This study investigates a novel pH-responsive hydrogel composed of polyvinyl alcohol(PVA)and boric acid(BA)designed for the con-trolled release of salvianolic acid B(SAB),addressing the critical challenge of scar form...This study investigates a novel pH-responsive hydrogel composed of polyvinyl alcohol(PVA)and boric acid(BA)designed for the con-trolled release of salvianolic acid B(SAB),addressing the critical challenge of scar formation and skin regeneration.The dual-crosslinked network architecture of the hydrogel exhibits remark-able pH sensitivity,enabling it to achieve a peak SAB release within 48 hours in the acidic microenvironment characteristic of early-stage wound healing.In vitro assessments demonstrated that the PVA-BA-SAB hydrogel significantly inhibits fibroblast acti-vation and mitigates abnormal collagen deposition,effectively preventing excessive scar formation.Transcriptome sequencing reveals the potential role of PVA-BA-SAB hydrogel in balancing TGF-βand Wnt signaling pathways.Furthermore,in vivo studies revealed enhanced tissue regeneration,characterized by improved collagen organization and increased vascularization,as well as the promotion of mature hair follicle development.The hydrogel’s biocompatibility,mechanical robustness and adhesive properties were also thor-oughly evaluated,confirming its suitability for clinical applications.These findings suggest that the PVA-BA-SAB hydrogel fully exerts the excellent characteristics of biomaterials and maximizes the pharmacological effect of SAB.Our innovative drug delivery system not only facilitates enhanced wound healing but also offers a strategic approach to minimize scarring.This research provides valuable insights into innovative therapeutic strategies for effective wound management and tissue repair.展开更多
The management of diabetic wounds remains a critical therapeutic challenge. Platelet-rich plasma (PRP) gel, PRP-derived exosomes (PRP-Exos), and mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated ther...The management of diabetic wounds remains a critical therapeutic challenge. Platelet-rich plasma (PRP) gel, PRP-derived exosomes (PRP-Exos), and mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated therapeutic potential in wound treatment. Unfortunately, their poor mechanical properties, the short half-lives of growth factors (GFs), and the burst release of GFs and exosomes have limited their clinical applications. Furthermore, proteases in diabetic wounds degrade GFs, which hampers wound repair. Silk fibroin is an enzyme-immobilization biomaterial that could protect GFs from proteases. Herein, we developed novel dual-crosslinked hydrogels based on silk protein (SP) (sericin and fibroin), including SP@PRP, SP@MSC-Exos, and SP@PRP-Exos, to promote diabetic wound healing synergistically. SP@PRP was prepared from PRP and SP using calcium gluconate/thrombin as agonist, while SP@PRP-Exos and SP@MSC-Exos were derived from exosomes and SP with genipin as crosslinker. SP provided improved mechanical properties and enabled the sustained release of GFs and exosomes, thereby overcoming the limitations of PRP and exosomes in wound healing. The dual-crosslinked hydrogels displayed shear-induced thinning, self-healing, and eradication of microbial biofilms in a bone-mimicking environment. In vivo, the dual-crosslinked hydrogels contributed to faster diabetic wound healing than PRP and SP by upregulating GFs expression, down-regulating matrix metalloproteinase-9 expression, and by promoting an anti-NETotic effect, angiogenesis, and re-epithelialization. Hence, these dual-crosslinked hydrogels have the potential to be translated into a new generation of diabetic wound dressings.展开更多
Conventional gel polymer electrolytes based on polymers such as poly(ethylene oxide) face inherent limitations in enhancing ionic conductivity and electrochemical stability.Introducing diverse functional groups into t...Conventional gel polymer electrolytes based on polymers such as poly(ethylene oxide) face inherent limitations in enhancing ionic conductivity and electrochemical stability.Introducing diverse functional groups into the polymer framework enables the precise modulation of its physicochemical properties,thereby influencing the performance of lithium metal batteries.Herein,an in situ dual-crosslinked gel polymer electrolyte based on polyester and polyamide is proposed.This design enables synergistic cation-anion regulation,facilitating continuous Li^(+) transport by abundant ester groups while