Abstract

Glial cell alignment in tissue engineered constructs is essential for achieving functional outcomes in neural recovery. While gelatin methacrylate (GelMA) hydrogel offers superior biocompatibility along with permissive structure and tailorable mechanical properties, phosphate glass fibers (PGFs) can provide physical cues for directionality of neural growth. Aligned PGFs were fabricated by a melt quenching and fiber drawing method and utilized with synthesized GelMA hydrogel. The mechanical properties of GelMA and biocompatibility of the GelMA-PGFs composite were investigated in vitro using rat glial cells. GelMA with 86% methacrylation degree were photo-crosslinked using 0.1%wt photo-initiator (PI). Photocrosslinking under UV exposure for 60 s was used to produce hydrogels (GelMA-60). PGFs were introduced into the GelMA before crosslinking. Storage modulus and loss modulus of GelMA-60 was 24.73 ± 2.52 and 1.08 ± 0.23 kN/m2 , respectively. Increased cell alignment was observed in GelMA-PGFs compared with GelMA hydrogel alone. These findings suggest GelMA-PGFs can provide glial cells with physical cues necessary to achieve cell alignment. This approach could further be used to achieve glial cell alignment in bioengineered constructs designed to bridge damaged nerve tissue.

Highlights

  • Severe trauma in the central nervous system (CNS) can cause significant nerve injury with loss of tissue integrity and function at the injury site

  • GelMA is a semisynthetic hydrogel, which consists of gelatin coupled with methacrylamide (MA) and the methacrylate groups enables the exploitation of the biological signals inherent in the gelatin molecule, while allowing control of mechanical properties.[17,18]

  • Sterilized 1 cm long, 5 mg mass of Phosphate glass fibers (PGFs) (PGFs – GelMA ratio kept at 2% w/v, was placed into 48 well cell culture plates (Corning®, Labwares, UK) manual separation of fiber bundles was performed with the help of fine tipped tweezers and 250 μL cell loaded hydrogel solution was casted around the PGFs and, and all samples were crosslinked under ultraviolet light (UV) light for 60 s and transferred into culture plates and cultured under 5% CO2 at 37C

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Summary

Introduction

Severe trauma in the central nervous system (CNS) can cause significant nerve injury with loss of tissue integrity and function at the injury site. Over the past few decades, various types of biomaterial scaffolds, processed by methods such as electrospun nanofibers,[6] freeze dried/ solvent cast,[7] self-assembly, gas foaming and hydrogels[8,9,10,11] have been investigated for neural tissue regeneration These studies suggest that polymer-based biomaterial scaffolds can be used to repair CNS injury, alter the microenvironment of lesions, and promote the recovery of neural function.[12] Recently, hydrogel-based biomaterials have gained significant attention in CNS as well as peripheral nerve system (PNS) regeneration applications due to low cost, easy processing, controlled mechanical properties, permeability, and by serving as carriers for bioactive molecules and cell delivery to provide a permissive environment for regeneration. GelMA-based hydrogels have been investigated vastly for potential use in tissue engineering, drug delivery, and 3D bioprinting applications.[20,21,22]

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