Corneal transplantation is an effective clinical treatment for corneal diseases,which,however,is limited by donor corneas.It is of great clinical value to develop bioadhesive corneal patches with functions of“Transpa...Corneal transplantation is an effective clinical treatment for corneal diseases,which,however,is limited by donor corneas.It is of great clinical value to develop bioadhesive corneal patches with functions of“Transparency”and“Epithelium&Stroma generation”,as well as“Suturelessness”and“Toughness”.To simultaneously meet the“T.E.S.T.”requirements,a light-curable hydrogel is designed based on methacryloylated gelatin(GelMA),Pluronic F127 diacrylate(F127DA)&Aldehyded Pluronic F127(AF127)co-assembled bi-functional micelles and collagen type I(COL I),combined with clinically applied corneal cross-linking(CXL)technology for repairing damaged cornea.The patch formed after 5 min of ultraviolet irradiation possesses transparent,highly tough,and strongly bio-adhesive performance.Multiple cross-linking makes the patch withstand deformation near 600%and exhibit a burst pressure larger than 400 mmHg,significantly higher than normal intraocular pressure(10-21 mmHg).Besides,the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo,supporting the regrowth of corneal epithelium and stroma.The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks,showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.展开更多
Platelet-rich plasma(PRP)that has various growth factors has been used clinically in cartilage repair.However,the short residence time and release time at the injury site limit its therapeutic effect.The present study...Platelet-rich plasma(PRP)that has various growth factors has been used clinically in cartilage repair.However,the short residence time and release time at the injury site limit its therapeutic effect.The present study fabricated a granular hydrogel that was assembled from gelatin microspheres and tannic acid through their abundant hydrogen bonding.Gelatin microspheres with the gelatin concentration of 10wt%and the diameter distribution of 1-10 lm were used to assemble by tannic acid to form the granular hydrogel,which exhibited elasticity under low shear strain,but flowability under higher shear strain.The viscosity decreased with the increase in shear rate.Meanwhile,the granular hydrogel exhibited self-healing feature during rheology test.Thus,granular hydrogel carrying PRP not only exhibited well-performed injectability but also performed like a‘plasticine’that possessed good plasticity.The granular hydrogel showed tissue adhesion ability and reactive oxygen species scavenging ability.Granular hydrogel carrying PRP transplanted to full-thickness articular cartilage defects could integrate well with native cartilage,resulting in newly formed cartilage articular fully filled in defects and well-integrated with the native cartilage and subchondral bone.The unique features of the present granular hydrogel,including injectability,plasticity,porous structure,tissue adhesion and reactive oxygen species scavenging provided an ideal PRP carrier toward cartilage tissue engineering.展开更多
Transarterial embolization is a widely recognized clinical treatment method for liver tumors.Given that the soft and easily damaged features of embolic particles may limit tumor embolization efficiency,the present stu...Transarterial embolization is a widely recognized clinical treatment method for liver tumors.Given that the soft and easily damaged features of embolic particles may limit tumor embolization efficiency,the present study carries out an attempt of fabricating tough and elastic microspheric gel for promoting embolization efficiency.To promote the toughness of hydrogel,poly(ethylene glycol)-co-poly(ε-caprolactone)-co-poly(ethylene glycol)(PPP)and PPP with two terminal double bonds(PPPDA)are co-assembled into nano-micelles,which are connected with methacrylated chitosan(CSMA)to fabricate microspheric gels via microfluidic technology.Lowering double bond density of micelles promotes the freedom degree of micelles,significantly enhancing hydrogel toughness.To compensate for the strength loss caused by the decrease of double bond density of micelles,phytic acid(PA)are employed to interact with CS to form a physical network,further improving hydrogel strength and toughness.The CS-PPPDA&PPP-PA microspheric gels exhibit higher blocking effect in vitro.A rabbit VX2 liver metastasis tumor model is prepared to verify the embolization efficacy of CS-PPPDA&PPP-PA microspheric gels.Compared with clinical used microspheres,fewer CS-PPPDA&PPP-PA microspheric gels can achieve enough embolization efficiency.After embolization for 14 days,CS-PPPDA&PPP-PA microspheric gels exhibit improved tumor necrosis rate and promoted tumor cells apoptosis with reduced inflammation in surrounding tissues,confirming advanced embolic efficiency of tough microgels.展开更多
基金This work was supported by the Shanghai Rising-Star Program(Grants No.21QA1401500)Clinical Research Plan of SHDC(Grants No.SHDC2020CR1043B).