anchoring the anions by N–H groups.The resulting gel polymer electrolyte exhibits a high ionic conductivity of 0.58 mS cm^(-1)and an elevated Li^(+) transference number of 0.6.The assembled Li||LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2) coin cells achieve 400 cycles at 0.5 C and 300 cycles at 1 C.Furthermore,a 4-layer stacked Li||LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2)(active material mass loading of 26.7 mg cm^(-2)) pouch cell in lean electrolyte conditions(1.7 g Ah^(-1)) is assembled and sustains 45 cycles without obvious decay.This study provides a strategy of synergistic cationanion regulation in gel polymer electrolytes,offering insights for stable lithium metal batteries.展开更多
Methacrylated gelatin(GelMA)hydrogels have been well-recognized as a widely-used natural polymer for biofabrications due to the adaptability for multiple crosslinking schemes,desirable biocompatibility and biodegradab...Methacrylated gelatin(GelMA)hydrogels have been well-recognized as a widely-used natural polymer for biofabrications due to the adaptability for multiple crosslinking schemes,desirable biocompatibility and biodegradability,and ease of chemical functionalization.With regard to 3D bioprinting,however,GelMA has shown unsatisfactory printing stability and accuracy due to slow sol-gel transition,suboptimal mechanical strength,and strict temperature control for printing.We herein developed an innovative dual-crosslinkable colloidal inks composed of self-assembled GelMA nanospheres with 80%self-healing efficiency,which outperform the traditional GelMA polymeric inks in terms of enhanced printability and fidelity,broader printing temperature range,adjustable mechanical strength ranging from brain analogue 2.83 kPa to cardiac analogue 52.45 kPa,and improved bio-functionalities evidenced by the elevated hydrophilicity,mass transfer efficiency and prolonged drug release profile.Moreover,the granulation design of GelMA inks unlocked freeform 3D printing modes such as direct multi-ink writing,embedded printing,but also allowed in-situ printing directly at the bleeding wound sites due to the outstanding hemostatic efficacy and network stability of colloidal gels.In general,our nanostructured GelMA colloidal inks present a better replacement for the traditional GelMA polymeric inks in 3D bioprinting,which establishes a foundation for bench-to-bedside translations of 3D printing techniques towards more practical clinical applications.展开更多
基金supported by the National Key Research and Development Program of China(2022YFA1104600,2022YFA1104604)the National Nature Science Foundation of China(82472166,32471432,52073293,82204326,52273160,31971303)the Science Fund for National Defense Distinguished Young Scholars,and the Beijing Natural Science Foundation(L234066).
文摘This study investigates a novel pH-responsive hydrogel composed of polyvinyl alcohol(PVA)and boric acid(BA)designed for the con-trolled release of salvianolic acid B(SAB),addressing the critical challenge of scar formation and skin regeneration.The dual-crosslinked network architecture of the hydrogel exhibits remark-able pH sensitivity,enabling it to achieve a peak SAB release within 48 hours in the acidic microenvironment characteristic of early-stage wound healing.In vitro assessments demonstrated that the PVA-BA-SAB hydrogel significantly inhibits fibroblast acti-vation and mitigates abnormal collagen deposition,effectively preventing excessive scar formation.Transcriptome sequencing reveals the potential role of PVA-BA-SAB hydrogel in balancing TGF-βand Wnt signaling pathways.Furthermore,in vivo studies revealed enhanced tissue regeneration,characterized by improved collagen organization and increased vascularization,as well as the promotion of mature hair follicle development.The hydrogel’s biocompatibility,mechanical robustness and adhesive properties were also thor-oughly evaluated,confirming its suitability for clinical applications.These findings suggest that the PVA-BA-SAB hydrogel fully exerts the excellent characteristics of biomaterials and maximizes the pharmacological effect of SAB.Our innovative drug delivery system not only facilitates enhanced wound healing but also offers a strategic approach to minimize scarring.This research provides valuable insights into innovative therapeutic strategies for effective wound management and tissue repair.
基金supported by the National Natural Science Foundation of China(51973076)the Fundamental Research Funds for Central Universities(2020kfyXJJS035).
