Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

Abstract

Background Context: Disc degeneration is the leading cause of low back pain and is often characterized by a loss of disc height, resulting from cleavage of chondroitin sulfate proteoglycans (CSPGs) present in the nucleus pulposus. Intact CSPGs are critical to water retention and maintenance of the nucleus osmotic pressure. Decellularization of healthy nucleus pulposus tissue has the potential to serve as an ideal matrix for tissue engineering of the disc because of the presence of native disc proteins and CSPGs. Injectable in situ gelling matrices are the most viable therapeutic option to prevent damage to the anulus fibrosus and future disc degeneration.

Extracellular Matrix From Decellularized Wharton’s Jelly Improves the Behavior of Cells From Degenerated Intervertebral Disc

“…Our data are in line with the hypothesis that the strengthening of cell properties in terms of viability and expression of specific proteins at precise times represents an important condition in the perspective of guiding the recovery of cellular functionality and triggering regenerative potential. Therefore, the potential of DWJM to revert degenerated IVD cells can be exploited to carry out an ECM-based intradiscal injectable therapeutic (Tukmachev et al, 2016;Wachs et al, 2017;Porzionato et al, 2018;Zhou et al, 2018). In other words, the presence of DWJM could be sufficient to further the functional recovery of the endogenous cells in the degenerated IVD microenvironment.…”

Decellularization and characterization of a whole intervertebral disk xenograft scaffold

“…The primary objective of decellularizing allogenic or xenogenic tissues for the creation of biomaterial scaffolds is to remove all cells, nuclear material and antigenic epitopes while maintaining critical ECM components, their spatial distribution, relative ratios, and tissue microarchitecture. 22,[28][29][30][31][32][33][34][35][36][37][38] This top-down approach to scaffold development aims to minimize the possibility of immune rejection while yielding a biomimetic scaffold that can promote targeted tissue regeneration. Moreover, this approach offers several advantages compared to building scaffolds from the ground-up including; (1) obtaining a "prefabricated," tissuespecific microarchitecture without employing complex additive manufacturing techniques, which (2) yields scaffolds that provide "built-in" instructional cues to local/seeded cells instructing them to attain tissue-specific phenotypes and contribute to tissue regeneration even in the absence of other exogenous soluble growth and differentiation factors.…”

Translation of an injectable triple-interpenetrating-network hydrogel for intervertebral disc regeneration in a goat model

“…Towards this goal, several biomaterials have been evaluated in vitro for NP regeneration, including thermoreversible hyaluronan grafted poly( N -isopropylacrylamide) hydrogels [16,17], hyaluronic acid and collagen II-based hydrogels [18–23], photocrosslinkable carboxymethylcellulose hydrogels [24,25], and in situ gelling native extracellular matrices [26], among others. Our group recently developed and characterized a triple-interpenetrating network hydrogel for NP regeneration comprised of N- carboxyethyl chitosan, oxidized dextran and teleostean (DCT), which gels in situ via Schiff base formation between the –CHO on the oxidized dextran and the –NH 2 on the teleostean and chitosan [27,28].…”