Conductive and transparent dipeptide hydrogels are desirable building blocks to prepare soft electronic devices and wearable biosensors due to their excellent biocompatibility,multi-functionality,and physiochemical pr...Conductive and transparent dipeptide hydrogels are desirable building blocks to prepare soft electronic devices and wearable biosensors due to their excellent biocompatibility,multi-functionality,and physiochemical properties similar to those of body tissues.However,the preparation of such hydrogels featuring high conductivity and transparency is a huge challenge because of the hydrophobic feature of conductive additives making the doping process difficult.To overcome this issue,hydrophilic conductive polydopamine(PDA)-doped polypyrrole(PPy)nanoparticles are introduced into the dipeptide hydrogel networks to form conductive nanofibrils in situ to achieve a good level of hydrophilic templating of the hydrogel networks.This tech-nique creates a complete conductive network and allows visible light to pass through.The strategy proposed herein not only endows the dipeptide hydrogel with good conductivity and high transparency,but also provides a great potential application of conductive dipeptide hydrogels for body-adhered signal detection,as evidenced by the experimental data.展开更多
Effectively managing bone defects presents significant clinical challenges,where bone marrow mesenchymal stem cells(BMSCs)offer promising potential for bone regeneration.However,delivering BMSCs effectively requires s...Effectively managing bone defects presents significant clinical challenges,where bone marrow mesenchymal stem cells(BMSCs)offer promising potential for bone regeneration.However,delivering BMSCs effectively requires suitable biomaterials.Herein,we introduce,Pep1,a calcium-responsive peptide designed for delivering BMSCs for femur regeneration.Pep1self-assembles to form a pericellular hydrogel in the presence of calcium ions,forming a nanofiber-rich network conductive to BMSCs encapsulation.Important,Pep1 hydrogel supports BMSC activity in 3D cell culture without compromise.In vitro and in vivo studies demonstrate excellent biocompatibility of Pep1 hydrogel.Osteogenic differentiation and q-PCR assays reveal that Pep1 enhances osteogenic differentiation and upregulates bone-related genes expression.Furthermore,In vivo experiments confirm that Pep1 hydrogel encapsulating BMSCs significantly improves femur defect repair.This study underscores Pep1 as a promising biomaterial for calcium-responsive bone tissue regeneration.展开更多
Radioresistance reduces the antitumor efficiency of radiotherapy and further restricts its clinical application,which is mainly caused by the aggravation of immunosuppressive tumor microenvironment(ITM).Especially tum...Radioresistance reduces the antitumor efficiency of radiotherapy and further restricts its clinical application,which is mainly caused by the aggravation of immunosuppressive tumor microenvironment(ITM).Especially tumor-associated macrophages(TAMs)usually display the tumor-promoting M2 phenotype during high-dose fractional radiotherapy mediating radiotherapy resistance.Herein,the toll like receptor agonist TLR7/8a was conjugated with radiosensitive peptide hydrogel(Smac-TLR7/8 hydrogel)to regulate TAMs repolarization from M2 type into M1 type,thus modulating the ITM and overcoming the radioresistance.The Smac-TLR7/8 hydrogel was fabricated through self-assembly with nanofibrous morphology,porous structure and excellent biocompatibility.Uponγ-ray radiation,Smac-TLR7/8 hydrogel effectively polarized the macrophages into M1 type.Notably,combined with radiotherapy,TAMs repolarization regulated by Smac-TLR7/8 hydrogel could increase tumor necrosis factor secretion,activate antitumor immune response and effectively inhibit tumor growth.Moreover,TAMs repolarization rebuilt the ITM and elicited the immunogenic phenotypes in solid tumors,thus enhanced the PD1-blockade efficacy through increasing tumor infiltrating lymphocytes(TILs)and decreasing Treg cells in two different immune activity tumor mice models.Overall,this study substantiated that recruiting and repolarization of TAMs were critical in eliciting antitumor immune response and overcoming radioresistance,thus improving the efficacy of radiotherapy and immunotherapy.展开更多
Traumatic brain injury(TBI)impacts over 3.17 million Americans.Management of hemorrhage and coagulation caused by vascular disruption after TBI is critical for the recovery of patients.Cerebrovascular pathologies play...Traumatic brain injury(TBI)impacts over 3.17 million Americans.Management of hemorrhage and coagulation caused by vascular disruption after TBI is critical for the recovery of patients.Cerebrovascular pathologies play an important role in the underlying mechanisms of TBI.The objective of this study is to evaluate a novel regenerative medicine for the injured tissue after brain injury.We utilized a recently described synthetic growth factor with angiogenic potential to facilitate vascular growth in situ at the injury site.Previous work has shown how this injectable self-assembling peptide-based hydrogel(SAPH)creates a regenerative microenvironment for neovascularization at the injury site.Supramolecular assembly allows for thixotropy;the injectable drug delivery system provides sustained in vivo efficacy.In this study,a moderate blunt injury model was used to cause physical vascular damage and hemorrhage.The angiogenic SAPH was then applied directly on the injured rat brain.At day 7 post-TBI,significantly more blood vessels were observed than the sham and injury control group,as well as activation of VEGF-receptor 2,demonstrating the robust angiogenic response elicited by the angiogenic SAPH.Vascular markers von-Willebrand factor(vWF)andα-smooth muscle actin(α-SMA)showed a concomitant increase with blood vessel density in response to the angiogenic SAPH.Moreover,blood brain barrier integrity and blood coagulation were also examined as the parameters to indicate wound recovery post TBI.Neuronal rescue examination by NeuN and myelin basic protein staining showed that the angiogenic SAPH may provide and neuroprotective benefit in the long-term recovery.展开更多
Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for...Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for drug delivery. In this study, we developed a novel and injectable drug delivery platform for the antitumor drug doxorubicin(DOX) using a p H-responsive ionic-complementary octapeptide FOE.This octapeptide could self-assemble into stable hydrogel under neutral conditions, while disassemble under the tumor microenvironment. Especially, at p H 5.8, its micromorphology displayed a transition from nanofibers to nanospheres with the change of secondary structure, which enhanced cellular uptake of DOX. In addition, FOE hydrogel serves as a smart drug reservoir by localized injection to achieve sustained drug release and improve antitumor efficacy. This octapeptide opens up new avenues for promoting the clinical translation of anticancer drugs on account of excellent injectable properties and economic benefits of simple and short sequence.展开更多
Amelogenin can induce odontogenic differentiation of human dental pulp cells(HDPCs),which has great potential and advantages in dentine-pulp complex regeneration.However,the unstability of amelogenin limits its furthe...Amelogenin can induce odontogenic differentiation of human dental pulp cells(HDPCs),which has great potential and advantages in dentine-pulp complex regeneration.However,the unstability of amelogenin limits its further application.This study constructed amelogenin self-assembling peptide hydrogels(L-gel or D-gel)by heating-cooling technique,investigated the effects of these hydrogels on the odontogenic differentiation of HDPCs and explored the underneath mechanism.The critical aggregation concentration,conformation,morphology,mechanical property and biological stability of the hydrogels were characterized,respectively.The effects of the hydrogels on the odontogenic differentiation of HDPCs were evaluated via alkaline phosphatase activity measurement,quantitative reverse transcription polymerase chain reaction,western blot,Alizarin red staining and scanning electron microscope.The mechanism was explored via signaling pathway experiments.Results showed that both the L-gel and D-gel stimulated the odontogenic differentiation of HDPCs on both Day 7 and Day 14,while the D-gel showed the highest enhancement effects.Meanwhile,the D-gel promoted calcium accumulation and mineralized matrix deposition on Day 21.The D-gel activated MAPK-ERK1/2 pathways in HDPCs and induced the odontogenic differentiation via ERK1/2 and transforming growth factor/smad pathways.Overall,our study demonstrated that the amelogenin peptide hydrogel stimulated the odontogenic differentiation and enhanced mineralization,which held big potential in the dentine-pulp complex regeneration.展开更多
Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine.However,there remains a necessity to refine the bio-physi...Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine.However,there remains a necessity to refine the bio-physical and biochemical parameters that govern kidney organoid formation.Differentiation within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and maturation.Here,we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels(SAPHs)of variable stiffness(storage modulus,G′).The resulting organoids con-tained complex structures comparable to those differentiated within the animal-derived matrix,Matrigel.Single-cell RNA sequencing(scRNA-seq)was then used to compare organoids matured within SAPHs to those grown within Matrigel or at the air-liquid interface.A total of 13,179 cells were analysed,revealing 14 distinct clusters.Organoid compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids,while SAPH-derived organoids were enriched for stromal-associated cell populations.Notably,dif-ferentiation within a higher G’SAPH generated podocytes with more mature gene expression profiles.Addi-tionally,maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types,which are a known limitation of current kidney organoid protocols.This work demonstrates the utility of syn-thetic peptide-based hydrogels with a defined stiffness,as a minimally complex microenvironment for the selected differentiation of kidney organoids.展开更多
It remains challenging to develop methods that can precisely control the self-assembling kinetics and thermodynamics of peptide hydrogelators to achieve hydrogels with optimal properties.Here we report the hydrogelati...It remains challenging to develop methods that can precisely control the self-assembling kinetics and thermodynamics of peptide hydrogelators to achieve hydrogels with optimal properties.Here we report the hydrogelation of peptide hydrogelators by an enzymatically induced pH switch,which involves the combination of glucose oxidase and catalase with D-glucose as the substrate,in which both the gelation kinetics and thermodynamics can be controlled by the concentrations of D-glucose.This novel hydrogelation method could result in hydrogels with higher mechanical stability and lower hydrogelation concentrations.We further illustrate the application of this hydrogelation method to differentiate different D-glucose levels.展开更多
The self-assembled peptide-based hydrogels have been widely utilized in foods.However,the self-assembled hydrogels still have some shortages such as low mechanical properties and hydrogel stabilities.Herein,we designe...The self-assembled peptide-based hydrogels have been widely utilized in foods.However,the self-assembled hydrogels still have some shortages such as low mechanical properties and hydrogel stabilities.Herein,we designed two co-assembled C_(13)-WS hydrogels conjugated by Gallic Acid(CA)and Epigallocatechin Gallate(EGCG).The introduction of CA and EGCG into C_(13)-WS hydrogels can significantly improve the mechanical properties and hydrogel stabilities.The storage modulus(G’)values of co-assembled C_(13)-WS/CA and C_(13)-WS/EGCG were 13.33 KPa and 16 KPa,respectively.From transmission electron microscope(TEM)results,CA and EGCG contributed to the rearrangement of C_(13)-WS molecules during co-assembly.Moreover,the self-/co-assembled C_(13)-WS hydrogels showed antimicrobial activity against E.coli,P.aeruginosa,and S.epidermidis.The introduction of CA and EGCG significantly enhanced the antibacterial activity of C_(13)-WS hydrogels.Our findings provide a novel strategy for the development of stable supramolecular antibacterial short peptide hydrogels through co-assembly.展开更多
Following injury in central nervous system（CNS）,there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.T...Following injury in central nervous system（CNS）,there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.The proliferation of a large number of astrocytes results in the formation of glial scar.展开更多
