The use of mesenchymal stem cells in collagen-based scaffolds for tissue-engineered repair of tendons

Abstract

Tendon and ligament injuries are significant contributors to musculoskeletal injuries. Unfortunately, traditional methods of repair are not uniformly successful and can require revision surgery. Our research is focused on identifying appropriate animal injury models and using tissue-engineered constructs (TECs) from bone-marrow-derived mesenchymal stem cells and collagen scaffolds. Critical to this effort has been the development of functional tissue engineering (FTE). We first determine the in vivo mechanical environment acting on the tissue and then precondition the TECs in culture with aspects of these mechanical signals to improve repair outcome significantly. We describe here a detailed protocol for conducting several complete iterations around our FTE 'road map.' The in vitro portion, from bone marrow harvest to TEC collection, takes 54 d. The in vivo portion, from TEC implantation to limb harvest, takes 84 d. One complete loop around the tissue engineering road map, as presented here, takes 138 d to complete.

The past, present and future in scaffold-based tendon treatments

“…Advancements in engineering, chemistry and biology have made available numerous technologies that allow fabrication of hierarchical threedimensional scaffolds that closely imitate native tendon architectural features and mechanical properties, whilst enabling localised and sustained delivery of therapeutics [350]. Collagen sponges, for example, with or without aligned tracks and loaded with GAGs, growth factors and various cell populations have demonstrated enhanced cell motility and phenotype maintenance in vitro and increased collagen expression levels in small animal models [351][352][353][354][355]. However, such scaffold conformations cannot provide adequate mechanical resistance, in such a high mechanical demand environment [356].…”

Human iPSC-Derived Neural Crest Stem Cells Promote Tendon Repair in a Rat Patellar Tendon Window Defect Model

“…Under general anesthesia, a patellar tendon window defect was created as previously described. 25 Briefly, under sterile condition, after shaving the fur of both hindlimbs, skin and the soft tissue were dissected via a ventral longitudinal incision to expose patellar tendon; then, a standardized fullthickness window defect (1 · 4 mm, narrower than the width of the graft to make the graft fill the defect tightly) was created in the central part of the tendon without reaching the tendon-bone interface. In the experimental limb, the window defect was filled with fibrin gel with iPSC-NCSCs, while the contralateral limb was filled with fibrin gel alone to serve as control.…”

Effect of Implanting a Soft Tissue Autograft in a Central-Third Patellar Tendon Defect: Biomechanical and Histological Comparisons

“…Tissue processing has been described previously [24] but a brief protocol is outlined below. Fixed patella-PT-tibia samples were sectioned in the transverse plane to isolate a) the patella and proximal PT, b) the tendon mid-substance, and c) the tibia and distal PT.…”