Highly superporous cholesterol‐modified poly(2‐hydroxyethyl methacrylate) scaffolds for spinal cord injury repair

Abstract

Modifications of poly(2-hydroxyethyl methacrylate) (PHEMA) with cholesterol and the introduction of large pores have been developed to create highly superporous hydrogels that promote cell-surface interactions and that can serve as a permissive scaffold for spinal cord injury (SCI) treatment. Highly superporous cholesterol-modified PHEMA scaffolds have been prepared by the bulk radical copolymerization of 2-hydroxyethyl methacrylate (HEMA), cholesterol methacrylate (CHLMA), and ethylene dimethacrylate (EDMA) cross-linking agent in the presence of ammonium oxalate crystals to establish interconnected pores in the scaffold. Moreover, 2-[(methoxycarbonyl)methoxy]ethyl methacrylate (MCMEMA) was incorporated in the polymerization recipe and hydrolyzed, thus introducing carboxyl groups in the hydrogel to control its swelling and softness. The hydrogels supported the in vitro adhesion and proliferation of rat mesenchymal stem cells. In an in vivo study of acute rat SCI, hydrogels were implanted to bridge a hemisection cavity. Histological evaluation was done 4 weeks after implantation and revealed the good incorporation of the implanted hydrogels into the surrounding tissue, the progressive infiltration of connective tissue and the ingrowth of neurofilaments, Schwann cells, and blood vessels into the hydrogel pores. The results show that highly superporous cholesterol-modified PHEMA hydrogels have bioadhesive properties and are able to bridge a spinal cord lesion.

Injectable Extracellular Matrix Hydrogels as Scaffolds for Spinal Cord Injury Repair

“…32 In comparison with the synthetic nondegradable materials based on poly(2-hydroxyethyl methacrylate), which we previously developed and evaluated in vivo, 33,34 ECM hydrogels are undoubtedly advantageous, in terms of their injectability, degradability, as well as their biological activity, which is able to modulate the immune response and stimulate vascularization and axonal ingrowth. At the same time, there are also two impediments that hinder the use of ECM hydrogels in their current form as optimal materials for CNS repair: (1) progressive hydrogel contraction in combination with fibroblast-like cells, such as MSCs and (2) rapid in vivo hydrogel degradation, which was too fast to be followed by full tissue reconstruction in the lesion cavity.…”

Regenerative medicine for the treatment of spinal cord injury: more than just promises?

“…Factors affecting cell adhesion to a polymer surface include the chemical composition, the net charge of the surface, and the balance between hydrophilic and hydrophobic micro-domains. To improve the biocompatibility of PHEMA scaffolds, the introduction of groups with positive charges [111] or modification with cholesterol [112,113] has been studied. Modifying the surface of PHEMA-based hydrogels with different surface charges showed that, after implantation into the hemisected spinal cord, hydrogels with positively charged functional groups promoted connective tissue infiltration and extended axonal ingrowth into the hydrogel bridge, compared to negatively or uncharged hydrogels [111].…”

Alginate Hydrogels as Scaffolds and Delivery Systems to Repair the Damaged Spinal Cord

“…Some non‐degradable materials composed of synthetic polymethacrylates have shown notable success as implants due to their stiffness without causing compression of the SC tissue . This feature makes non‐degradable materials favorable to cell encapsulation and to providing the proper 3D networks for bridging neural tissues …”