Decellularized and Engineered Tendons as Biological Substitutes: A Critical Review

Abstract

Tendon ruptures are a great burden in clinics. Finding a proper graft material as a substitute for tendon repair is one of the main challenges in orthopaedics, for which the requirement of a biological scaffold would be different for each clinical application. Among biological scaffolds, the use of decellularized tendon-derived matrix increasingly represents an interesting approach to treat tendon ruptures. We analyzed in vitro and in vivo studies focused on the development of efficient protocols for the decellularization and for the cell reseeding of the tendon matrix to obtain medical devices for tendon substitution. Our review considered also the proper tendon source and preclinical animal models with the aim of entering into clinical trials. The results highlight a wide panorama in terms of allogenic or xenogeneic tendon sources, specimen dimensions, physical or chemical decellularization techniques, and the cell type variety for reseeding from terminally differentiated to undifferentiated mesenchymal stem cells and their static or dynamic culture employed to generate implantable constructs tested in different animal models. We try to identify the most efficient approach to achieve an optimal biological scaffold for biomechanics and intrinsic properties, resembling the native tendon and being applicable in clinics in the near future, with particular attention to the Achilles tendon substitution.

Figure 1

Cumulative number of publications over years. Publication trend from January 2000 until April 2015 on studies performing both in vitro and in vivo tendon tissue decellularization.

Figure 2

Research strategy. Flow chart of selection process.

Figure 3

Tendon sources. The pie chart shows the relative distribution of species from which tendons have been harvested to be decellularized.

Figure 4

Reagents and detergents. The pie chart shows the percentage of physical, chemical, enzymatic, or associated detergents employed for tendon decellularization.

Figure 5

Cell sources. The pie chart shows the relative distribution of cell sources used to reseed the decellularized matrix.

Figure 6

Construct analyses. The pie chart shows the relative distribution of analyses performed to assess the quality of the decellularization and reseeding of the tendon matrix.