Rotator cuff repair in vivo with scaffolds, cells and/or growth factors

Background: Rotator cuff tears are very common and failure of the repair is still a problem. There are many new techniques that are currently being investigated in animal models in order to improve the outcomes of tendon repair but no systematic review has been accomplished to date. Objectives: To review the literature concerning the materials, cells and growth factors that are available for rotator cuff repair in vivo on animal models. This will allow the evaluation of the advantages and disadvantages of the different techniques. Data sources: We performed a systematic review using Medline, Embase and Cochrane Library electronic databases from inception of the database to September 16th 2015. Search terms included ‘rotator cuff’, ‘scaffold’, ‘biomaterial’, ‘tissue engineering’, ‘cell therapy’, ‘platelet-rich plasma’, ‘growth factor’. The bibliography of each selected article was hand searched for potential further useful references that could have been missed during this process. Study selection: Only studies focusing on in vivo animal models were considered and our focus was on histological and biomechanical outcomes. References that were only abstracts were rejected. Results: A total of 77 articles were included in the review. The supraspinatus tendon of the rat is the most commonly used model followed by the infraspinatus tendon of sheep, rabbits and dogs. Small intestine submucosa (SIS) and acellular dermal matrix (ADM) scaffolds are commonly used for tendon replacement or repair reinforcement with fairly good outcomes. Matrices with continuous mineralized-demineralized transition and scaffolds made of chitin/chitosan are also promising. As for synthetic scaffolds, derivatives of polylactic acid (PLA) and polyglycolic acid (PGA) showed the best outcomes and further association of gelatin with them was shown to be beneficial. Fibroblasts, tenocytes, tendon-bone interface cells, bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived stem cells (ADSCs) and tendon stem/progenitor cells (TSPCs) are the cells that, once added at the repair site, gave the best outcomes, and their positive effect could be further increased by transducing the cells with important transcription factors or growth factors. The growth factors that are mostly associated with a benefit are platelet-derived growth factor BB (PDGF-BB), fibroblast growth factor 2 (FGF-2) and growth differentiation factors 5 to 7 (GDFs 5-7). The application of platelet-rich plasma (PRP) at the repair site was found to be beneficial and this effect was further increased by combination with bioactive glass powder or self-assembled peptide (SAP) gel. Conclusions: Several materials such as SIS, ADM, PLA and PGA have beneficial effects on rotator cuff healing in animals. This is also true for cells (fibroblasts, tenocytes, tendon-bone interface cells, BM- MSCs and TSPCs), growth factors (PDGF-BB, FGF-2, GDFs 5-7) and PRP. However, there is a need to perform studies that compare these different techniques between them because it is difficult to recommend one therapy instead of another. Also further studies that investigate the combination of cell and growth factor therapy are required because until now there is little experimental data available