Bacteria can be programmed to deliver natural materials with defined biological and mechanical properties for controlling cell growth and differentiation.Here,we present an elastic,resilient and bioactive polysacchari...Bacteria can be programmed to deliver natural materials with defined biological and mechanical properties for controlling cell growth and differentiation.Here,we present an elastic,resilient and bioactive polysaccharide derived from the extracellular matrix of Pantoea sp.BCCS 001.Specifically,it was methacrylated to generate a new photo crosslinkable hydrogel that we coined Pantoan Methacrylate or put simply PAMA.We have used it for the first time as a tissue engineering hydrogel to treat VML injuries in rats.The crosslinked PAMA hydrogel was super elastic with a recovery nearing 100%,while mimicking the mechanical stiffness of native muscle.After inclusion of thiolated gelatin via a Michaelis reaction with acrylate groups on PAMA we could also guide muscle progenitor cells into fused and aligned tubes-something reminiscent of mature muscle cells.These results were complemented by sarcomeric alpha-actinin immunostaining studies.Importantly,the implanted hydrogels exhibited almost 2-fold more muscle formation and 50%less fibrous tissue formation compared to untreated rat groups.In vivo inflammation and toxicity assays likewise gave rise to positive results confirming the biocompatibility of this new biomaterial system.Overall,our results demonstrate that programmable polysaccharides derived from bacteria can be used to further advance the field of tissue engineering.In greater detail,they could in the foreseeable future be used in practical therapies against VML.展开更多
基金the Danish Council for Independent Research(Technology and Production Sciences,8105-00003B)Denmark,the Novo Nordisk Foundation(NNF22OC0079994 in the call"Project Grants in the Natural and Technical Sciences 2022)+2 种基金Denmark,and the VIDI research programme with project number R0004387which is(partly)financed by The Netherlands Organization for Scientific Research(NWO),The Netherlands.This work has also received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no.951747Masoud Hasany and Mehdi Mehrali would like to acknowledge the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 899987.
文摘Bacteria can be programmed to deliver natural materials with defined biological and mechanical properties for controlling cell growth and differentiation.Here,we present an elastic,resilient and bioactive polysaccharide derived from the extracellular matrix of Pantoea sp.BCCS 001.Specifically,it was methacrylated to generate a new photo crosslinkable hydrogel that we coined Pantoan Methacrylate or put simply PAMA.We have used it for the first time as a tissue engineering hydrogel to treat VML injuries in rats.The crosslinked PAMA hydrogel was super elastic with a recovery nearing 100%,while mimicking the mechanical stiffness of native muscle.After inclusion of thiolated gelatin via a Michaelis reaction with acrylate groups on PAMA we could also guide muscle progenitor cells into fused and aligned tubes-something reminiscent of mature muscle cells.These results were complemented by sarcomeric alpha-actinin immunostaining studies.Importantly,the implanted hydrogels exhibited almost 2-fold more muscle formation and 50%less fibrous tissue formation compared to untreated rat groups.In vivo inflammation and toxicity assays likewise gave rise to positive results confirming the biocompatibility of this new biomaterial system.Overall,our results demonstrate that programmable polysaccharides derived from bacteria can be used to further advance the field of tissue engineering.In greater detail,they could in the foreseeable future be used in practical therapies against VML.
