De novo generation in an in vivo rat model and biomechanical characterization of autologous transplants for ligament and tendon reconstruction

Abstract

BackgroundSurgical reconstruction of ligaments and tendons is frequently required in clinical practice. The commonly used autografts, allografts, or synthetic transplants present limitations in terms of availability, biocompatibility, cost, and mechanical properties that tissue bioengineering aims to overcome. It classically combines an exogenous extracellular matrix with cells, but this approach remains complex and expensive. Using a rat model, we tested a new bioengineering strategy for the in vivo and de novo generation of autologous grafts without the addition of extracellular matrix or cells, and analyzed their biomechanical and structural properties. MethodsA silicone perforated tubular implant (PTI) was designed and implanted in the spine of male Wistar rats to generate neo-transplants. The tensile load to failure, stiffness, Young modulus, and ultrastructure of the generated tissue were determined at 6 and 12weeks after surgery. The feasibility of using the transplant that was generated in the spine as an autograft for reconstruction of medial collateral ligaments (MCL) and Achilles tendons was also tested. FindingsUse of the PTI resulted in de novo transplant generation. Their median load to failure and Young modulus increased between 6 and 12weeks (respectively 12N vs 34N and 48MPa vs 178MPa). At 12weeks, the neo-transplants exhibited collagen bundles (mainly type III) parallel to their longitudinal axis and elongated fibroblasts. Six weeks after their transfer to replace the MCL or the Achilles tendon, the transplants were still present, with their ends healed at their insertion point. InterpretationThis animal study is a first step in the design and validation of a new bioengineering strategy to develop autologous transplants for ligament and tendon reconstructions.