Xenogeneic Decellularized Extracellular Matrix-based Biomaterials For Peripheral Nerve Repair and Regeneration

Abstract

: Peripheral nerve injury could lead to either impairment or a complete loss of function for affected patients, and a variety of nerve repair materials have been developed for surgical approaches to repair it. Although autologous or allologous tissue-derived biomaterials remain preferred treatment for peripheral nerve injury, the lack of donor sources has led biomedical researchers to explore more other biomaterials. As a reliable alternative, xenogeneic decellularized extracellular matrix (dECM)-based biomaterials have been widely employed for surgical nerve repair. The dECM derived from animal donors is an attractive and unlimited source for xenotransplantation. Meanwhile, as an increasingly popular technique, decellularization could retain a variety of bioactive components in native ECM, such as polysaccharides, proteins, and growth factors. The resulting dECM-based biomaterials preserve a tissue's native microenvironment, promote Schwann cells proliferation and differentiation, and provide cues for nerve regeneration. Although the potential of dECM-based biomaterials as a therapeutic agent is rising, there are many limitations of this material restricting its use. Herein, this review discusses the decellularization techniques that have been applied to create dECM-based biomaterials, the main components of nerve ECM, and the recent progress in the utilization of xenogeneic dECM-based biomaterials through applications as a hydrogel, wrap, and guidance conduit in nerve tissue engineering. In the end, the existing bottlenecks of xenogeneic dECM-based biomaterials and developing technologies that could be eliminated to be helpful for utilization in the future have been elaborated.

High-strength and high-toughness ECM films with the potential for peripheral nerve repair

“…Our results showed that PC12 cells and Schwann cells cultured on ECM films significantly proliferated, and neurite outgrowth of PC12 cells was promoted with earlier neurite elongation and more long-neurites cells over 60 µm, which may benefit from the multiple ECM proteins and binding sites for neurotrophic factors [50]. Previous studies have shown that fibronectin existed in ECM promotes maximum Schwann cell diffusion area, while laminin is most effective in promoting Schwann cell proliferation, cell elongation and c-Jun expression [51]. Compared to commercial rat tail type I collagen, ECM contains exclusive and abundant laminin and type V collagen which could regulate SC gene expression.…”

Traumatic peripheral nerve injuries: diagnosis and management

“…Animal-derived acellular extracellular matrix nerve wraps are also under investigation, and can be similarly employed to avoid risk of antigenic rejection, while minimizing scar tissue formation because of the presence of an intact basement membrane complex [35 ▪ –37 ▪ ]. Synthetic conduits are an appealing alternative; however, they cannot successfully facilitate axonal regeneration over long distances, likely because of the lack of microstructural elements found in native nerve [38]. Newer approaches have focused on customizing nerve guide conduits, such as using 3D printing, and creating synthetic scaffolds infused with neurotrophic factors and lined with Schwann cells to create a favorable microenvironment and facilitate axonal migration along these artificial channels, which may increase the likelihood of successful nerve regeneration [39,40,41 ▪ ,42 ▪▪ ].…”

The success of biomaterial-based tissue engineering strategies for peripheral nerve regeneration

“…Other natural materials, including native fibrin ( Du et al, 2017 ; Wang et al, 2018 ; Razavi et al, 2021 ), collagen ( Saeki et al, 2018 ; Yao et al, 2018 ; He et al, 2021 ; Wang et al, 2021 ; Zheng et al, 2021 ), keratin ( Apel et al, 2008 ; Lin et al, 2012 ; Pace et al, 2014 ), alginate ( Lin et al, 2017 ; Rahmati et al, 2021 ; Abdelbasset et al, 2022 ), chitin ( Bak et al, 2017 ; Lu C. F. et al, 2021 ; Yang et al, 2022b ), chitosan ( Li et al, 2018 ; Vishnoi et al, 2019 ), and silk fibroin ( Carvalho et al, 2021 ; Kim et al, 2021 ; Zhao et al, 2020), as well as extracellular matrix (ECM) ( Li T. et al, 2021 ; Kong et al, 2021 ; Kong et al, 2022 ), have shown great potential in treating long gap nerve defects. For instance, Wang et al prepared a nerve catheter using chitosan/chitin to achieve excellent angiogenesis in nerve regeneration process for successfully repairing the 10 mm sciatic nerve defect in rats ( Wang et al, 2016 ).…”

“…It was found that the use of artificial nerve grafts alone can only repair peripheral nerve defects in short distance. It is difficult to support the regeneration of large gap defects, which may be due to the lack of local support of cells and neurotrophic factors ( Li T. et al, 2021 ; Chen et al, 2022 ). Nerve regrowth largely depends on the biological function exerted by the neurotrophins secreted by the nerve cells for regulating cell viability, migration, and differentiation in the peripheral and central nervous systems.…”