Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessita...Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.展开更多
More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in applicatio...More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions.To solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable methods.We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro.The STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative adhesions.After two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion barrier.Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations.Our technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.展开更多
Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization.Here,we propose a multi-functional composite hydrogel engineered to overcome such conditions through...Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization.Here,we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel.The composite hydrogel(G-TSrP)is created by combining gelatin methacryloyl(GelMA)and nanoparticles(TSrP)composed of tannic acid(TA)and Sr^(2+).These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation.G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype.It has been observed that the liberation of TA and Sr^(2+)from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages,and thereby,coordinate in vivo adapted degradation of the G-TSrP.Most significantly,G-TSrP accelerates angiogenesis despite the TA’s inhibitory properties,which are counteracted by the released Sr^(2+).Moreover,G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth.Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel.Collectively,these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.展开更多
基金funded by the National Insti-tutes of Health(No.R01 AR074234)AHA collaborative award(No.944227)the Gillian Reny Stepping Strong Center for Trauma Inno-vation at Brigham and Women's Hospital.
文摘Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.
基金funding from the National Institutes of Health(1R01EB023052,1R01HL140618,1R01HL137193,1R01GM126831)the financial support from the Canadian Institutes of Health Research(CIHR)through a postdoctoral fellowshipthe startup fund from the Pennsylvania State University。
文摘More than 90%of surgical patients develop postoper-ative adhesions,and the incidence of hospital re-admissions can be as high as 20%.Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions.To solve thisclinical limitation,we developed an injectable and sprayable shear-thinning hydrogel barrier(STHB)composed of silicate nanoplatelets and poly(ethylene oxide).We optimized this technology to recover mechanical integrity after stress,enabling its delivery though inject-able and sprayable methods.We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro.The STHB was then tested in a rodent model of peritoneal injury to determine its e cacy preventing the formation of postoperative adhesions.After two weeks,the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions,and STHB formulations presented superior e cacy compared to a commercially available adhesion barrier.Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations.Our technology demonstrated increased e cacy,ease of use in complex anatomies,and compatibility with di erent delivery methods,providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.RS-2023-00207746,RS-2023-00207983)a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(grant number:HI19C075300).
文摘Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization.Here,we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel.The composite hydrogel(G-TSrP)is created by combining gelatin methacryloyl(GelMA)and nanoparticles(TSrP)composed of tannic acid(TA)and Sr^(2+).These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation.G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype.It has been observed that the liberation of TA and Sr^(2+)from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages,and thereby,coordinate in vivo adapted degradation of the G-TSrP.Most significantly,G-TSrP accelerates angiogenesis despite the TA’s inhibitory properties,which are counteracted by the released Sr^(2+).Moreover,G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth.Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel.Collectively,these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.