文摘Corneal transplantation is an effective clinical treatment for corneal diseases,which,however,is limited by donor corneas.It is of great clinical value to develop bioadhesive corneal patches with functions of“Transparency”and“Epithelium&Stroma generation”,as well as“Suturelessness”and“Toughness”.To simultaneously meet the“T.E.S.T.”requirements,a light-curable hydrogel is designed based on methacryloylated gelatin(GelMA),Pluronic F127 diacrylate(F127DA)&Aldehyded Pluronic F127(AF127)co-assembled bi-functional micelles and collagen type I(COL I),combined with clinically applied corneal cross-linking(CXL)technology for repairing damaged cornea.The patch formed after 5 min of ultraviolet irradiation possesses transparent,highly tough,and strongly bio-adhesive performance.Multiple cross-linking makes the patch withstand deformation near 600%and exhibit a burst pressure larger than 400 mmHg,significantly higher than normal intraocular pressure(10-21 mmHg).Besides,the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo,supporting the regrowth of corneal epithelium and stroma.The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks,showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.
基金supported by the National Natural Science Foundation of China(Grant Nos 82272472,52373146,52173131,51973108)Natural Science Foundation of Shanghai(Grant No.22ZR1424700).
文摘Platelet-rich plasma(PRP)that has various growth factors has been used clinically in cartilage repair.However,the short residence time and release time at the injury site limit its therapeutic effect.The present study fabricated a granular hydrogel that was assembled from gelatin microspheres and tannic acid through their abundant hydrogen bonding.Gelatin microspheres with the gelatin concentration of 10wt%and the diameter distribution of 1-10 lm were used to assemble by tannic acid to form the granular hydrogel,which exhibited elasticity under low shear strain,but flowability under higher shear strain.The viscosity decreased with the increase in shear rate.Meanwhile,the granular hydrogel exhibited self-healing feature during rheology test.Thus,granular hydrogel carrying PRP not only exhibited well-performed injectability but also performed like a‘plasticine’that possessed good plasticity.The granular hydrogel showed tissue adhesion ability and reactive oxygen species scavenging ability.Granular hydrogel carrying PRP transplanted to full-thickness articular cartilage defects could integrate well with native cartilage,resulting in newly formed cartilage articular fully filled in defects and well-integrated with the native cartilage and subchondral bone.The unique features of the present granular hydrogel,including injectability,plasticity,porous structure,tissue adhesion and reactive oxygen species scavenging provided an ideal PRP carrier toward cartilage tissue engineering.
基金supported by the National Natural Science Foundation of China(grant numbers 51973108,52173131)Clinical Specialized Discipline of Health System of Putuo District in Shanghai(grant number 2021tszk01)+2 种基金Technology Innovation Health System of Putuo District in Shanghai(grant number ptkwws202002)Clinical Specialized Discipline of TCM of Putuo District in Shanghai(grant number ptzyzk2101)The research projects at Shanghai University of Traditional Chinese Medicine Affiliated PUTUO Hospital(grant number 2020368B).
文摘Transarterial embolization is a widely recognized clinical treatment method for liver tumors.Given that the soft and easily damaged features of embolic particles may limit tumor embolization efficiency,the present study carries out an attempt of fabricating tough and elastic microspheric gel for promoting embolization efficiency.To promote the toughness of hydrogel,poly(ethylene glycol)-co-poly(ε-caprolactone)-co-poly(ethylene glycol)(PPP)and PPP with two terminal double bonds(PPPDA)are co-assembled into nano-micelles,which are connected with methacrylated chitosan(CSMA)to fabricate microspheric gels via microfluidic technology.Lowering double bond density of micelles promotes the freedom degree of micelles,significantly enhancing hydrogel toughness.To compensate for the strength loss caused by the decrease of double bond density of micelles,phytic acid(PA)are employed to interact with CS to form a physical network,further improving hydrogel strength and toughness.The CS-PPPDA&PPP-PA microspheric gels exhibit higher blocking effect in vitro.A rabbit VX2 liver metastasis tumor model is prepared to verify the embolization efficacy of CS-PPPDA&PPP-PA microspheric gels.Compared with clinical used microspheres,fewer CS-PPPDA&PPP-PA microspheric gels can achieve enough embolization efficiency.After embolization for 14 days,CS-PPPDA&PPP-PA microspheric gels exhibit improved tumor necrosis rate and promoted tumor cells apoptosis with reduced inflammation in surrounding tissues,confirming advanced embolic efficiency of tough microgels.
