Modification of tubular chitosan-based peripheral nerve implants: applications for simple or more complex approaches

Abstract

Surgical treatment of peripheral nerve injuries is still a major challenge in human clinic. Up to now, none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve function. This restriction is also effective for novel clinically approved artificial nerve guides. In this review, we compare surgical repair techniques primarily for digital nerve injuries reported with relatively high prevalence to be valuable attempts in clinical digital nerve repair and point out their advantages and shortcomings. We furthermore discuss the use of artificial nerve grafts with a focus on chitosan-based nerve guides, for which our own studies contributed to their approval for clinical use. In the second part of this review, very recent future perspectives for the enhancement of tubular (commonly hollow) nerve guides are discussed in terms of their clinical translatability and ability to form three-dimensional constructs that biomimick the natural nerve structure. This includes materials that have already shown their beneficial potential in in vivo studies like fibrous intraluminal guidance structures, hydrogels, growth factors, and approaches of cell transplantation. Additionally, we highlight upcoming future perspectives comprising co-application of stem cell secretome. From our overview, we conclude that already simple attempts are highly effective to increase the regeneration supporting properties of nerve guides in experimental studies. But for bringing nerve repair with bioartificial nerve grafts to the next level, e.g. repair of defects > 3 cm in human patients, more complex intraluminal guidance structures such as innovatively manufactured hydrogels and likely supplementation of stem cells or their secretome for therapeutic purposes may represent promising future perspectives.

Keywords: bioartificial nerve graft; biological nerve graft; cell transplantation; cellular products; luminal structures; peripheral nerve repair.

Figure 1

Strategies for peripheral nerve repair. Model approaches for peripheral nerve repair in the clinics (left/blue box) are commonly based on transplantation of nerve tissue (autograft or decellularized allograft) or vein transplants filled with muscle fibers. So far, optimal three-dimensional structure and cellular support for successful regeneration is only realized in nerve tissue grafts. Different clinically approved bioartificial nerve grafts exist. With regard to bioartificial nerve graft, this review focuses on recent modifications chitosan-based nerve grafts (pink box) and gives an outlook (green balloon) on promising approaches currently under investigation for further modification of tubular nerve grafts.