Abstract
Tendons link muscle to bone and transfer forces necessary for normal movement. Tendon injuries can be debilitating and their intrinsic healing potential is limited. These challenges have motivated the development of model systems to study the factors that regulate tendon formation and tendon injury. Recent advances in understanding of embryonic and postnatal tendon formation have inspired approaches that aimed to mimic key aspects of tendon development. Model systems have also been developed to explore factors that regulate tendon injury and healing. We highlight current model systems that explore developmentally inspired cellular, mechanical, and biochemical factors in tendon formation and tenogenic stem cell differentiation. Next, we discuss in vivo, in vitro, ex vivo, and computational models of tendon injury that examine how mechanical loading and biochemical factors contribute to tendon pathologies and healing. These tendon development and injury models show promise for identifying the factors guiding tendon formation and tendon pathologies, and will ultimately improve regenerative tissue engineering strategies and clinical outcomes.
Highlights
Models of embryonic and postnatal tendon development Tendon formation is initiated in early development as the musculoskeletal and connective tissues differentiate from embryonic mesoderm [15]
E13 chick metatarsal tendon cells seeded into fibrin gels at ~ 1.5 million cells/mL and cultured for up to 42 days resulted in tissue constructs that appeared similar to embryonic tendon, with newly synthesized collagen fibrils aligned along the axis of tension [36]
This study further showed that TGFβ2 may be useful in tenogenic induction of mesenchymal stem cells (MSCs), and that cell-cell junctions found in embryonic tendon [28, 64], may be regulated during tenogenesis
Summary
Tendons transfer forces from muscle to bone and are essential for movement. tendons are frequently injured [1], and their poor healing ability results in long-term loss of function [2]. Medical interventions, including surgical and non-surgical treatments, physical therapy, steroid injections, and anti-inflammatory medications have limited efficacy, and re-rupture is common [3]. These poor outcomes motivate the search for alternative treatment strategies aimed at preventing tendon injury, improving regenerative healing, and developing engineered tendon tissue replacements from stem cells. A major challenge for developing regenerative approaches has been a limited understanding of the factors that regulate tendon formation, injury, and healing. Over the past 20 years, significant progress has been made in identifying underlying cellular, biochemical, and mechanical factors that regulate tendon formation during early development, and these important findings have been discussed in
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