Effect of connective tissue growth factor delivered via porous sutures on the proliferative stage of intrasynovial tendon repair

Abstract

Recent growth factor, cell, and scaffold-based experimental interventions for intrasynovial flexor tendon repair have demonstrated therapeutic potential in rodent models. However, these approaches have not achieved consistent functional improvements in large animal trials due to deleterious inflammatory reactions to delivery materials and insufficient induction of targeted biological healing responses. In this study, we achieved porous suture-based sustained delivery of connective tissue growth factor (CTGF) into flexor tendons in a clinically relevant canine model. Repairs with CTGF-laden sutures were mechanically competent and did not show any evidence of adhesions or other negative inflammatory reactions based on histology, gene expression, or proteomics analyses at 14 days following repair. CTGF-laden sutures induced local cellular infiltration and a significant biological response immediately adjacent to the suture, including histological signs of angiogenesis and collagen deposition. There were no evident widespread biological effects throughout the tendon substance. There were significant differences in gene expression of the macrophage marker CD163 and anti-apoptotic factor BCL2L1; however, these differences were not corroborated by proteomics analysis. In summary, this study provided encouraging evidence of sustained delivery of biologically active CTGF from porous sutures without signs of a negative inflammatory reaction. With the development of a safe and effective method for generating a positive local biological response, future studies can explore additional methods for enhancing intrasynovial tendon repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2052-2063, 2018.

The cellular basis of fibrotic tendon healing: challenges and opportunities

“…Canine models been used to demonstrate that early, active mobilization following repair reduced the formation of peritendinous adhesions and improved the ultimate strength of injured compared to immobilization following flexor tendon injury (19,20). The canine flexor tendon repair model has also been used to identify improved suture techniques (21,22) and evaluate various biologics for tendon repair (23,24). Rodent models, most notably mouse and rat, have been used to study the healing process in various tendons following injury both with and without surgical repair.…”

Tendon and multiomics: advantages, advances, and opportunities

“…Other studies 104 have used proteomics to look for inflammatory pathway upregulation as a means of identifying potential safety problems with engineered approaches that could impair in vivo repair. Delivery of connective tissue growth factor ( CTGF) through sutures in a canine flexor tendon injury model found no difference in inflammatory protein levels compared to sutures without CTGF 104 , suggesting that CTGF is not pro-inflammatory or detrimental when incorporated into engineered strategies in vivo.…”

Effectiveness of Hyaluronan Autocross-Linked-Based Gel in the Prevention of Peritendinous Adherence Following Tenolysis

“…Different in vitro models have been used, including animals (dog, chicken, rabbit, rat, and horse) [21][22][23]45], tendons [46,47], and procedures of induced tendon damage (surgical, collagenase, or steroid lesion). So far, numerous studies have evaluated in vitro responses in animal models regarding the effect of various growth factors or the impact of the same growth factor inhibitors to monitor the healing process and acquire adhesion-free tendons [48][49][50][51][52]. Nevertheless, a limited number of pre-clinical studies have led to clinical trials, and to date, no favorable clinical outcomes have been obtained regarding adhesion reduction, although some adhesion barriers have demonstrated satisfactory clinical efficacy.…”