Modular, tissue-specific, and biodegradable hydrogel cross-linkers for tissue engineering

Abstract

Synthetic hydrogels are investigated extensively in tissue engineering for their tunable physicochemical properties but are bioinert and lack the tissue-specific cues to produce appropriate biological responses. To introduce tissue-specific biochemical cues to these hydrogels, we have developed a modular hydrogel cross-linker, poly(glycolic acid)–poly(ethylene glycol)–poly(glycolic acid)-di(but-2-yne-1,4-dithiol) (PdBT), that can be functionalized with small peptide-based cues and large macromolecular cues simply by mixing PdBT in water with the appropriate biomolecules at room temperature. Cartilage- and bone-specific PdBT macromers were generated by functionalization with a cartilage-associated hydrophobic N-cadherin peptide, a hydrophilic bone morphogenetic protein peptide, and a cartilage-derived glycosaminoglycan, chondroitin sulfate. These biofunctionalized PdBT macromers can spontaneously cross-link polymers such as poly(N-isopropylacrylamide) to produce rapidly cross-linking, highly swollen, cytocompatible, and hydrolytically degradable hydrogels suitable for mesenchymal stem cell encapsulation. These favorable properties, combined with PdBT’s modular design and ease of functionalization, establish strong potential for its usage in tissue engineering applications.

Click functionalized, tissue‐specific hydrogels for osteochondral tissue engineering

“…All polymers were presterilized by UV exposure for 3 hr, while Teflon molds and other materials were sterilized by autoclaving or ethylene oxide exposure. Hydrogel formulations were optimized and characterized in previous studies, and the total crosslinker concentration in each formulation was set to 25 mM based on the minimum PdBT concentration established in those studies (Guo, Kim, Xie, et al, 2019) and also to maintain equal crosslinking density across conditions. Hydrogel formulations were optimized and characterized in previous studies, and the total crosslinker concentration in each formulation was set to 25 mM based on the minimum PdBT concentration established in those studies (Guo, Kim, Xie, et al, 2019) and also to maintain equal crosslinking density across conditions.…”

“…The synthesis and characterization of PdBT and biofunctionalized PdBT crosslinkers were performed as described in prior studies (Guo, Kim, Xie, et al, 2019) and are briefly summarized here. Azide-modified CS was synthesized as described previously by activated ester chemistry (Guo, Kim, Xie, et al, 2019).…”

“…The synthesis and characterization of PdBT and biofunctionalized PdBT crosslinkers were performed as described in prior studies (Guo, Kim, Xie, et al, 2019) and are briefly summarized here. Azide-modified CS was synthesized as described previously by activated ester chemistry (Guo, Kim, Xie, et al, 2019). NC ("GGGHAVDI"), BMHP1 ("GGGPFSSTKT"), and GHK ("GGGGHKSP") with N-terminal azides were synthesized by solid phase peptide synthesis as described in detail elsewhere (Aulisa, Dong, & Hartgerink, 2009;Guo, Kim, Xie, et al, 2019).…”

“…While the hydrolysis rate of PdBT-crosslinked hydrogels can be modulated by both biomolecule selection and PdBT composition(Guo, Kim, Xie, et al, 2019), further investigation is needed to assess the release rate and bioactivity of com-pounds delivered by PdBT network degradation. Optimization of CS molecular weight and concentration are thus needed to improve chondrogenic performance.…”

Properties of conductive polymer hydrogels and their application in sensors

“…Wearable or implantable devices are in direct contact with the human body and are expected not to cause damage to human health . Due to the unique hydrated environment and adjustable physicochemical properties, CPHs as a good candidate of biocompatible material have been widely used in a large number of biological devices such as biosensor, tissue engineering, controlled drug delivery, and cell culture …”