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The tissue microenvironment is structurally and dynamically complex. Materials designed to interact with diseased or compromised tissue to induce regeneration, or to act as a scaffold for the production of tissues in the laboratory, thus need to be responsive to the microenvironment. For this, researchers leverage increased knowledge of the importance of the spatiotemporal integration of biomaterials with the tissue environment, as well as latest developments in high-resolution technologies in imaging and in materials synthesis and fabrication. Dynamically responsive materials for use in tissue engineering respond to external stimuli or have inherent properties that trigger the targeted, timed release of integral chemical constituents or of incorporated ligands for the controlled repair or remodelling of surrounding tissue. This collection highlights recent impactful advances, published in Nature-branded journals, in such dynamic biomaterials.
Stem cells alter their morphology and differentiate to particular lineages in response to biophysical cues from the surrounding matrix. When the matrix is degradable, however, cell fate is morphology-independent and is directed by the traction forces that the cells actively apply after they have degraded the matrix.
Advances in photochemistry have profoundly impacted the way in which biology is studied. Now, a photoactivated enzymatic patterning method that offers spatiotemporal control over the presentation of bioactive proteins to direct cells in three-dimensional culture significantly expands the available chemical toolbox.
Tuning the reversible chemistries in hydrogels makes it possible to mimic the dynamic nature of the extracellular matrix. Various chemistries have been incorporated to regulate cell spreading, biochemical presentation and matrix mechanics.
Hydrogels are water-containing polymer networks that have been applied in various biological settings. Burdick and Murphy review recent advances in the development of dynamic hydrogels whose properties and mechanics change in response to biological signals.
Studying the effects of extracellular matrix stiffening has been impeded because mostin vitromodels are static. Here, dynamic hydrogels are developed that stiffen in the presence of cells and are used to investigate the short-term (minutes-to-hours) and long-term (days-to-weeks) cellular responses to dynamic stiffening.
In chemistry, some dynamic bonds can be selectively and reversibly broken and reformed in response to an environmental stimulus. This Review article discusses the incorporation of dynamic bonds, or interactions, in polymeric materials and the structural changes and macroscopic responses observed in the presence of different stimuli.
Light-based therapies are of growing importance in medicine, though penetrating tissue and reaching the targeted area can be difficult. Here, the authors report the use of biodegradable waveguides capable of directing light where desired, and demonstrate the potential for wound healing.
An engineered tumour model based on a rolling scaffold–tumour composite strip that can be rapidly disassembled for snapshot analyses preserves cell-to-cell interactions and enables spatial mapping of cell metabolism and cell phenotype.
A supramolecular elastic polymer that is stable in the acidic environment of the stomach but dissolves in the neutral-pH environment of the intestines is shown to function as a safe gastric-retentive device in pigs.
Electrospinning is a useful method of biomaterial fabrication, but a lack of bioactivity in the final construct can limit their application as mimics for biological matrices. Here, the authors fabricate a degradable electrospun scaffold as an in vitro and in vivomimic of the extracellular matrix.
An approach that exploits two bioorthogonal photochemistries to achieve reversible immobilization of full-length proteins in synthetic hydrogels allows for the reversible differentiation of human mesenchymal stem cells to osteoblasts.
Transdermal light-triggered activation of cell-adhesive peptides on the surface of implanted hydrogels alters cell–material interactions, such as cell adhesion and spatial patterning, and fibrous encapsulation and vascularization of the material.
Patterning physiologically relevant proteins in three-dimensional hydrogels without affecting the activity and stability of the proteins has been difficult. Now, by using enzymatic crosslinking reactions, in situ control over the phototriggered immobilization of virtually any desired protein in a synthetic hydrogel is demonstrated. The approach can be used to manipulate cells, as demonstrated by the three-dimensional control of the invasion of mesenchymal stem cells within poly(ethylene glycol) hydrogels.
Adhesive interactions between stem cells and the extracellular matrix are known to regulate stem cell differentiation, yet the underlying mechanisms are not well understood. It is now shown that fate decisions of stem cells encapsulated in covalently crosslinked hydrogels are regulated, independently of matrix mechanics and cell morphology, by the cellular tension generated from cell-induced degradation of the hydrogels.
Cell-laden synthetic hydrogels — formed via a copper-free click reaction between a poly(ethylene glycol) tetra-cyclooctyne and a peptide-diazide — provide a platform to investigate the cells' response to various stimuli during growth. The hydrogel's biochemical aspects are readily controlled by a thiol-ene photocoupling reaction initiated with visible light, whereas the biomechanical properties of the network are altered via a UV-mediated photodegradation.