We reported a kind of inorganic-organic hybrid supramolecular hydrogel with excellent anti-biofouling capability. The hydrogel was formed via ionic interaction between the negative-charged sodium polyacrylate （SPA） ...We reported a kind of inorganic-organic hybrid supramolecular hydrogel with excellent anti-biofouling capability. The hydrogel was formed via ionic interaction between the negative-charged sodium polyacrylate （SPA） entwined clay nanosheets （CNS） and positive-charged polyhedral oligomeric silsesquioxane （POSS） core-based generation one （L-Arginine） dendrimer （POSS-R）. Due to their strong ionic interaction, this kind of hydrogel exhibited a rapid gelation behavior which accomplished even at a low POSS-R concentration about 1% w/v. With the increase of POSS-R concentration, these hydrogels appeared more compact structure, accompanied by remarkable enhanced mechanical strength. In addition, these hydrogels demonstrated rapid thixotropic response and shape-memory capability, as well as good hiocompatibility. More importantly, these hydrogels exhibited outstanding anti-biofouling property due to the inherent anti-biofouling capability of SPA. Overall, these findings demonstrated a novel sort of inorganic-organic hybrid supramolecular hydrogel with tunable mechanical strength and excellent anti-biofouling capability, which may have a broad application potential in tissue engineering.展开更多
Redox-enzyme‐mediated electrochemical processes such as hydrogen production,nitrogen fixation,and CO_(2) reduction are at the forefront of the green chemistry revolution.To scale up,the inefficient two‐dimensional(2...Redox-enzyme‐mediated electrochemical processes such as hydrogen production,nitrogen fixation,and CO_(2) reduction are at the forefront of the green chemistry revolution.To scale up,the inefficient two‐dimensional(2D)immobilization of redox enzymes on working electrodes must be replaced by an efficient dense 3D system.Fabrication of 3D electrodes was demonstrated by embedding enzymes in polymer matrices.However,several requirements,such as simple immobilization,prolonged stability,and resistance to enzyme leakage,still need to be addressed.The study presented here aims to overcome these gaps by immobilizing enzymes in a supramolecular hydrogel formed by the self‐assembly of the peptide hydrogelator fluorenylmethyloxycarbonyldiphenylalanine.Harnessing the self‐assembly process avoids the need for tedious and potentially harmful chemistry,allowing the rapid loading of enzymes on a 3D electrode under mild conditions.Using the[FeFe]hydrogenase enzyme,high enzyme loads,prolonged resistance against electrophoresis,and highly efficient hydrogen production are demonstrated.Further,this enzyme retention is shown to arise from its interaction with the peptide nanofibrils.Finally,this method is successfully used to retain other redox enzymes,paving the way for a variety of enzyme‐mediated electrochemical applications.展开更多
Scar formation seriously affects the repair of damaged skin especially in adults and the excessive inflammation has been considered as the reason.The self-assembled peptide-hydrogels are ideal biomaterials for skin wo...Scar formation seriously affects the repair of damaged skin especially in adults and the excessive inflammation has been considered as the reason.The self-assembled peptide-hydrogels are ideal biomaterials for skin wound healing due to their similar nanostructure to natural extracellular matrix,hydration environment and serving as drug delivery systems.In our study,resveratrol,a polyphenol compound with anti-inflammatory effect,is loaded into peptide-hydrogel(Fmoc-FFGGRGD)to form a wound dressing(Pep/RES).Resveratrol is slowly released from the hydrogel in situ,and the release amount is controlled by the loading amount.The in vitro cell experiments demonstrate that the Pep/RES has no cytotoxicity and can inhibit the production of pro-inflammatory cytokines of macrophages.The Pep/RES hydrogels are used as wound dressings in rat skin damage model.The results suggest that the Pep/RES dressing can accelerate wound healing rate,exhibit well-organized collagen deposition,reduce inflammation and eventually prevent scar formation.The Pep/RES hydrogels supply a potential product to develop new skin wound dressings for the therapy of skin damage.展开更多
In vivo,stem cells reside in a three-dimensional(3D)extracellular microenvironment in which complicated biophysical and biochemical factors regulate their behaviors.Biomimicking of the stem cellmatrix interactions is ...In vivo,stem cells reside in a three-dimensional(3D)extracellular microenvironment in which complicated biophysical and biochemical factors regulate their behaviors.Biomimicking of the stem cellmatrix interactions is an ideal approach for controlling the stem cell fate.This study investigates the effects of the incorporation of cell-adhesive ligands in 3D self-assembling peptide hydrogels to modulate stem cell survival,proliferation,maintenance of stemness,and osteogenic differentiation.The results show that the composite hydrogels were non-cytotoxic and effective for maintaining human amniotic mesenchymal stem cell(hAMSC)survival,proliferation and phenotypic characterization.The expression levels of pluripotent markers were also upregulated in the composite hydrogels.Under inductive media conditions,mineral deposition and mRNA expression levels of osteogenic genes of hAMSCs were enhanced.The increasing expression of integrin aand b-subunits for hAMSCs indicates that the ligandintegrin interactions may modulate the cell fate for hAMSCs in composite hydrogels.展开更多
Nerve guidance conduit （NGC） is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment u...Nerve guidance conduit （NGC） is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube （hCST） to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide （RGI, RGIDKRHWNSQ） derived from brain-derived neurotrophic factor （BDNF） to the C-terminus of the self-assembling peptide RADA16-I （Ac-（RADA）4-CONH2）. Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.展开更多
