Bioadhesive Hyaluronic Acid-Based Hydrogels for Spinal Cord Injury

Spinal cord injury (SCI) is a severely traumatic condition that can have a devastating effect on the life of patients. It is estimated that over 130,000 people are affected by SCI each year, often resulting in significant neurological and functional impairments. Current treatments for SCI typically involve surgical interventions and pharmacological agents, but unfortunately, no effective clinical treatment exists. This highlights the urgent need for research and development of new therapies. We develop new mussel-inspired hyaluronic acid hydrogels by hydrazone bonds between two hyaluronic acid derivatives. The functionalization with catechol groups provided crucial enhancement of hydrogels’ adhesive properties, as demonstrated through experimental assays conducted with porcine skin and rat spinal cord. The obtained hydrogels had no adverse effects on neuronal cells (SH-SY5Y) and up-regulated specific neuronal marker β-III tubulin. As the controlled inflammation process is crucial for healing, we loaded the obtained hydrogels with an anti-inflammatory drug, ibuprofen. The results suggested that the bioadhesive hydrogels can fill and remain in the lesion gaps, guide axonal growth and, simultaneously, act as a vehicle for the delivery of bioactive compounds.

Authors and Affiliations:

Diogo Duarte, Cátia Correia, Rui L. Reis, Iva Pashkuleva, Daniela Peixoto, and Natália M. Alves

3B’s Research Group, I3Bs − Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco/Guimarães, Portugal;

ICVS/3B’s−PT Government Associate Laboratory, 4710-057 Braga/Guimarães, Portugal

Abstract:

Spinal cord injuries (SCI) have devastating physical, psychological, and psychosocial consequences for patients. One challenge of nerve tissue repair is the lack of a natural extracellular matrix (ECM) that guides the regenerating axons. Hyaluronic acid (HA) is a major ECM component and plays a fundamental role in facilitating lesion healing. Herein, we developed HA-based adhesive hydrogels by modification of HA with dopamine, a mussel-inspired compound with excellent adhesive properties in an aqueous environment. The hydrogels were loaded with the anti-inflammatory drug ibuprofen and the response of neuronal cells (SH-SY5Y) was evaluated in terms of viability, morphology, and adhesion. The obtained results suggested that the developed materials can bridge lesion gaps, guide axonal growth, and simultaneously act as a vehicle for the delivery of bioactive compounds.

Journal: Biomacromolecules

Link: https://pubs.acs.org/doi/10.1021/acs.biomac.3c01186