Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving selfhealing in permanently cross-linked hydrogels has remained elusive because of the presence of water and irreversible cross-links. Here, we demonstrate that permanently cross-linked hydrogels can be engineered to exhibit self-healing in an aqueous environment. We achieve this feature by arming the hydrogel network with flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties that allows the side chains to mediate hydrogen bonds across the hydrogel interfaces with minimal steric hindrance and hydrophobic collapse. The self-healing reported here is rapid, occurring within seconds of the insertion of a crack into the hydrogel or juxtaposition of two separate hydrogel pieces. The healing is reversible and can be switched on and off via changes in pH, allowing external control over the healing process. Moreover, the hydrogels can sustain multiple cycles of healing and separation without compromising their mechanical properties and healing kinetics. Beyond revealing how secondary interactions could be harnessed to introduce new functions to chemically crosslinked polymeric systems, we also demonstrate various potential applications of such easy-to-synthesize, smart, self-healing hydrogels.biomimetic materials | hydrophobicity | smart materials | molecular dynamics | adhesives R ecent years have witnessed an increasing interest in the development of "smart" materials that can sense changes in their environment and can accordingly adapt their properties and function, similar to living systems. Over the last decade, we have discovered and demonstrated a class of smart hydrogels that exhibit unique biomimicking functions: thermoresponsive volume phase transitions similar to sea cucumbers (1), self-organization into core-shell hollow structures similar to coconuts (2), shape memory as exhibited by living organisms (2), and metal ion-mediated cementing similar to marine mussels (3). A common thread connecting these smart hydrogels is their possession of a unique balance of hydrophilic and hydrophobic interactions that endows the hydrogels with the biomimicking properties described above. In this study, we demonstrate how this concept of balancing hydrophilic and hydrophobic forces could be exploited to design chemically cross-linked hydrogels with self-healing abilities.Indeed, materials capable of autonomous healing upon damage have numerous potential applications (4-6). So far, self-healing has been demonstrated in linear polymers (7), supramolecular networks (8, 9), dendrimer-clay systems (10), metal ion-polymer systems (11,12), and multicomponent systems (13-17). Whereas multicomponent thermosetting systems harness the ability of embedded chemical agents to repair cracks, supramolecular networks and noncovalent hydrogels employ secondary interactions such as hydrogen bonding, ionic interact...

Synthetic matrices emulating the physicochemical properties of tissue-specific ECMs are being developed at a rapid pace to regulate stem cell fate. Biomaterials containing calcium phosphate (CaP) moieties have been shown to support osteogenic differentiation of stem and progenitor cells and bone tissue formation. By using a mineralized synthetic matrix mimicking a CaP-rich bone microenvironment, we examine a molecular mechanism through which CaP minerals induce osteogenesis of human mesenchymal stem cells with an emphasis on phosphate metabolism. Our studies show that extracellular phosphate uptake through solute carrier family 20 (phosphate transporter), member 1 (SLC20a1) supports osteogenic differentiation of human mesenchymal stem cells via adenosine, an ATP metabolite, which acts as an autocrine/paracrine signaling molecule through A2b adenosine receptor. Perturbation of SLC20a1 abrogates osteogenic differentiation by decreasing intramitochondrial phosphate and ATP synthesis. Collectively, this study offers the demonstration of a previously unknown mechanism for the beneficial role of CaP biomaterials in bone repair and the role of phosphate ions in bone physiology and regeneration. These findings also begin to shed light on the role of ATP metabolism in bone homeostasis, which may be exploited to treat bone metabolic diseases.bone metabolism | mineralized matrix | biomimetic material | phosphate signaling

Bone-mimetic mineral-polymer composite materials have several applications ranging from artificial bone grafts to scaffolds for bone tissue engineering; templated mineralization is an effective approach to fabricate such composites. In this study, we synthesized bone-like composites using synthetic hydrogels having pendant side chains terminating with carboxyl groups as a template for mineralization. The role of matrix hydrophobicity on mineralization was examined using poly(ethylene glycol) hydrogels modified with varying lengths of anionic pendant side chains (CH(2) horizontal lineCHCONH(CH(2))(n)COOH, where n = 1, 3, 5, and 7). The ability of these hydrogels to undergo templated mineralization was found to be strongly dependent upon the length of the pendant side chain as is evident from the extent of calcification and morphology of the minerals. Moreover, mineralized phases formed on the hydrogels were confirmed to resemble apatite-like structures. In addition to demonstrating the importance of material hydrophobicity as a design parameter for the development of bone-like synthetic materials, our study also provides a potential explanation for the in vitro differences between the apatite-nucleating capacity of aspartate-rich osteopontin and glutamate-rich bone sialoprotein.

While elastic modulus is tunable in tissue engineering scaffolds, it is substantially more challenging to tune the Poisson’s ratio of scaffolds. In certain biological applications, scaffolds with a tunable Poisson’s ratio may be more suitable for emulating the behavior of native tissue mechanics. Here, we design and fabricate a scaffold, which exhibits simultaneous negative and positive Poisson’s ratio behavior. Custom-made digital micro-mirror device stereolithography (DMD-SL) was used to fabricate single- and multiple-layer scaffolds using polyethylene glycol (PEG) based biomaterial. These scaffolds are composed of pore structures having special geometries, and deformation mechanisms, which can be tuned to exhibit both negative Poisson’s ratio (NPR) and positive Poisson’s ratio (PPR) behavior in a side-to-side or top-bottom configuration. Strain measurement results demonstrate that analytical deformation models and simulations accurately predict the Poisson’s ratios of both the NPR and PPR regions. This hybrid Poisson’s ratio property can be imparted to any photocurable material, and potentially be applicable in a variety of biomedical applications.