Modified Hyaluronic Acid-Laminin-Hydrogel as Luminal Filler for Clinically Approved Hollow Nerve Guides in a Rat Critical Defect Size Model

Abstract

Hollow nerve guidance conduits are approved for clinical use for defect lengths of up to 3 cm. This is because also in pre-clinical evaluation they are less effective in the support of nerve regeneration over critical defect lengths. Hydrogel luminal fillers are thought to improve the regeneration outcome by providing an optimized matrix inside bioartificial nerve grafts. We evaluated here a modified hyaluronic acid-laminin-hydrogel (M-HAL) as luminal filler for two clinically approved hollow nerve guides. Collagen-based and chitosan-based nerve guides were filled with M-HAL in two different concentrations and the regeneration outcome comprehensively studied in the acute repair rat sciatic nerve 15 mm critical defect size model. Autologous nerve graft (ANG) repair served as gold-standard control. At 120 days post-surgery, all ANG rats demonstrated electrodiagnostically detectable motor recovery. Both concentrations of the hydrogel luminal filler induced improved regeneration outcome over empty nerve guides. However, neither combination with collagen- nor chitosan-based nerve guides resulted in functional recovery comparable to the ANG repair. In contrast to our previous studies, we demonstrate here that M-HAL slightly improved the overall performance of either empty nerve guide type in the critical defect size model.

Culture Conditions for Human Induced Pluripotent Stem Cell-Derived Schwann Cells: A Two-Centre Study

“…The harvested RNA was then used for reverse transcription applying iScriptTM cDNA Synthesis Kit (BioRad, Hercules, CA, USA) according to the manufacturer’s guidelines. The RT-qPCR was performed as recently described [ 63 , 64 ]. In brief, the reaction mixture was prepared in a MicroAmp reaction plate (Applied Biosystems TM , Foster City, CA, USA) containing 5 µL diluted cDNA, 2 µL forward and reverse primer (1.75 µM each) and 7 µL Power SYBR green PCR Master Mix (Applied Biosystems TM ).…”

Innovations in Peripheral Nerve Regeneration

“…Moreover, the utilization of complexes such as extracellular matrix and exosomes have garnered increasing popularity in research due to their potential to contain multiple factors that favor regeneration. Decellularized extracellular matrix [51][52][53][54] is believed to provide an optimal microenvironment for cell growth and viability, containing a rich network of glycosaminoglycans and neurotrophic growth factors that promote Schwann cell proliferation and facilitate nerve regeneration after decellularization [55]. Hibbitts et al [56] have even explored the specific ratios of ECM components, such as fibronectin and laminin, to optimize axonal regeneration.…”

Hyaluronic Acid‐Based Bioconjugate Systems, Scaffolds, and Their Therapeutic Potential

“…[86] Besides, HA has been also combined with laminin-hydrogel as a luminal filler for collagen-based and chitosan-based nerve conduits that have shown functional recovery and tissue regeneration in the sciatic nerve injury model. [87] The combination of HA with sodium alginate (as bioink system, capable of being printed without employing chemical crosslinking agents) exhibited higher viscosity, by maintaining the gross structure of the total hydrogel, [88] here HA increased the bioactivity of the encapsulated cells. Similarly, the 3D-printed chitosan scaffold, when combined with HA, has shown a higher mechanical strength while maintaining its structure, allowing chondrocytes to infiltrate into the scaffold and colonize the pores, forming fibroblast-like cells and promoting chondrogenesis.…”