In vivo screening of a large combinatorial library of alginates identifies materials that elicit a substantially reduced foreign body response. The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient1,2,3,4,5,6. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.

Gellan gum is a naturally occurring polymer that can cross-link in the presence of divalent cations to form biocompatible hydrogels. However, physically cross-linked gellan gum hydrogels lose their stability under physiological conditions, thus restricting the applications of these hydrogels in vivo. To improve the mechanical strength of the gels, we incorporated methacrylate into the gellan gum and chemically cross-linked the hydrogel through three polymerization methods: step growth through thiol–ene photoclick chemistry, chain-growth via photopolymerization, and mixed model in which both mechanisms were employed. Methacrylation was confirmed and quantified by proton nuclear magnetic resonance (¹H NMR) and Fourier transform infrared spectroscopy. The mechanical properties and chemistry of the cross-linked gels were systematically altered by varying the reaction conditions. The compression moduli of the resulting hydrogels ranged between 6.4 and 17.2 kPa. The swelling ratios of the hydrogels were correlated with the compression moduli and affected by the addition of calcium. In vitro enzymatic degradation rate was found to depend on the degree of methacrylation. NIH/3T3 fibroblast cell proliferation and morphology were related to substrate stiffness, with a high stiffness leading generally to higher proliferation. The proliferation is further affected by the thiol–ene ratio. These results suggest that a hydrogel platform based on the gellan gum can offer versatile chemical modifications and tunable mechanical properties. The influence of these substrates on cell behavior suggests that the gellan gum hydrogels have the flexibility to be engineered for a variety of biomaterials applications.

This review focuses on soft materials involved in biological and artificial membranes. The illustration is a conceptual scheme of artificial membranes synthesized by human-made hydrophilic and hydrophobic soft materials.