Injection temperature significantly affects in vitro and in vivo performance of collagen‐platelet scaffolds

Abstract

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...

Primary Repair of the Anterior Cruciate Ligament: A Systematic Review

“…[20][21][22][23] Furthermore, other studies stressed the importance of providing a suitable biological environment by adding a collagen matrix sponge [25][26][27][28][29] or PRP to stimulate healing. [30][31][32][33] The literature suggests a mutually inclusive relation between collagen matrix sponge and PRP.…”

“…In addition, histologic analysis showed significantly increased cellularity for the collagen-platelet composite (CPC)eaugmented repair compared with the non-augmented group. Palmer et al 28 looked at the effect of warming such a CPC on ACL properties after primary repair. In the 5 female Yorkshire pigs euthanized at 14 weeks after the procedure, the authors determined that increased warming of the CPC adversely affected the ultimate biomechanical properties of the repaired ligament.…”

“…In addition to mechanical augmentation, several groups have investigated the role of biologics in primary ACL repair including the use of a collagen scaffold [25][26][27][28][29] and platelet-rich plasma (PRP). [30][31][32][33] Fleming et al 25 reported that augmentation with a bovine collagen scaffold alone did not improve the biomechanical properties of a repaired porcine ACL.…”

Ligament-Derived Matrix Stimulates a Ligamentous Phenotype in Human Adipose-Derived Stem Cells

“…[19][20][21][22][23][24][25][26][27][28][29] Purified collagen gel in particular has been investigated extensively as a substrate or cell delivery substrate for repair of tendon and ligament defects and supports cell migration, proliferation, alignment, glycosaminoglycan and collagen synthesis, and increased expression of genes associated with tendon and ligament. [30][31][32][33][34][35][36][37][38][39][40][41][42] Further, there is growing evidence that native extracellular matrices may possess additional biological factors that can enhance cell growth and differentiation in the absence of exogenous growth factors. For example, extensive work by Urist in the 1960s led to the identification and subsequent clinical development of demineralized bone matrix as an osteoinductive agent, 43,44 and recently cartilage-derived extracellular matrix (ECM) was found to induce chondrogenesis in MSCs and ASCs.…”

Advances in Quantification of Meniscus Tensile Mechanics Including Nonlinearity, Yield, and Failure

“…Colloquially, it refers to the onset of decreasing stiffness with increasing strain (i.e., a proportional limit) or the onset of plastic strain. Quantitatively, yield has been defined as the point of first divergence from the linear region [43][44][45], the point at which the slope subjectively decreases [46,47], or the intersection of a line parallel to the linear region but offset by a certain strain or displacement [48][49][50]. Defining the yield point relative to the linear region poses the problem of how to identify the linear region of a curve which is nonlinear from beginning to end.…”