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Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates.


ABSTRACT: The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. 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.

SUBMITTER: Vegas AJ 

PROVIDER: S-EPMC4904301 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates.

Vegas Arturo J AJ   Veiseh Omid O   Doloff Joshua C JC   Ma Minglin M   Tam Hok Hei HH   Bratlie Kaitlin K   Li Jie J   Bader Andrew R AR   Langan Erin E   Olejnik Karsten K   Fenton Patrick P   Kang Jeon Woong JW   Hollister-Locke Jennifer J   Bochenek Matthew A MA   Chiu Alan A   Siebert Sean S   Tang Katherine K   Jhunjhunwala Siddharth S   Aresta-Dasilva Stephanie S   Dholakia Nimit N   Thakrar Raj R   Vietti Thema T   Chen Michael M   Cohen Josh J   Siniakowicz Karolina K   Qi Meirigeng M   McGarrigle James J   Graham Adam C AC   Lyle Stephen S   Harlan David M DM   Greiner Dale L DL   Oberholzer Jose J   Weir Gordon C GC   Langer Robert R   Anderson Daniel G DG  

Nature biotechnology 20160125 3


The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. 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 triaz  ...[more]

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