Mechanically engineered hydrogel scaffolds for axonal growth and angiogenesis after transplantation in spinal cord injury

Abstract

<jats:p content-type="fine-print"><jats:italic>Object.</jats:italic> Spinal cord injury (SCI) is a complex pathological entity, the treatment of which requires a multipronged approach. One way to integrate different therapeutic strategies for SCI is to develop implantable scaffolds that can deliver therapies in a synergistic manner. Many investigators have developed implantable “bridges,” but an important property of such scaffolds—that is, mechanical compatibility with host tissues—has been neglected. In this study, the authors evaluated the results of implanting a mechanically matched hydrogel-based scaffold to treat SCI.</jats:p> <jats:p content-type="fine-print"><jats:italic>Methods.</jats:italic> A nonbiodegradable hydrogel, poly(2-hydroxyethylmethacrylate) (PHEMA), was engineered using thermally initiated free radical solution polymerization. Two groups of 12 adult Sprague—Dawley rats underwent partial cervical hemisection injury followed by implantation of either PHEMA or PHEMA soaked in 1 µg of brain-derived neurotrophic factor (BDNF). Four rats from each group were killed 1, 2, or 4 weeks after induction of the injury. Immunofluorescence staining was performed to determine the presence of scarring, cellular inflammatory responses, gliosis, angiogenesis, and axonal growth in and around the implanted scaffolds.</jats:p> <jats:p content-type="fine-print"><jats:italic>Conclusions.</jats:italic> The implanted PHEMA with 85% water content had a compressive modulus of 3 to 4 kPa, which matched the spinal cord. Implanted PHEMA elicited modest cellular inflammatory responses that disappeared by 4 weeks and minimal scarring was noted around the matrix. Considerable angiogenesis was observed in PHEMA, and PHEMA soaked in BDNF promoted axonal penetration into the gel. The authors conclude that mechanically engineered PHEMA is well accepted by host tissues and might be used as a platform for sustained drug delivery to promote axonal growth and functional recovery after SCI.</jats:p>

Biomaterials for spinal cord repair

“…in chronic SCi, PHPMA was shown to reduce the lesion cavity volume and induce axon regrowth [116] . one disadvantage compared to PHEMA is that PHPMA shows an increase in regeneration-blocking connective tissue after SCi [117] , which suggests it may work more efficiently when coupled with a drug (such as an matrix metalloproteinase) [53,140,141] MRi [140] BBB [140] iHC [116,142] EM [116,142] Visual examination of movement [116] Treadmill walking [142] Histology [129,143] Antioxidant assay [129] HRP uptake [129] Cutaneous trunci muscle function [119,123,124] Electrophysiology [119,123,124] iHC [134] iHC [133,139,145,146] BBB [92,145] inclined plane [145] Mechanical allodynia [145] Gridwalk [146] Beamwalk [146] SCi model used Complete transection [53,140] Partial hemisection [141] Complete transection [116,142] Hemisection [116] Compression injury [119,123,124,143] PEG ...…”

Neural ECM mimetics

“…Blood vessels are required for the provision of nutrients and removal of waste products, processes that are vital for tissue regeneration (Owen and Shoichet, 2010). Angiogenesis and vascularization of the scaffold implant have been reported for numerous neural ECM biomaterials (Bakshi et al, 2004;Bramfeldt et al, 2010;Estrada et al, 2014;Plant et al, 1997;Woerly et al, 1999).…”

Bioengineering Approaches to Controlled Protein Delivery

“…As described previously, release can sometimes be modulated by cross-link modification, but care must be taken because the procedures used to enhance cross-linking may be detrimental to the protein itself. Using this approach, epidermal growth factor (39), human growth hormone (40), ciliary neurotrophic factor (41), brain-derived neurotrophic factor (42), and neurotrophin-3 (43) have been delivered in various models.…”