In vivointegration of poly(ε-caprolactone)/gelatin nanofibrous nerve guide seeded with teeth derived stem cells for peripheral nerve regeneration

Abstract

Artificial nanofiber nerve guides have gained huge interest in bridging nerve gaps and associated peripheral nerve regeneration due to its high surface area, flexibility and porous structure. In this study, electrospun poly (ε-caprolactone)/gelatin (PCL/Gel) nanofibrous mats were fabricated, rolled around a copper wire and fixed by medical grade adhesive to obtain a tubular shaped bio-graft, to bridge 10 mm sciatic nerve gap in in vivo rat models. Stem cells from human exfoliated deciduous tooth (SHED) were transplanted to the site of nerve injury through the nanofibrous nerve guides. In vivo experiments were performed in animal models after creating a sciatic nerve gap, such that the nerve gap was grafted using (i) nanofiber nerve guide (ii) nanofiber nerve guide seeded with SHED (iii) suturing, while an untreated nerve gap remained as the negative control. In vitro cell culture study was carried out for primary investigation of SHED-nanofiber interaction and its viability within the nerve guides after 2 and 16 weeks of implantation time. Walking track analysis, plantar test, electrophysiology and immunohistochemistry were performed to evaluate functional recovery during nerve regeneration. Vascularization was also investigated by hematoxilin/eosine (H&E) staining. Overall results showed that the SHED seeded on nanofibrous nerve guide could survive and promote axonal regeneration in rat sciatic nerves, whereby the biocompatible PCL/Gel nerve guide with cells can support axonal regeneration and could be a promising tissue engineered graft for peripheral nerve regeneration.

Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

“…It has become a favorite scaffolding material in tissue engineering. [15][16][17][18][19][20] For instance, gelatin can form thermos-reversible hydrogels below their upper critical solution temperature of 25°C-35°C. 21 Gelatinmethacrylamide (GelMA), modification of gelatin with unsaturated methacrylate groups, can be copolymerized to form hydrogel via light or chemical initiators under mild conditions with low cytotoxicity.…”

A scaffold‐free Bio 3D nerve conduit for repair of a 10‐mm peripheral nerve defect in the rats

“…The use of autologous nerve grafts, which promise the most predictable outcomes, has inherent problems such as potential neuroma formation, sensory loss, and tingling sensation at the donor site. Therefore, various materials have been evaluated as alternative treatments for nerve grafts, including non‐synthetic or synthetic conduits, allogenic grafts, and other autologous tissue (Beigi, Ghasemi‐Mobarakeh, Prabhakaran, et al, ; Hundepool, Bulstra, Kotsougiani, et al, ; Manoli, Schulz, Stahl, Jaminet, & Schaller, ).…”

Electrospun polymer nanofibers for medical applications

“…Beigi i współpr. przeprowadzili doświadczenia, w których na rusztowaniu z nanowłókien PCL/żelatyna zaszczepili komórki macierzyste [70]. Po 16 tygodniach kontaktu komórek macierzystych z nanowłóknami za obserwowali regenerację neuronów czuciowych i moto rycznych oraz ich unaczynienie [70].…”