The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics.This study aimed to replicate the characteristics of dental pulp tissue by using c...The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics.This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest(CNC)-like cells(CNCLCs);these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells(iPSCs).CNC is the anterior region of the neural crest in vertebrate embryos,which contains the primordium of dental pulp cells or odontoblasts.The produced CNCLCs showed approximately 2.5-12,000-fold upregulations of major CNC marker genes.Furthermore,the CNCLCs exhibited remarkable odontoblastic differentiation ability,especially when treated with a combination of the fibroblast growth factors(FGFs)FGF4 and FGF9.The FGFs induced odontoblast marker genes by 1.7-5.0-fold,as compared to bone morphogenetic protein 4(BMP4)treatment.In a mouse subcutaneous implant model,the CNCLCs briefly fated with FGF4+FGF9 replicated dental pulp tissue characteristics,such as harboring odontoblast-like cells,a dentin-like layer,and vast neovascularization,induced by the angiogenic self-assembling peptide hydrogel(SAPH),SLan.SLan acts as a versatile biocompatible scaffold in the canal space.This study demonstrated a successful collaboration between regenerative medicine and SAPH technology.展开更多
The in vitro expansion of stem cells is important for their application in different life science fields such as cellular tissue and organ repair.An objective of this paper was to achieve static cell culture in vitro ...The in vitro expansion of stem cells is important for their application in different life science fields such as cellular tissue and organ repair.An objective of this paper was to achieve static cell culture in vitro through peptide hydrogel-supported microspheres(MSs).The peptides,with their gel-forming properties,microstructures,and mechanical strengths characterized,were found to have good support for the MSs and to be injectable.The internal structures of poly(L-lactic acid)microspheres(PLLA-MSs)and polystyrene microspheres(PS-MSs)made in thelaboratory were observed and statistically analyzed in terms of particle size and pore size,following which the co-cultured MSs with cells were found to have good cell adhesion.In addition,three-dimensional(3D)culturing of cells was performed on the peptide and microcarrier composite scaffolds to measure cell viability and cell proliferation.The results showed that the peptides could be stimulated by the culture medium to self-assembly form a 3D fiber network structure.Under the peptide-Ms composite scaffold-based cell culture system,further enhancement of the cell culture effect was measured.The peptide-Ms composite scaffolds have great potential for the application in 3D cell culture and in vitro cellexpansion.展开更多
Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering,but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptid...Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering,but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber.Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification.Herein,a multi-functional supramolecular peptide,P1R16,is developed by coupling a bioactive factor,parathyroid hormone related peptide 1(PTHrP-1),to the basic supramolecular peptide RADA16-I via solid-phase synthesis.It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-I to form nanofiber hydrogels,thus coupling PTHrP-1 to hydrogel matrix.P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner,and P1R16/RADA16-I nanofiber hydrogels promote osteogenesis,angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen(Col)scaffolds.Abundant red blood marrow formation,ideal osteointegration and adapted degradation are observed in the 50%P1R16/Col scaffold group.Therefore,this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.展开更多
基金the Beijing Municipal Natural Science Foundation (No. 7212206)the National Natural Science Foundation of China (Nos. 21774132, 22072155, 22002170, 21571025, and 21601025)Project of Young Science and Technology Star of Dalian (No. 2017RQ156).
文摘Conductive and transparent dipeptide hydrogels are desirable building blocks to prepare soft electronic devices and wearable biosensors due to their excellent biocompatibility,multi-functionality,and physiochemical properties similar to those of body tissues.However,the preparation of such hydrogels featuring high conductivity and transparency is a huge challenge because of the hydrophobic feature of conductive additives making the doping process difficult.To overcome this issue,hydrophilic conductive polydopamine(PDA)-doped polypyrrole(PPy)nanoparticles are introduced into the dipeptide hydrogel networks to form conductive nanofibrils in situ to achieve a good level of hydrophilic templating of the hydrogel networks.This tech-nique creates a complete conductive network and allows visible light to pass through.The strategy proposed herein not only endows the dipeptide hydrogel with good conductivity and high transparency,but also provides a great potential application of conductive dipeptide hydrogels for body-adhered signal detection,as evidenced by the experimental data.
基金supported by the National Natural Science Foundation of China(32401127)the National Youth Talent Support Program(202309460011)+2 种基金the Natural Science Foundation of Hunan(2024JJ5072)the Science and Technology and Development Foundation of Shenzhen(JCYJ20210324122403010 and JCYJ20210324133611030)the Medical and Health Technology Program of Zhejiang Province(2023KY148)。
文摘Effectively managing bone defects presents significant clinical challenges,where bone marrow mesenchymal stem cells(BMSCs)offer promising potential for bone regeneration.However,delivering BMSCs effectively requires suitable biomaterials.Herein,we introduce,Pep1,a calcium-responsive peptide designed for delivering BMSCs for femur regeneration.Pep1self-assembles to form a pericellular hydrogel in the presence of calcium ions,forming a nanofiber-rich network conductive to BMSCs encapsulation.Important,Pep1 hydrogel supports BMSC activity in 3D cell culture without compromise.In vitro and in vivo studies demonstrate excellent biocompatibility of Pep1 hydrogel.Osteogenic differentiation and q-PCR assays reveal that Pep1 enhances osteogenic differentiation and upregulates bone-related genes expression.Furthermore,In vivo experiments confirm that Pep1 hydrogel encapsulating BMSCs significantly improves femur defect repair.This study underscores Pep1 as a promising biomaterial for calcium-responsive bone tissue regeneration.
