A Bioengineered Organized Collagen-Based Microfibrous Implant Designed for Tendon Regeneration

Abstract

Category: Basic Sciences/Biologics; Sports Introduction/Purpose: Tendon healing is a slow and complicated process that results in inferior structural and functional properties compared to healthy tissue. It may be possible to improve outcomes of tendon healing with enhancement of biological repair through the development of tissue engineered medical products (TEMPs). Although many tendons heal with satisfactory outcomes, others do not, leading to pain and additional cost. Current augments for repair lack either native tissue structure or composition, limiting their potential effectiveness. For example, in tendon healing, restoring native organized and dense collagen composition is a primary goal; however, most TEMPs, such as lyophilized collagen or electrospun pure collagen fibers, are mechanically weak and unstable. For optimizing stability and biocompatibility, collagen can be combined with a high-performance co-biopolymer, such as poly(D,L-lactide) (PDLLA). Methods: The purpose of this study was to demonstrate the efficacy of a novel biointegrative construct, composed of type I collagen and PDLLA for Achilles tendon repair. PDLLA is biocompatible, has shown to support cell growth, and degrades to CO2 and H2O in vivo. The electrospun copolymer constructs were post-processed with low-temperature annealing to enhance their porosity and mechanical stability. The constructs were first tested for their ability to absorb blood and platelet-rich-plasma (PRP). Additionally, the constructs were tested in vivo by implantation in a rabbit Achilles tendon injury model by creating a 7 mm midsubstance Achilles defect. For each tendon defect, a copolymer construct was circumferentially wrapped around the defect and sutured into place. Finally, human cadaver testing was performed to assess implant handling and fixation characteristics. Results: Collagen-PDLLA constructs absorbed more than ten times their weight in blood and PRP. Histologically, rabbit tendons showed rapid implant cellularization by 2-8 weeks, along with de novo collagen deposition. By 16 weeks, dense collagenous connective tissue was seen integrating at the tendon-implant interface and throughout the implant. Movin-Bonar scores for the collagen-PDLLA-implanted and sham-operated tendons were identical from 16-72 weeks post-operatively, indicating a return to normal tendon morphology. Overall, surgical application of the collagen-PDLLA constructs demonstrated dense collagenous fibrous connective tissue ingrowth into and around the implant. Moreover, cadaver surgical implantation of the implant in a minimally invasive Achilles tendon repair and arthroscopic rotator cuff repair, allowed easy graft orientation and delivery as well as excellent handleability and suture fixation to the native tendon. Conclusion: Electrospun biointegrative implants were tissue-engineered to enhance cell infiltration for promoting tissue integration and functional remodeling. When implanted in the rabbit Achilles tendon, the implants demonstrated new in situ tissue generation and remodeled into dense, regularly oriented connective tissue at the tendon-implant interface. Collagenous ingrowth may be crucial in tendon protection and significantly progresses towards improving clinical outcomes following tendon injury. Moreover, the implants demonstrated additional clinical utility by absorbing greater than ten times their weight in biologic fluids which demonstrates the potential to combine this novel biointegrative implant with additional fluid based biologic therapies.