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.
Highlights
Their use Regenerative medicine aims to tackle a panoply of challenges from repairing in applications including as soft contact focal damage to articular cartilage to preventing pathological tissue remodeling after myocardial infarction
Most 3D hydrogels allow for modulation of overall ligand density, and there is evidence that poly(ethylene glycol) (PEG) hydrogels modified with dangling RGD-binding sequences do not support cellular interactions below certain concentrations;[25] the role of precise ligand spacing, akin to those that have been examined on 2D surfaces, has only recently been explored in 3D
Exploiting Hydrogel Physical Properties been highly criticized for causing side effects such as inflamma- to Direct Host Cell Response tion when used in off-label procedures,[100] the fundamental idea of using a biomaterial to deliver an active biological molecule is In addition to releasing bioactive factors that can regulate widespread
Summary
It was not long after George Otto Gey managed to culture Henrietta Lacks’s cervical cancer cells in a dish[11] that researchers realized that cells behave differently in the body than they do on tissue culture plastic.[12]. Eileen Gentleman is a Wellcome Trust Research Career Development Fellow in the Centre for Craniofacial and Regenerative Biology at King’s College London. Over the past 15 years, the fields of cell and stem cell biology have uncovered an increasing role for physical properties of the ECM in directing cell behaviors. Materials that control cell morphology, elastic, and viscoelastic properties of cells’ substrates, and micro- and nanoscale topographies, among other factors, have been shown to play important roles in directing stem cell differentiation and driving other fundamental cell behaviors. As our understanding of how physical properties of the ECM direct stem cell fate and tissue formation have grown, we have witnessed a concomitant development of biomaterials that mimic such properties. In 3D, do substrate stiffness and topography play important roles, and cellmediated matrix degradability, cell migration, and physical constraint.[13,14] The field is currently developing new hydrogels that allow us to understand the interplay between these factors, and how they independently and synergistically direct cell behavior
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