基金supported by the National Natural Science Foundation of China(No.81971731,82001963,82172082)PUMC Youth Fund and the Fundamental Research Funds for the Central Universities(No.3332020058)+1 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT35031)the Natural Science Fund for Distinguished Young Scholars of Tianjin(18JCJQJC47300)and the CAMS Innovation Fund for Medical Sciences(2021-I2M042).
文摘Radioresistance reduces the antitumor efficiency of radiotherapy and further restricts its clinical application,which is mainly caused by the aggravation of immunosuppressive tumor microenvironment(ITM).Especially tumor-associated macrophages(TAMs)usually display the tumor-promoting M2 phenotype during high-dose fractional radiotherapy mediating radiotherapy resistance.Herein,the toll like receptor agonist TLR7/8a was conjugated with radiosensitive peptide hydrogel(Smac-TLR7/8 hydrogel)to regulate TAMs repolarization from M2 type into M1 type,thus modulating the ITM and overcoming the radioresistance.The Smac-TLR7/8 hydrogel was fabricated through self-assembly with nanofibrous morphology,porous structure and excellent biocompatibility.Uponγ-ray radiation,Smac-TLR7/8 hydrogel effectively polarized the macrophages into M1 type.Notably,combined with radiotherapy,TAMs repolarization regulated by Smac-TLR7/8 hydrogel could increase tumor necrosis factor secretion,activate antitumor immune response and effectively inhibit tumor growth.Moreover,TAMs repolarization rebuilt the ITM and elicited the immunogenic phenotypes in solid tumors,thus enhanced the PD1-blockade efficacy through increasing tumor infiltrating lymphocytes(TILs)and decreasing Treg cells in two different immune activity tumor mice models.Overall,this study substantiated that recruiting and repolarization of TAMs were critical in eliciting antitumor immune response and overcoming radioresistance,thus improving the efficacy of radiotherapy and immunotherapy.
基金This work was supported by grant 1R21AA022734-01A1(to JH)from National Institutes of Health,and NIH R15 EY029504,NSF IIP 1903617,the NJIT Undergraduate Research and Innovation(URI)Program and NJIT Startup funds(to V.A.K.).
文摘Traumatic brain injury(TBI)impacts over 3.17 million Americans.Management of hemorrhage and coagulation caused by vascular disruption after TBI is critical for the recovery of patients.Cerebrovascular pathologies play an important role in the underlying mechanisms of TBI.The objective of this study is to evaluate a novel regenerative medicine for the injured tissue after brain injury.We utilized a recently described synthetic growth factor with angiogenic potential to facilitate vascular growth in situ at the injury site.Previous work has shown how this injectable self-assembling peptide-based hydrogel(SAPH)creates a regenerative microenvironment for neovascularization at the injury site.Supramolecular assembly allows for thixotropy;the injectable drug delivery system provides sustained in vivo efficacy.In this study,a moderate blunt injury model was used to cause physical vascular damage and hemorrhage.The angiogenic SAPH was then applied directly on the injured rat brain.At day 7 post-TBI,significantly more blood vessels were observed than the sham and injury control group,as well as activation of VEGF-receptor 2,demonstrating the robust angiogenic response elicited by the angiogenic SAPH.Vascular markers von-Willebrand factor(vWF)andα-smooth muscle actin(α-SMA)showed a concomitant increase with blood vessel density in response to the angiogenic SAPH.Moreover,blood brain barrier integrity and blood coagulation were also examined as the parameters to indicate wound recovery post TBI.Neuronal rescue examination by NeuN and myelin basic protein staining showed that the angiogenic SAPH may provide and neuroprotective benefit in the long-term recovery.
基金supported by the National Natural Science Foundation of China (Nos. 81572978 and 81760638)Special Science and Frontier Technology Research Project of Chongqing(No. cstc2016jcyj A0520)+1 种基金Innovative Technology in Military and Clinical Medicine (No. 2018JSLC0035)Natural Science Foundation of Xinjiang Province (No. 2017D01C200)。
文摘Since self-assembled peptide hydrogels can solve the problems such as low solubility, poor selectivity and serious adverse effects of traditional chemotherapy drugs, they have been widely used as carrier materials for drug delivery. In this study, we developed a novel and injectable drug delivery platform for the antitumor drug doxorubicin(DOX) using a p H-responsive ionic-complementary octapeptide FOE.This octapeptide could self-assemble into stable hydrogel under neutral conditions, while disassemble under the tumor microenvironment. Especially, at p H 5.8, its micromorphology displayed a transition from nanofibers to nanospheres with the change of secondary structure, which enhanced cellular uptake of DOX. In addition, FOE hydrogel serves as a smart drug reservoir by localized injection to achieve sustained drug release and improve antitumor efficacy. This octapeptide opens up new avenues for promoting the clinical translation of anticancer drugs on account of excellent injectable properties and economic benefits of simple and short sequence.
