PhD Student Chinese University of Hong Kong, Hong Kong
Abstract: Tendon injuries, caused by overuse or age-related degeneration, are a prevalent clinical problem The slow healing process of tendons is attributed to insufficient cellularity and vascularity, often leading to the formation of fibrotic scarring and adhesion. To date, mesenchymal stem cells (MSCs) have emerged as a promising candidate for tendon regeneration and repair; however, the clinical application of MSC-based therapies is impeded by obstacles such as acute cell death, low functional engraftment yields, and off-target tissue formation. To address these challenges, there is a need to develop strategies that can precisely induce MSCs tendon-specific differentiation within a biomimetic microenvironment prior to implantation.
In this study, we aimed to develop a hydrogel (TenoGel) that is biochemically and biomechanically co-stimulated to establish a functional tenogenic niche for stem cell pre-conditioning and delivery. The efficacy of TenoGel in promoting tendon healing was evaluated through two approaches: (1) In vitro characterization, which involved evaluating the effects of human adipose-derived stem cells (ASCs) tenogenic differentiation via established tenogenic markers. (2) In vivo evaluation using a rat patellar window defect model to examine tendon healing outcomes.
Our results indicate that TenoGel has high toughness and supports human ASCs with strong viability, early spreading, and rapid proliferation. When stimulated by tendon-specific factors and tensile loading, ASCs displayed an organized cytoskeletal structure and increased tenogenic marker expression. In a rat patellar tendon defect model, TenoGel combined with rat ASCs enhanced tendon regeneration, showing a wavy, organized matrix and improved biomechanical properties similar to the uninjured control group. These findings suggest that bioactive TenoGel could be a promising strategy for pre-conditioning and delivering stem cells to improve tendon repair, with further research planned on biomaterial-stem cell interactions using bioinformatics analysis.
TenoGel exhibited strong mechanical properties, high viability, and rapid spreading of ASCs. It also enhanced tenogenic differentiation of ASCs, enabling precise and functional tendon healing when combined with preconditioned rat ASCs in a rat model.
Funding Source: Research Grants Council of Hong Kong (GRF14118620; 14121121, DMW) National Natural Science Foundation of China/Research Grants Council of Hong Kong (N_CUHK409/23, DMW) Innovation and Technology Commission (Health@InnoHK, DMW)
