biostudies-literatureZhou XFundamental Research Funds for the Central UniversitiesNational Natural Science Foundation of ChinaHuadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of ChinaNational Key Research and Development Program of Chinae2308077https://www.ebi.ac.uk/biostudies/studies/S-EPMC11040334biostudies-literatureUnknown11(16)The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinkiAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Poly(Glutamic Acid-Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non-Human Primates.PMC1104033422175152226-2022-00146521031882022YFB3807300LHDMZ22H300011226‐2022‐00146Yao KZhu ZLu ZWei XJi JJia FYe YZhou XLiu WZhang PNi YLiu ZCao WHan HChen YChen SWang YfalsePoly(Glutamic Acid-Lysine) Hydrogels with Alternating Sequence Resist the Foreign Body Response in Rodents and Non-Human Primates.The foreign body response (FBR) to implanted biomaterials and biomedical devices can severely impede their functionality and even lead to failure. The discovery of effective anti-FBR materials remains a formidable challenge. Inspire by the enrichment of glutamic acid (E) and lysine (K) residues on human protein surfaces, a class of zwitterionic polypeptide (ZIP) hydrogels with alternating E and K sequences to mitigate the FBR is prepared. When subcutaneously implanted, the ZIP hydrogels caused minimal inflammation after 2 weeks and no obvious collagen capsulation after 6 months in mice. Importantly, these hydrogels effectively resisted the FBR in non-human primate models for at least 2 months. In addition, the enzymatic degradability of the gel can be controlled by adjusting the crosslinki2024-01-01T00:00:00Z2024 Apr2025-04-22T20:43:55.757Z2025-04-06T03:18:00.145ZS-EPMC110403343840346210.1002/advs.202308077