Decellularized Tendon Extracellular Matrix—A Valuable Approach for Tendon Reconstruction?

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.

Role of tissue engineering in tendon reconstructive surgery and regenerative medicine: Current concepts, approaches and concerns

“…The classic tissue-engineered products are the allo-or xeno-geneic-based grafts that are processed only by acellularization technologies 15,16,51,52 . Thus, their architecture could not be re-designed in a more effective manner after implantation in the injured tendons 15 . Despite acellularization of such grafts, their rejection rate is high and therefore, they cannot be considered as tissue grafts 5,7 .…”

“…In addition, in vivo studies regarding the role of tissue-engineered products on regenerative medicine have not focused on mechanistic researches, and they have only observed the qualitative results with poor subjective data 5,6 . Therefore, there are many controversies between the results of the in vivo studies and there are also many differences between the sources, designing and preparation methods of the tissue-engineered grafts, which make their comparison hard to follow 5,7,15,16 . Regardless of the efficacy of these tissue-engineered products, there are some great concerns that should be addressed in future studies 13 .…”

“…Sterilization is another factor that should be addressed 2 . By removing all cellular and microbiological structures, the immune response could be reduced in order to increase the chance of graft incorporation in the healing process 15,33,34 . Increasing the number of specified molecules in the architecture of the scaffold could reduce the limitation of each molecule 15,59 .…”

Site-dependent acellularisation effects explain altered tissue mechanics: ultrastructural insights

“…These findings have a strong clinical implication. Acellular matrices have evolved becoming suitable scaffolds for soft tissue reconstruction [1,2,[5][6][7] due to their reduced antigenicity caused by the partial or complete absence of cellular proteins [9]. We could show previously that acellularisation-related effects are tissuedependent [8].…”

“…Being freed of cells and cellular components, these scaffolds produce minute antigenicity [2,6,9] and provide a biologic environment for cellular ingrowth and subsequent remodelling. However, there is a lack of morphologic and functional data on how exactly the commonly used methods of acellularisation impact extracellular matrix integrity, including commonly used chemical and physical protocols [3,10].…”