Thermoreversible laminin‐functionalized hydrogel for neural tissue engineering

Abstract

Traumatic injury to the central nervous system (CNS) triggers cell death and deafferentation, which may activate a cascade of cellular and network disturbances. These events often result in the formation of irregularly shaped lesions comprised of necrotic tissue and/or a fluid-filled cavity. Tissue engineering represents a promising treatment strategy for the injured neural tissue. To facilitate minimally invasive delivery of a tissue engineered system, a thermoreversible polymer is an attractive scaffold candidate. We have developed a bioactive scaffold for neural tissue engineering by tethering laminin-1 (LN) to methylcellulose (MC), a thermoresponsive hydrogel. The base MC chain was oxidized via sodium m-periodate to increase MC tethering capacity. Protein immobilization was facilitated by a Schiff base reaction between primary amine groups on LN and the carbonyl groups of the oxidized MC chain. Immunoassays demonstrated tethering of LN at 1.6 +/- 0.5 ng of LN per milligram of MC. Rheological measurements for different MC-LN constructs indicated MC composition- and MC treatment-dependent effects on solution-gelation transition temperature. Cellular assays with primary rat cortical neurons demonstrated enhanced cell adhesion and viability on LN-functionalized MC when compared with base and oxidized MC. This bioadhesive thermoresponsive scaffold may provide a robust delivery vehicle to injured CNS tissue for neural cell transplantation strategies.

Thermoresponsive Polymers for Biomedical Applications

“…A thermoresponsive methylcellulose based hydrogel was prepared by Stabenfeldt et al [93]. Methylcellulose was conjugated to Laminin protein to produce a physically gelling hydrogel capable of producing a suitable environment for neural tissue growth when injected into a defect in the central nervous system [93].…”

“…Methylcellulose was conjugated to Laminin protein to produce a physically gelling hydrogel capable of producing a suitable environment for neural tissue growth when injected into a defect in the central nervous system [93]. They demonstrated that the addition of the protein conjugate greatly improved the cell viability and adhesion [93].…”

Thermoresponsive hydrogels in biomedical applications

“…Another interesting approach towards a thermosensitive hydrogel system based on methylcellulose was recently reported by Stabenfeldt et al [22]. As it had been shown before [23] that methylcellulose showed low protein adsorption and cell adhesion, Stabenfeldt et al functionalized methylcellulose with the protein laminin, aiming towards the creation of a bioactive scaffold for neural tissue engineering.…”

Biomaterials for the central nervous system

“…A study in vivo showed that MC exhibited minimal inflammatory tissue reaction following implantation into a TBI lesion cavity (Tate et al 2001). MC was further conjugated with laminin-1 (LN) to promote neuronal cell adhesion and survival (Stabenfeldt et al 2006).…”