基金supported by the National Science Fund for Excellent Young Scholars(T2122019)the National Natural Science Foundation of China(51973096,51773097)+4 种基金the Natural Science Foundation of Tianjin City(18JCYBJC27000)the Technology Research and Development Program of Tianjin(20YFZCSY00830)the Tianjin Key Medical Discipline(Specialty)Construction Project(2021-516)the Science and Technology Project of Tianjin Health Commission(ZD20016)the Key Laboratory of Bioactive Materials,Ministry of Education(NKBM-2019-001,NKBM-2019-002).
文摘Amelogenin can induce odontogenic differentiation of human dental pulp cells(HDPCs),which has great potential and advantages in dentine-pulp complex regeneration.However,the unstability of amelogenin limits its further application.This study constructed amelogenin self-assembling peptide hydrogels(L-gel or D-gel)by heating-cooling technique,investigated the effects of these hydrogels on the odontogenic differentiation of HDPCs and explored the underneath mechanism.The critical aggregation concentration,conformation,morphology,mechanical property and biological stability of the hydrogels were characterized,respectively.The effects of the hydrogels on the odontogenic differentiation of HDPCs were evaluated via alkaline phosphatase activity measurement,quantitative reverse transcription polymerase chain reaction,western blot,Alizarin red staining and scanning electron microscope.The mechanism was explored via signaling pathway experiments.Results showed that both the L-gel and D-gel stimulated the odontogenic differentiation of HDPCs on both Day 7 and Day 14,while the D-gel showed the highest enhancement effects.Meanwhile,the D-gel promoted calcium accumulation and mineralized matrix deposition on Day 21.The D-gel activated MAPK-ERK1/2 pathways in HDPCs and induced the odontogenic differentiation via ERK1/2 and transforming growth factor/smad pathways.Overall,our study demonstrated that the amelogenin peptide hydrogel stimulated the odontogenic differentiation and enhanced mineralization,which held big potential in the dentine-pulp complex regeneration.
基金This publication has emanated from research conducted with the financial support of Science Foundation Ireland(SFI)co-funded under the European Regional Development Fund under Grant Number 13/RC/2073_P2+1 种基金The authors acknowledge support from Science Foundation Ireland(16/IA/4584)19/FFP/6833.J.K.W.would also like to acknowledge Royal Society of Chemistry grant(M19-6613).
文摘Human induced pluripotent stem cell(hiPSC)-derived kidney organoids have prospective applications ranging from basic disease modelling to personalised medicine.However,there remains a necessity to refine the bio-physical and biochemical parameters that govern kidney organoid formation.Differentiation within fully-controllable and physiologically relevant 3D growth environments will be critical to improving organoid reproducibility and maturation.Here,we matured hiPSC-derived kidney organoids within fully synthetic self-assembling peptide hydrogels(SAPHs)of variable stiffness(storage modulus,G′).The resulting organoids con-tained complex structures comparable to those differentiated within the animal-derived matrix,Matrigel.Single-cell RNA sequencing(scRNA-seq)was then used to compare organoids matured within SAPHs to those grown within Matrigel or at the air-liquid interface.A total of 13,179 cells were analysed,revealing 14 distinct clusters.Organoid compositional analysis revealed a larger proportion of nephron cell types within Transwell-derived organoids,while SAPH-derived organoids were enriched for stromal-associated cell populations.Notably,dif-ferentiation within a higher G’SAPH generated podocytes with more mature gene expression profiles.Addi-tionally,maturation within a 3D microenvironment significantly reduced the derivation of off-target cell types,which are a known limitation of current kidney organoid protocols.This work demonstrates the utility of syn-thetic peptide-based hydrogels with a defined stiffness,as a minimally complex microenvironment for the selected differentiation of kidney organoids.
基金supported by the National Natural Science Foundation of China(Grant No.11304156)the Priority Academic Program Development of Jiangsu Higher Education,Jiangsu PhD Gathering Scheme,the Technology Foundation for Selected Overseas Chinese Scholar,and the Scientific Research Foundationfor the Returned Overseas Chinese Scholars,State Education Ministry,China
文摘It remains challenging to develop methods that can precisely control the self-assembling kinetics and thermodynamics of peptide hydrogelators to achieve hydrogels with optimal properties.Here we report the hydrogelation of peptide hydrogelators by an enzymatically induced pH switch,which involves the combination of glucose oxidase and catalase with D-glucose as the substrate,in which both the gelation kinetics and thermodynamics can be controlled by the concentrations of D-glucose.This novel hydrogelation method could result in hydrogels with higher mechanical stability and lower hydrogelation concentrations.We further illustrate the application of this hydrogelation method to differentiate different D-glucose levels.
基金supported by China Agriculture Research System of MOF and MARA(CARS-26-07B)Fundamental Research Funds for the Central Universities(2662019PY016,2662020SPPY011)Hubei Province Technology Innovation Special Major Project(2018ABA072).
