Abstract
Tendon healing is generally a time-consuming process and often leads to a functionally altered reparative tissue. Using degradable scaffolds for tendon reconstruction still remains a compromise in view of the required high mechanical strength of tendons. Regenerative approaches based on natural decellularized allo- or xenogenic tendon extracellular matrix (ECM) have recently started to attract interest. This ECM combines the advantages of its intrinsic mechanical competence with that of providing tenogenic stimuli for immigrating cells mediated, for example, by the growth factors and other mediators entrapped within the natural ECM. A major restriction for their therapeutic application is the mainly cell-associated immunogenicity of xenogenic or allogenic tissues and, in the case of allogenic tissues, also the risk of disease transmission. A survey of approaches for tendon reconstruction using cell-free tendon ECM is presented here, whereby the problems associated with the decellularization procedures, the success of various recellularization strategies, and the applicable cell types will be thoroughly discussed. Encouraging in vivo results using cell-free ECM, as, for instance, in rabbit models, have already been reported. However, in comparison to native tendon, cells remain mostly inhomogeneously distributed in the reseeded ECM and do not align. Hence, future work should focus on the optimization of tendon ECM decellularization and recolonization strategies to restore tendon functionality.
Highlights
Tendon injuries still remain an orthopedic challenge [1,2]
This review summarizes and critically discusses currently published results of experimental settings based on decellularized extracellular matrix (ECM) for tendon reconstruction
Both tendons and ligaments are bradytrophic and hypovascular tissues composed of a few cells which are embedded within an abundant ECM consisting of mostly parallel arranged dense collagen fiber bundles and a few elastic fibers [28]
Summary
Tendon injuries still remain an orthopedic challenge [1,2]. The time-consuming healing process extends over many months and usually leads to a reparative scar tissue [3,4] (Figure 1). Since tendon reconstruction requires highly stable scaffolds, the implantation of a natural ECM might provide a promising therapeutic strategy Decellularized tissues such as porcine intestinal submucosa [18]. For the treatment of rotator cuff tendon tears, xenogenic ECM derived from the human, bovine, equine or porcine dermis, intestinal submucosa or pericard, has already entered the clinical praxis [23±25] These therapeutic approaches do not require the seeding of the ECM with autologous cells before implantation. The use of a decellularized ACL-ECM instead of an autografted tendon could circumvent donor-site morbidity of autografting, it remains questionable whether decellularized ACLs are suitable for ACL reconstruction For this reason, it may be a promising approach to reconstruct damaged tendons using an allo- or xenogenic tendon ECM as a natural scaffold, reseeded with autologous human tenocytes or other more abundant or proliferative cell types that possess a tenogenic differentiation potential. Human Achilles tendon several weeks after rupture stained for HE (C1) and alcian blue
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