Construction of multifunctional hydrogel with metal-polyphenol capsules for infected full-thickness skin wound healing

Damaged skin cannot prevent harmful bacteria from invading tissues,causing infected wounds or even severe tissue damage.In this study,we developed a controlled-release antibacterial composite hydrogel system that can promote wound angiogenesis and inhibit inflammation by sustained releasing Cu-Epigallocatechin-3-gallate(Cu-EGCG)nano-capsules.The prepared SilMA/HAMA/Cu-EGCG hydrogel showed an obvious inhibitory effect on Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus).It could also promote the proliferation and migration of L929 fibroblasts.In vivo full-thickness infected wound healing experiments confirmed the angiogenesis and inflammation regulating effect.Accelerate collagen deposition and wound healing speed were also observed in the SilMA/HAMA/Cu-EGCG hydrogel treated group.The findings of this study show the great potential of this controlled-release antibacterial composite hydrogel in the application of chronic wound healing.

Maturation of induced pluripotent stem cell-derived cardiomyocytes and its therapeutic effect on myocardial infarction in mouse

Induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)have an irreplaceable role in the treatment of myocardial infarction(MI),which can be injected into the transplanted area with new cardiomyocytes(Cardiomyocytes,CMs),and improve myocardial function.However,the immaturity of the structure and function of iPSC-CMs is the main bottleneck at present.Since collagen participates in the formation of extracellular matrix(ECM),we synthesized nano colloidal gelatin(Gel)with collagen as the main component,and confirmed that the biomaterial has good biocompatibility and is suitable for cellular in vitro growth.Subsequently,we combined the PI3K/AKT/mTOR pathway inhibitor BEZ-235 with Gel and found that the two combined increased the sarcomere length and action potential amplitude(APA)of iPSC-CMs,and improved the Ca^(2+)processing ability,the maturation of mitochondrial morphological structure and metabolic function.Not only that,Gel can also prolong the retention rate of iPSC-CMs in the myocardium and increase the expression of Cx43 and angiogenesis in the transplanted area of mature iPSC-CMs,which also provides a reliable basis for the subsequent treatment of mature iPSC-CMs.

Injectable conductive gelatin methacrylate/oxidized dextran hydrogel encapsulating umbilical cord mesenchymal stem cells for myocardial infarction treatment

Umbilical cord mesenchymal stem cells(UCMSCs)transplantation has been proposed as a promising treatment modality for myocardial infarction(MI),but the low retention rate remains a considerable challenge.Injectable natural polymer hydrogels with conductivity ability are highly desirable as cell delivery vehicles to repair infarct myocardium and restore the cardiac function.In this work,we developed a hydrogel system based on gelatin methacrylate(GelMA)and oxidized dextran(ODEX)as cell delivery vehicles for MI.And dopamine could be used as a reductant of graphene oxide(GO)to form reductive GO(rGO).By adjusting the amount of rGO,the conductivity of hydrogels with 0.5 mg/mL rGO concentration(≈10^(-4)S/cm)was similar to that of natural heart tissue.In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell delivery ability of UCMSCs.More importantly,GelMA-O5/rGO hydrogel could promote UCMSCs growth and proliferation,improve the myocardial differentiation ability of UCMSCs,and up-regulate the expression of cTnI and Cx43.Further in vivo experiments demonstrated that GelMA-O5/rGO/UCMSCs Hydrogel could significantly improve the ejection fraction(EF)of rats and significantly reduce myocardial infarct area compared to PBS group,promote the survival of UCMSCs,enhance the expression level of cTnI and Cx43,and decrease the expression level of caspase-3.The findings of this study suggested that the injectable conductive GelMA-O5/rGO hydrogel encapsulating UCMSCs could improve damaged myocardial tissue and reconstruct myocardial function,which will be a promising therapeutic strategy for cardiac repair.

Advances in 3D bioprinting technology for cardiac tissue engineering and regeneration

Cardiovascular disease is still one of the leading causes of death in the world,and heart transplantation is the current major treatment for end-stage cardiovascular diseases.However,because of the shortage of heart donors,new sources of cardiac regenerative medicine are greatly needed.The prominent development of tissue engineering using bioactive materials has creatively laid a direct promising foundation.Whereas,how to precisely pattern a cardiac structure with complete biological function still requires technological breakthroughs.Recently,the emerging three-dimensional(3D)bioprinting technology for tissue engineering has shown great advantages in generating micro-scale cardiac tissues,which has established its impressive potential as a novel foundation for cardiovascular regeneration.Whether 3D bioprinted hearts can replace traditional heart transplantation as a novel strategy for treating cardiovascular diseases in the future is a frontier issue.In this review article,we emphasize the current knowledge and future perspectives regarding available bioinks,bioprinting strategies and the latest outcome progress in cardiac 3D bioprinting to move this promising medical approach towards potential clinical implementation.

Kidney organoids as a promising tool in nephrology

Kidney disease has become a global public health problem affecting over 750 million people worldwide and imposing a heavy economic burden on patients.The complex architecture of the human kidney makes it very difficult to study the pathophysiology of renal diseases in vitro and to develop effective therapeutic options for patients.Even though cell lines and animal models have enriched our understanding,they fail to recapitulate key aspects of human kidney development and renal disease at cellular and functional levels.Organoids can be derived from either pluripotent stem cells or adult stem cells by strictly regulating key signalling pathways.Today,these self-differentiated organoids represent a promising technology to further understand the human kidney,one of the most complex organs,in an unprecedented way.The newly established protocols improved by organ-on-chip and coculture with immune cells will push kidney organoids towards the next generation.Herein,we focus on recent achievements in the application of kidney organoids in disease modelling,nephrotoxic testing,precision medicine,biobanking,and regenerative therapy,followed by discussions of novel strategies to improve their utility for biomedical research.The applications we discuss may help to provide new ideas in clinical fields.