文摘The self-assembled peptide-based hydrogels have been widely utilized in foods.However,the self-assembled hydrogels still have some shortages such as low mechanical properties and hydrogel stabilities.Herein,we designed two co-assembled C_(13)-WS hydrogels conjugated by Gallic Acid(CA)and Epigallocatechin Gallate(EGCG).The introduction of CA and EGCG into C_(13)-WS hydrogels can significantly improve the mechanical properties and hydrogel stabilities.The storage modulus(G’)values of co-assembled C_(13)-WS/CA and C_(13)-WS/EGCG were 13.33 KPa and 16 KPa,respectively.From transmission electron microscope(TEM)results,CA and EGCG contributed to the rearrangement of C_(13)-WS molecules during co-assembly.Moreover,the self-/co-assembled C_(13)-WS hydrogels showed antimicrobial activity against E.coli,P.aeruginosa,and S.epidermidis.The introduction of CA and EGCG significantly enhanced the antibacterial activity of C_(13)-WS hydrogels.Our findings provide a novel strategy for the development of stable supramolecular antibacterial short peptide hydrogels through co-assembly.
基金supported by National Basic Research Program of China(973 Program,2014CB542205)Hong Kong RGC grant+2 种基金Hong Kong Health and Medical Research Fundfoundation for Distinguished Young Talents in Higher Education of Guangdong(Yq2013023)the Leading Talents of Guangdong Province(87014002)
文摘Following injury in central nervous system（CNS）,there are pathological changes in the injured region,which include neuronal death,axonal damage and demyelination,inflammatory response and activation of glial cells.The proliferation of a large number of astrocytes results in the formation of glial scar.
基金financial support from the National Natural Science Foundation of China(Nos. 51133004, 81361140343,81621003,and 51503131)the Joint Sino-German Center for Research Promotion(No. GZ905)the International Science and Technology Cooperation Program of China(No. 2015DFE52780)
文摘We reported a kind of inorganic-organic hybrid supramolecular hydrogel with excellent anti-biofouling capability. The hydrogel was formed via ionic interaction between the negative-charged sodium polyacrylate （SPA） entwined clay nanosheets （CNS） and positive-charged polyhedral oligomeric silsesquioxane （POSS） core-based generation one （L-Arginine） dendrimer （POSS-R）. Due to their strong ionic interaction, this kind of hydrogel exhibited a rapid gelation behavior which accomplished even at a low POSS-R concentration about 1% w/v. With the increase of POSS-R concentration, these hydrogels appeared more compact structure, accompanied by remarkable enhanced mechanical strength. In addition, these hydrogels demonstrated rapid thixotropic response and shape-memory capability, as well as good hiocompatibility. More importantly, these hydrogels exhibited outstanding anti-biofouling property due to the inherent anti-biofouling capability of SPA. Overall, these findings demonstrated a novel sort of inorganic-organic hybrid supramolecular hydrogel with tunable mechanical strength and excellent anti-biofouling capability, which may have a broad application potential in tissue engineering.
基金Ministry of Energy,Israel,Grant/Award Numbers:219‐11‐120,222‐11‐065Israel Science Foundation,Grant/Award Number:GA 2185/17。
文摘Redox-enzyme‐mediated electrochemical processes such as hydrogen production,nitrogen fixation,and CO_(2) reduction are at the forefront of the green chemistry revolution.To scale up,the inefficient two‐dimensional(2D)immobilization of redox enzymes on working electrodes must be replaced by an efficient dense 3D system.Fabrication of 3D electrodes was demonstrated by embedding enzymes in polymer matrices.However,several requirements,such as simple immobilization,prolonged stability,and resistance to enzyme leakage,still need to be addressed.The study presented here aims to overcome these gaps by immobilizing enzymes in a supramolecular hydrogel formed by the self‐assembly of the peptide hydrogelator fluorenylmethyloxycarbonyldiphenylalanine.Harnessing the self‐assembly process avoids the need for tedious and potentially harmful chemistry,allowing the rapid loading of enzymes on a 3D electrode under mild conditions.Using the[FeFe]hydrogenase enzyme,high enzyme loads,prolonged resistance against electrophoresis,and highly efficient hydrogen production are demonstrated.Further,this enzyme retention is shown to arise from its interaction with the peptide nanofibrils.Finally,this method is successfully used to retain other redox enzymes,paving the way for a variety of enzyme‐mediated electrochemical applications.
基金This work was financially supported by National Natural Science Foundation of China(81770920 and 31700824)Hubei Provincial Natural Science Foundation of China(2017CFB191).
文摘Scar formation seriously affects the repair of damaged skin especially in adults and the excessive inflammation has been considered as the reason.The self-assembled peptide-hydrogels are ideal biomaterials for skin wound healing due to their similar nanostructure to natural extracellular matrix,hydration environment and serving as drug delivery systems.In our study,resveratrol,a polyphenol compound with anti-inflammatory effect,is loaded into peptide-hydrogel(Fmoc-FFGGRGD)to form a wound dressing(Pep/RES).Resveratrol is slowly released from the hydrogel in situ,and the release amount is controlled by the loading amount.The in vitro cell experiments demonstrate that the Pep/RES has no cytotoxicity and can inhibit the production of pro-inflammatory cytokines of macrophages.The Pep/RES hydrogels are used as wound dressings in rat skin damage model.The results suggest that the Pep/RES dressing can accelerate wound healing rate,exhibit well-organized collagen deposition,reduce inflammation and eventually prevent scar formation.The Pep/RES hydrogels supply a potential product to develop new skin wound dressings for the therapy of skin damage.
基金This work was supported by the National Natural Science Foundation of China(31860265)the Natural Science Research project of Education Department of Guizhou Province(Qian Jiao He KY Zi[2015]418)the National Natural Science Foundation of China(31360232).
