Eric S. Nealy, Steven J. Reed, Steven M. Adelmund, Barry A. Badeau, Jared A. Shadish, Emily J. Girard, Kenneth Brasel, Fiona J. Pakiam, Andrew J. Mhyre, Jason P. Price, Surojit Sarkar, Vandana Kalia, Cole A. DeForest, James M. Olson
{"title":"多功能组织注射水凝胶,能够延长生物活性蛋白疗法的水解释放时间","authors":"Eric S. Nealy, Steven J. Reed, Steven M. Adelmund, Barry A. Badeau, Jared A. Shadish, Emily J. Girard, Kenneth Brasel, Fiona J. Pakiam, Andrew J. Mhyre, Jason P. Price, Surojit Sarkar, Vandana Kalia, Cole A. DeForest, James M. Olson","doi":"10.1002/btm2.10668","DOIUrl":null,"url":null,"abstract":"<p>Hydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA-approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)-based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization. Our hydrogel solutions polymerize in situ in a temperature-sensitive manner, persist in tissue, and facilitate the delivery of bioactive therapeutics in subsurface locations. Demonstrating the efficacy of our approach, recombinant anti-CD47 monoclonal antibodies, when incorporated into subsurface-injected hydrogel solutions, exhibited cytotoxic activity against infiltrative high-grade glioma xenografts in the rodent brain. To enhance the gel's versatility, recombinant protein cargos can undergo site-specific modification with hydrolysable “azidoester” adapters, allowing for user-defined release profiles from the hydrogel. Hydrogel-generated gradients of murine CXCL10, linked to intratumorally injected hydrogel solutions via azidoester linkers, resulted in significant recruitment of CD8<sup>+</sup> T-cells and the attenuation of tumor growth in a “cold” syngeneic melanoma model. This study highlights a highly customizable, hydrogel-based delivery system for local protein therapeutic administration to meet diverse clinical needs.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10668","citationCount":"0","resultStr":"{\"title\":\"Versatile tissue-injectable hydrogels capable of the extended hydrolytic release of bioactive protein therapeutics\",\"authors\":\"Eric S. Nealy, Steven J. Reed, Steven M. Adelmund, Barry A. Badeau, Jared A. 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Our hydrogel solutions polymerize in situ in a temperature-sensitive manner, persist in tissue, and facilitate the delivery of bioactive therapeutics in subsurface locations. Demonstrating the efficacy of our approach, recombinant anti-CD47 monoclonal antibodies, when incorporated into subsurface-injected hydrogel solutions, exhibited cytotoxic activity against infiltrative high-grade glioma xenografts in the rodent brain. To enhance the gel's versatility, recombinant protein cargos can undergo site-specific modification with hydrolysable “azidoester” adapters, allowing for user-defined release profiles from the hydrogel. Hydrogel-generated gradients of murine CXCL10, linked to intratumorally injected hydrogel solutions via azidoester linkers, resulted in significant recruitment of CD8<sup>+</sup> T-cells and the attenuation of tumor growth in a “cold” syngeneic melanoma model. 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Versatile tissue-injectable hydrogels capable of the extended hydrolytic release of bioactive protein therapeutics
Hydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA-approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)-based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization. Our hydrogel solutions polymerize in situ in a temperature-sensitive manner, persist in tissue, and facilitate the delivery of bioactive therapeutics in subsurface locations. Demonstrating the efficacy of our approach, recombinant anti-CD47 monoclonal antibodies, when incorporated into subsurface-injected hydrogel solutions, exhibited cytotoxic activity against infiltrative high-grade glioma xenografts in the rodent brain. To enhance the gel's versatility, recombinant protein cargos can undergo site-specific modification with hydrolysable “azidoester” adapters, allowing for user-defined release profiles from the hydrogel. Hydrogel-generated gradients of murine CXCL10, linked to intratumorally injected hydrogel solutions via azidoester linkers, resulted in significant recruitment of CD8+ T-cells and the attenuation of tumor growth in a “cold” syngeneic melanoma model. This study highlights a highly customizable, hydrogel-based delivery system for local protein therapeutic administration to meet diverse clinical needs.
期刊介绍:
Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.