Boosting tendon repair: interplay of cells, growth factors and scaffold-free and gel-based carriers

Abstract

Background: Tendons are dense connective tissues and critical components for the integrity and function of the musculoskeletal system. Tendons connect bone to muscle and transmit forces on which locomotion entirely depends. Due to trauma, overuse and age-related degeneration, many people suffer from acute or chronic tendon injuries. Owing to their hypovascularity and hypocellularity, tendinopathies remain a substantial challenge for both clinicians and researchers. Surgical treatment includes suture or transplantation of autograft, allograft or xenograft, and these serve as the most common technique for rescuing tendon injuries. However, the therapeutic efficacies are limited by drawbacks including inevitable donor site morbidity, poor graft integration, adhesion formations and high rates of recurrent tearing. This review summarizes the literature of the past 10 y concerning scaffold-free and gel-based approaches for treating tendon injuries, with emphasis on specific advantages of such modes of application, as well as the obtained results regarding in vitro and in vivo tenogenesis.

Results: The search was focused on publications released after 2006 and 83 articles have been analysed. The main results are summarizing and discussing the clear advantages of scaffold-free and hydrogels carriers that can be functionalized with cells alone or in combination with growth factors.

Conclusion: The improved understanding of tissue resident adult stem cells has made a significant progress in recent years as well as strategies to steer their fate toward tendon lineage, with the help of growth factors, have been identified. The field of tendon tissue engineering is exploring diverse models spanning from hard scaffolds to gel-based and scaffold-free approaches seeking easier cell delivery and integration in the site of injury. Still, the field needs to consider a multifactorial approach that is based on the combination and fine-tuning of chemical and biomechanical stimuli. Taken together, tendon tissue engineering has now excellent foundations and enters the period of precision and translation to models with clinical relevance on which better treatment options of tendon injuries can be shaped up.

Keywords: Adipose-derived mesenchymal stem cells; Bone marrow-derived mesenchymal stem cells; Cell sheets; Hydrogels; Scaffold-free carriers; Scaffolds; Tendon repair; Tendon stem progenitor cells; Tendon tissue engineering; Tendons.

Fig. 1

Summary of the key components of tendon tissue engineering. a Favourable cell types; b Pro-tenogenic growth factors; c Possible scaffolds and self-assembled materials. Various combinations between the components are possible

Fig. 2

Flow chart of the search strategy and article selection in this review

Fig. 3

Cartoon of the procedure to form tendon-like cell sheet. a MSCs are plated in cell culture dish; b Cell monolayers are formed; c and d The monolayer is scraped out from dish surface and rolled up into a cell sheet; e and f The three-dimensional cell sheet is cultivated under static tension and let to mature prior transplantation in vivo