Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure

Abstract

Spinal cord injury (SCI) is a devastating condition that leaves patients with limited motor and sensory function at and below the injury site, with little to no hope of a meaningful recovery. Because of their ability to mimic multiple features of central nervous system (CNS) tissues, injectable hydrogels are being developed that can participate as therapeutic agents in reducing secondary injury and in the regeneration of spinal cord tissue. Injectable biomaterials can provide a supportive substrate for tissue regeneration, deliver therapeutic factors, and regulate local tissue physiology. Recent reports of increasing intraspinal pressure after SCI suggest that this physiological change can contribute to injury expansion, also known as secondary injury. Hydrogels contain high water content similar to native tissue, and many hydrogels absorb water and swell after formation. In the case of injectable hydrogels for the spinal cord, this process often occurs in or around the spinal cord tissue, and thus may affect intraspinal pressure. In the future, predictable swelling properties of hydrogels may be leveraged to control intraspinal pressure after injury. Here, we review the physiology of SCI, with special attention to the current clinical and experimental literature, underscoring the importance of controlling intraspinal pressure after SCI. We then discuss how hydrogel fabrication, injection, and swelling can impact intraspinal pressure in the context of developing injectable biomaterials for SCI treatment.

Regenerative Therapies for Spinal Cord Injury

“…In addition, microgels can be used for the delivery of cells, 146,147 drugs, and/or biomolecules, 70,89,148 and they can be interesting formulations to use in regenerative therapy of the spinal cord. For detailed reviews of hydrogels as minimally invasive therapies for spinal cord repair, the authors refer the readers to Perale et al, 127 Macaya and Spector, 126 Pakulska et al 148 and Khaing et al 149 The use of polyethylene glycol (PEG), an FDA-approved biomaterial used for many applications, is considered promising for the treatment of SCI because it can support stem cell growth, migration, proliferation, and differentiation. PEG hydrogels can also help to reduce local glial scar invasion, and promote and guide axonal regeneration.…”

Photocrosslinkable Gelatin/Tropoelastin Hydrogel Adhesives for Peripheral Nerve Repair

“…37 Conversely, materials that exhibit limited swelling may be favorable for implantation, as materials with high levels of swelling may increase interstitial pressure at the injury site. 38,39 Therefore, the swellability of GelMA/MeTro hydrogels was evaluated in a model physiological fluid. The swelling ratio of pure GelMA hydrogels was nearly five times that of MeTro after 24 h of incubation in DPBS, while the composites exhibited swelling ratios between that of each pure species (Fig.…”

Conductive and injectable hyaluronic acid/gelatin/gold nanorod hydrogels for enhanced surgical translation and bioprinting

“…In addition to the precursor characterization, the mechanical performance and swelling properties of the crosslinked hydrogels implanted into a SCI were important to characterize because swelling may result in increased intraspinal pressures, which in turn may result in negative clinical outcomes 35 . The GNR hydrogels had increased swelling and absorption of water, and we speculate the cause was limited crosslinking from the high GNR concentrations.…”