Tendon tissue engineering: An overview of biologics to promote tendon healing and repair

Abstract

Tendons are dense connective tissues with a hierarchical polarized structure that respond to and adapt to the transmission of muscle contraction forces to the skeleton, enabling motion and maintaining posture. Tendon injuries, also known as tendinopathies, are becoming more common as populations age and participation in sports/leisure activities increases. The tendon has a poor ability to self-heal and regenerate given its intrinsic, constrained vascular supply and exposure to frequent, severe loading. There is a lack of understanding of the underlying pathophysiology, and it is not surprising that disorder-targeted medicines have only been partially effective at best. Recent tissue engineering approaches have emerged as a potential tool to drive tendon regeneration and healing. In this review, we investigated the physiochemical factors involved in tendon ontogeny and discussed their potential application in vitro to reproduce functional and self-renewing tendon tissue. We sought to understand whether stem cells are capable of forming tendons, how they can be directed towards the tenogenic lineage, and how their growth is regulated and monitored during the entire differentiation path. Finally, we showed recent developments in tendon tissue engineering, specifically the use of mesenchymal stem cells (MSCs), which can differentiate into tendon cells, as well as the potential role of extracellular vesicles (EVs) in tendon regeneration and their potential for use in accelerating the healing response after injury.

New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

“…On the other hand, the perfect animal model for tendinopathy does not exist, and models should be carefully considered in light of the specific research question [98]. In line with this the animal model used in the present study would be inadequate for investigating the efficacy of orthobiologics that aim at stimulating tissue-resident cells such as platelet rich plasma (PRP) [99][100][101] or exosomes derived from cultured stem cells [102][103][104]. In this regard, a recent double-blinded, randomized controlled clinical trial concluded that injections of PRP might not be beneficial in non-operative treatment of rotator cuff disease [105,106].…”

Endotenon-Derived Type II Tendon Stem Cells Have Enhanced Proliferative and Tenogenic Potential

“…Tendons connect muscles to bones and enable movement or joint stabilization [39]. Lesions and inflammation can occur in tendons because of mechanical stress, aging, or genetic predisposition [7,40].…”

Tendon-associated gene expression precedes osteogenesis in mid-palatal suture establishment

“…The formation of a PNT could be guided by and/or instructive for the biomechanical nature of the palate, as tendons and ligaments are in other musculoskeletal sites (Liu et al, 2017). This concept underlies recent innovation in regenerative tendon therapy, which may be leveraged for craniofacial applications in mechanically loaded settings (Citro et al, 2023).…”