文摘The management of diabetic wounds remains a critical therapeutic challenge. Platelet-rich plasma (PRP) gel, PRP-derived exosomes (PRP-Exos), and mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated therapeutic potential in wound treatment. Unfortunately, their poor mechanical properties, the short half-lives of growth factors (GFs), and the burst release of GFs and exosomes have limited their clinical applications. Furthermore, proteases in diabetic wounds degrade GFs, which hampers wound repair. Silk fibroin is an enzyme-immobilization biomaterial that could protect GFs from proteases. Herein, we developed novel dual-crosslinked hydrogels based on silk protein (SP) (sericin and fibroin), including SP@PRP, SP@MSC-Exos, and SP@PRP-Exos, to promote diabetic wound healing synergistically. SP@PRP was prepared from PRP and SP using calcium gluconate/thrombin as agonist, while SP@PRP-Exos and SP@MSC-Exos were derived from exosomes and SP with genipin as crosslinker. SP provided improved mechanical properties and enabled the sustained release of GFs and exosomes, thereby overcoming the limitations of PRP and exosomes in wound healing. The dual-crosslinked hydrogels displayed shear-induced thinning, self-healing, and eradication of microbial biofilms in a bone-mimicking environment. In vivo, the dual-crosslinked hydrogels contributed to faster diabetic wound healing than PRP and SP by upregulating GFs expression, down-regulating matrix metalloproteinase-9 expression, and by promoting an anti-NETotic effect, angiogenesis, and re-epithelialization. Hence, these dual-crosslinked hydrogels have the potential to be translated into a new generation of diabetic wound dressings.
基金supported by the National Natural Science Foundation of China (92372111,22179070,22279126)the Fundamental Research Funds for the Central Universities (RF1028623157)the Anhui Science Fund for Distinguished Young Scholars(2408085J009)。
文摘Conventional gel polymer electrolytes based on polymers such as poly(ethylene oxide) face inherent limitations in enhancing ionic conductivity and electrochemical stability.Introducing diverse functional groups into the polymer framework enables the precise modulation of its physicochemical properties,thereby influencing the performance of lithium metal batteries.Herein,an in situ dual-crosslinked gel polymer electrolyte based on polyester and polyamide is proposed.This design enables synergistic cation-anion regulation,facilitating continuous Li^(+) transport by abundant ester groups while anchoring the anions by N–H groups.The resulting gel polymer electrolyte exhibits a high ionic conductivity of 0.58 mS cm^(-1)and an elevated Li^(+) transference number of 0.6.The assembled Li||LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2) coin cells achieve 400 cycles at 0.5 C and 300 cycles at 1 C.Furthermore,a 4-layer stacked Li||LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2)(active material mass loading of 26.7 mg cm^(-2)) pouch cell in lean electrolyte conditions(1.7 g Ah^(-1)) is assembled and sustains 45 cycles without obvious decay.This study provides a strategy of synergistic cationanion regulation in gel polymer electrolytes,offering insights for stable lithium metal batteries.
基金supported by the National Key Research and Development Program of China(No.2018YFA0703000)National Natural Science Foundation of China(No.52273102,No.52302344).
文摘Methacrylated gelatin(GelMA)hydrogels have been well-recognized as a widely-used natural polymer for biofabrications due to the adaptability for multiple crosslinking schemes,desirable biocompatibility and biodegradability,and ease of chemical functionalization.With regard to 3D bioprinting,however,GelMA has shown unsatisfactory printing stability and accuracy due to slow sol-gel transition,suboptimal mechanical strength,and strict temperature control for printing.We herein developed an innovative dual-crosslinkable colloidal inks composed of self-assembled GelMA nanospheres with 80%self-healing efficiency,which outperform the traditional GelMA polymeric inks in terms of enhanced printability and fidelity,broader printing temperature range,adjustable mechanical strength ranging from brain analogue 2.83 kPa to cardiac analogue 52.45 kPa,and improved bio-functionalities evidenced by the elevated hydrophilicity,mass transfer efficiency and prolonged drug release profile.Moreover,the granulation design of GelMA inks unlocked freeform 3D printing modes such as direct multi-ink writing,embedded printing,but also allowed in-situ printing directly at the bleeding wound sites due to the outstanding hemostatic efficacy and network stability of colloidal gels.In general,our nanostructured GelMA colloidal inks present a better replacement for the traditional GelMA polymeric inks in 3D bioprinting,which establishes a foundation for bench-to-bedside translations of 3D printing techniques towards more practical clinical applications.
