Exploiting Advanced Hydrogel Technologies to Address Key Challenges in Regenerative Medicine

Abstract

Regenerative medicine aims to tackle a panoply of challenges from repairing focal damage to articular cartilage to preventing pathological tissue remodeling after myocardial infarction. Hydrogels are water‐swollen networks formed from synthetic or naturally derived polymers and are emerging as important tools to address these challenges. Recent advances in hydrogel chemistries are enabling researchers to create hydrogels that can act as 3D ex vivo tissue models, allowing them to explore fundamental questions in cell biology by replicating tissues' dynamic and nonlinear physical properties. Enabled by cutting edge techniques such as 3D bioprinting, cell‐laden hydrogels are also being developed with highly controlled tissue‐specific architectures, vasculature, and biological functions that together can direct tissue repair. Moreover, advanced in situ forming and acellular hydrogels are increasingly finding use as delivery vehicles for bioactive compounds and in mediating host cell response. Here, advances in the design and fabrication of hydrogels for regenerative medicine are reviewed. It is also addressed how controlled chemistries are allowing for precise engineering of spatial and time‐dependent properties in hydrogels with a look to how these materials will eventually translate to clinical applications.

HyStem®: A Unique Clinical Grade Hydrogel for Present and Future Medical Applications

“…The most basic form of the platform is called HyStem-C where the concentration (w/v) ratios of Glycosil:Gelin:Extralink are equal in concentration (w/v) ( Table 2 and Figure 2). Upon mixing, Extralink's acrylates react with the former two components' thiol groups via click chemistry (Michael addition reaction) [13,19]. Crosslinks form in trans (e.g.…”

“…Upon closer inspection, it becomes clear that a non-optimized hydrogel adds additional risk to the success of the therapeutic. HA-only hydrogels (Dermal Fillers, Viscosupplements, Opthalmic and Gynecology hydrogels), must be excluded for anchorage-dependent cells like mesenchymal stem cells (MSC)-they do not provide the requisite cellular attachment sequences required to prevent anoikis [13]. Many hydrogels (Dermal Fillers, Viscosupplements) are also pre-crosslinked within its sterile syringe and are dubbed monolithic [9], preventing homogeneous mixing with drugs or cells.…”

Injectable Cardiac Cell Microdroplets for Tissue Regeneration

“…A promising strategy to protect the injected cells is their encapsulation within 3D hydrogels prior to injection. If the hydrogel contains cell binding motifs, it facilitates cell matrix interaction through cell‐surface receptors and prevents anoikis . Biological motifs in natural hydrogels also affect cell behavior, including growth, migration, maturation, and differentiation.…”

“…If the hydrogel contains cell binding motifs, it facilitates cell matrix interaction through cell-surface receptors and prevents anoikis. [2,3] Biological motifs in natural hydrogels also affect cell behavior, including growth, migration, maturation, and differentiation. Recently, our group has developed a personalized hydrogel, based on the omentum extracellularmatrix (ECM).…”

Dextran‐based hydrogel with enhanced mechanical performance via covalent and non‐covalent cross‐linking units carrying adipose‐derived stem cells toward vascularized bone tissue engineering

“…4,5 Hydrogels, especially glycosaminoglycan-based hydrogels exhibit their utility as structural, bio-instructive and cell-laden implants, showing great promise for biomedical applications. 6,7 The most significance is the 3D network containing massive water, which is similar to highly hydrated extracellular matrix (ECM) of living tissue. However, unlike natural ECM, the highly hydrated nature also results in failure of mechanical performance of hydrogels.…”