文摘In vivo,stem cells reside in a three-dimensional(3D)extracellular microenvironment in which complicated biophysical and biochemical factors regulate their behaviors.Biomimicking of the stem cellmatrix interactions is an ideal approach for controlling the stem cell fate.This study investigates the effects of the incorporation of cell-adhesive ligands in 3D self-assembling peptide hydrogels to modulate stem cell survival,proliferation,maintenance of stemness,and osteogenic differentiation.The results show that the composite hydrogels were non-cytotoxic and effective for maintaining human amniotic mesenchymal stem cell(hAMSC)survival,proliferation and phenotypic characterization.The expression levels of pluripotent markers were also upregulated in the composite hydrogels.Under inductive media conditions,mineral deposition and mRNA expression levels of osteogenic genes of hAMSCs were enhanced.The increasing expression of integrin aand b-subunits for hAMSCs indicates that the ligandintegrin interactions may modulate the cell fate for hAMSCs in composite hydrogels.
文摘Nerve guidance conduit （NGC） is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube （hCST） to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide （RGI, RGIDKRHWNSQ） derived from brain-derived neurotrophic factor （BDNF） to the C-terminus of the self-assembling peptide RADA16-I （Ac-（RADA）4-CONH2）. Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.
基金supported by NIH grants,R01DE025885(E.S),R15EY029504(VAK)National Science Foundation NSF IIP 1903617(VAK).
文摘The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics.This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest(CNC)-like cells(CNCLCs);these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells(iPSCs).CNC is the anterior region of the neural crest in vertebrate embryos,which contains the primordium of dental pulp cells or odontoblasts.The produced CNCLCs showed approximately 2.5-12,000-fold upregulations of major CNC marker genes.Furthermore,the CNCLCs exhibited remarkable odontoblastic differentiation ability,especially when treated with a combination of the fibroblast growth factors(FGFs)FGF4 and FGF9.The FGFs induced odontoblast marker genes by 1.7-5.0-fold,as compared to bone morphogenetic protein 4(BMP4)treatment.In a mouse subcutaneous implant model,the CNCLCs briefly fated with FGF4+FGF9 replicated dental pulp tissue characteristics,such as harboring odontoblast-like cells,a dentin-like layer,and vast neovascularization,induced by the angiogenic self-assembling peptide hydrogel(SAPH),SLan.SLan acts as a versatile biocompatible scaffold in the canal space.This study demonstrated a successful collaboration between regenerative medicine and SAPH technology.
基金supported by the National Key Research andDevelopment Program of China(Grant No.2021YFC2101400).
文摘The in vitro expansion of stem cells is important for their application in different life science fields such as cellular tissue and organ repair.An objective of this paper was to achieve static cell culture in vitro through peptide hydrogel-supported microspheres(MSs).The peptides,with their gel-forming properties,microstructures,and mechanical strengths characterized,were found to have good support for the MSs and to be injectable.The internal structures of poly(L-lactic acid)microspheres(PLLA-MSs)and polystyrene microspheres(PS-MSs)made in thelaboratory were observed and statistically analyzed in terms of particle size and pore size,following which the co-cultured MSs with cells were found to have good cell adhesion.In addition,three-dimensional(3D)culturing of cells was performed on the peptide and microcarrier composite scaffolds to measure cell viability and cell proliferation.The results showed that the peptides could be stimulated by the culture medium to self-assembly form a 3D fiber network structure.Under the peptide-Ms composite scaffold-based cell culture system,further enhancement of the cell culture effect was measured.The peptide-Ms composite scaffolds have great potential for the application in 3D cell culture and in vitro cellexpansion.
基金supported by the National Natural Science Foundation of China(No.82372405,No.81871752)the Fundamental Research Funds for the Central Universities(NO.2042023kf0199)+2 种基金the Key Research and Development Program of Hubei Province(No:2022BCA052)the Key Research and Development Program of Wuhan City(No.2023020402010591)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(No.ZNJC202014).
文摘Supramolecular peptide nanofiber hydrogels are emerging biomaterials for tissue engineering,but it is difficult to fabricate multi-functional systems by simply mixing several short-motif-modified supramolecular peptides because relatively abundant motifs generally hinder nanofiber cross-linking or the formation of long nanofiber.Coupling bioactive factors to the assembling backbone is an ideal strategy to design multi-functional supramolecular peptides in spite of challenging synthesis and purification.Herein,a multi-functional supramolecular peptide,P1R16,is developed by coupling a bioactive factor,parathyroid hormone related peptide 1(PTHrP-1),to the basic supramolecular peptide RADA16-I via solid-phase synthesis.It is found that P1R16 self-assembles into long nanofibers and co-assembles with RADA16-I to form nanofiber hydrogels,thus coupling PTHrP-1 to hydrogel matrix.P1R16 nanofiber retains osteoinductive activity in a dose-dependent manner,and P1R16/RADA16-I nanofiber hydrogels promote osteogenesis,angiogenesis and osteoclastogenesis in vitro and induce multi-functionalized osteoregeneration by intramembranous ossification and bone remodeling in vivo when loaded to collagen(Col)scaffolds.Abundant red blood marrow formation,ideal osteointegration and adapted degradation are observed in the 50%P1R16/Col scaffold group.Therefore,this study provides a promising strategy to develop multi-functional supramolecular peptides and a new method to topically administrate parathyroid hormone or parathyroid hormone related peptides for non-healing bone defects.
