (p ¼ 0.73) or 608 (p ¼ 0.65). It also did not improve the maximum tensile load (p ¼ 0.64) or linear stiffness (p ¼ 0.42) of the ACL repairs after 14 weeks in vivo. The model had 80% power to detect a 30% improvement of biomechanical properties with PRP; thus, we are confident that a clinically meaningful effect as a result of adding PRP is unlikely. Use of PRP alone to supplement suture repair of the ACL is ineffective in this animal model. ß

In large tears, even with double-row repair, the beneficial effects of PRP alone are insufficient to compensate the progressed tissue damage. The study data suggest that PRP may promote healing of small- and medium-sized tears to reduce retear rates. However, despite the substantial biological effect, at current cost, the use of PRP is not cost-effective in arthroscopic repair of small- and medium-sized tears.

There has been recent interest in the biologic stimulation of anterior cruciate ligament (ACL) healing. However, the effect of age on the ability of ligaments to heal has not yet been defined. In this study, we hypothesized that skeletal maturity would significantly affect the cellular and vascular repopulation rate of an ACL wound site. Skeletally Immature (open physes), Adolescent (closing physes), and Adult (closed physes) Yucatan minipigs underwent bilateral ACL transection and suture repair using a collagen-platelet composite. The response to repair was evaluated histologically at 1, 2, and 4 weeks. All three groups of animals had completely populated the ACL wound site with fibroblasts at 1 week. The Immature animals had a higher cellular density in the wound site than the Adult animals at weeks 2 and 4. Cells in the Immature ligament wounds were larger and more ovoid than in the Adult wounds. There were no significant differences in the vascular density in the wound site. Animal age had a significant effect on the density of cells populating the ACL wound site. Whether this observed cellular difference has an effect on the later biomechanical function of the repaired ACL requires further study. ß

Anterior cruciate ligament (ACL) injuries are an important clinical problem, particularly for adolescent patients. The effect of skeletal maturity on the potential for ACL healing is as yet unknown. In this study, we hypothesized that fibroblastic cells from the ACLs of skeletally immature animals would proliferate and migrate more quickly than cells from adolescent and adult animals. ACL tissue from skeletally immature, adolescent, and adult pigs and sheep were obtained and cells obtained using explant culture. Cell proliferation within a collagen-platelet scaffold was measured at days 2, 7, and 14 of culture using AM MTT assay. Cellular migration was measured at 4 and 24 h using a modified Boyden chamber assay, and cell outgrowth from the explants also measured at 1 week. ACL cells from skeletally immature animals had higher proliferation between 7 and 14 days (p < 0.01 for all comparisons) and higher migration potential at all time points in both species (p < 0.01 for all comparisons). ACL cells from skeletally immature animals have greater cellular proliferation and migration potential than cells from adolescent or adult animals. These experiments suggest that skeletal maturity may influence the biologic repair capacity of intrinsic ACL cells. ß

Collagen-platelet composites have recently been successfully used as scaffolds to stimulate anterior cruciate ligament (ACL) wound healing in large animal models. These materials are typically kept on ice until use to prevent premature gelation; however, with surgical use, placement of a cold solution then requires up to an hour while the solution comes to body temperature (at which point gelation occurs). Bringing the solution to a higher temperature before injection would likely decrease this intra-operative wait; however, the effects of this on composite performance are not known. The hypothesis tested here was that increasing the temperature of the gel at the time of injection would significantly decrease the time to gelation, but would not significantly alter the mechanical properties of the composite or its ability to support functional tissue repair. Primary outcome measures included the maximum elastic modulus (stiffness) of the composite in vitro and the in vivo yield load of an ACL transection treated with an injected collagen-platelet composite. In vitro findings were that injection temperatures over 308C resulted in a faster visco-elastic transition; however, the warmed composites had a 50% decrease in their maximum elastic modulus. In vivo studies found that warming the gels prior to injection also resulted in a decrease in the yield load of the healing ACL at 14 weeks. These studies suggest that increasing injection temperature of collagen-platelet composites results in a decrease in performance of the composite in vitro and in the strength of the healing ligament in vivo and this technique should be used only with great caution. Recent studies have shown the efficacy of using collagen-platelet composites (CPCs) to stimulate anterior cruciate ligament (ACL) healing after partial and complete transection in animal models.1-3 These composites are thought to serve as a scaffold in the ACL wound site, filling the gap between the ruptured ends of the ACL, releasing growth factors, and promoting cellular proliferation and migration into the scaffold. 2,3The use of collagen-based composites is not limited to ACL repair. Collagen composites have also been used in the development of tissue analogues including vasculature, 4 skin, 5 nerve, 6 and bone. 7Collagen composites typically undergo gelation via a visco-elastic transition when brought to 378C 8,9 by nucleation of collagen monomers forming branched cross-linked networks.10 Therefore, these solutions are typically stored at 48C until use to prevent premature network formation. As a result, when these cold solutions are placed into the wound site at 48C, it can take in excess of 60 min for complete gelation to occur.11 This extensive time requirement makes the use of these materials prohibitive in the clinical arena. Therefore, there has been much recent interest in a controlled heating of the gels to a temperature higher than 48C before placement in the wound site to lessen the gelation time and increase surgical efficiency.A reported that the...

Recently there has been a great deal of interest in the use of biomaterials to stimulate wound healing. This is largely due to their ability to centralize high concentrations of compounds known to promote wound healing at a needed location. Joints present a unique challenge to using scaffolds because of the presence of enzymes in synovial fluid which are known to degrade materials that would be stable in other parts of the body. The hypothesis of this study was that atelocollagen scaffolds would have greater resistance to enzymatic degradation than scaffolds made of gelatin, fibrin and whole blood. To test this hypothesis, collagen and fibrin-based scaffolds were placed in matrix metallopeptidase-1 (MMP-1), elastase, and plasmin solutions at physiologic concentrations, and the degradation of each scaffold was measured at varying time points. The atelocollagen scaffolds had a significantly greater resistance to degradation by MMP-1, elastase and plasmin over the fibrin based scaffolds. The results suggest that atelocollagen-based scaffolds may provide some protection against premature degradation by synovial fluid enzymes over fibrin-based matrices.

The formation of a provisional scaffold is essential in wound healing. However, for tissues inside of joints, this process is impeded by the synovial fluid environment and wound healing is significantly impaired as a result. Therefore, development of substitute provisional scaffolds which are effective in the intra-articular environment is of great interest. Collagen-platelet hydrogels have recently been found useful as substitute provisional scaffolding materials. In this study, our hypothesis was that increasing the collagen density in the hydrogel would result in physiologic changes that would be likely to affect their function as provisional scaffold substitutes. The primary functional outcome measures were modulus of the hydrogel, platelet activation, fibroblast proliferation, and scaffold retraction. Increased collagen density resulted in collagen-platelet hydrogels with a higher storage modulus. Platelet activation was not found to be dependent on the collagen density within the range tested. Increasing the collagen density had a suppressive effect on both fibroblast proliferation and scaffold retraction. These studies suggest that the collagen density may be able to significantly influence the function of collagen-platelet hydrogels used as substitute provisional scaffolds.