Therapeutic, III.

Traumatic injuries resulting in peripheral nerve lesions lead to important morbidity with devastating social and economic consequences. When the lesioned nerve cannot be sutured directly, a nerve graft is generally required to bridge the gap. Although autologous nerve grafting is still the first choice for reconstruction, it has the severe disadvantage of the sacrifice of a functional nerve. Research in tissue engineering and nerve regeneration may have a dramatic impact on clinical and surgical treatment of such nerve lesions. The authors review the latest concepts in tissue engineering for nerve repair, including scaffold engineering of neural guides, biomaterial modification, cell therapy, growth factors delivery, and electrical stimulation. Recent literature is reviewed in detail, pointing out the most interesting present achievements and perspectives for future clinical translation. Electronic search of the literature was performed using MEDLINE, Embase, and the Cochrane Library to identify research studies on peripheral nerve regeneration through tissue-engineered conduits. The following medical subject headings were used to carry out a systematic search of the literature: "nerve regeneration", "stem cells", "biomaterial", "extracellular matrix", "functional regeneration", "growth factors" and "microchannels". Included literature was published between 1991 and 2014. The reference lists from the retrieved articles were also reviewed for additional articles. In total, 76 articles were included in this study.

Background and Objectives: Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic global burden. Despite the current treatments available, either surgical or conservative, the tendon healing process is often suboptimal and impaired. This is due to the inherent scarce ability of tendon tissue to repair and return itself to the original structure. Recently, Adipose-derived mesenchymal stem cells (ADSC) and stromal vascular fraction (SVF) have gained a central interest in the scientific community, demonstrating their effectiveness in treatments of acute and chronic tendon disorders in animals and humans. Either enzymatic or mechanical procedures to obtain ADSC and SVF have been described and used in current clinical practice. However, no unified protocols and processes have been established. Materials and Methods: This systematic review aims at providing a comprehensive update of the literature on the clinical application of ADSC enzymatically or mechanically processed to obtain SVF, alone and in association with biomaterials in the local treatment of tendinopathy and tendon injury in vivo, in animal models and humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Thirty-two articles met our inclusion criteria, with a total of 18 studies in animals, 10 studies in humans and 4 studies concerning the application of biomaterials in vivo in animals. The review of the literature suggests that ADSC/SVF therapy can represent a promising alternative in tendonregenerative medicine for the enhancement of tendon healing. Conclusions: Nevertheless, further investigations and randomized control trials are needed to improve the knowledge, standardize the procedures and extend the consensus on their use for such applications.