In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone gra...In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphatebuffered saline.They also demonstrated prolonged and stable release profiles of Mg^(2+)and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg^(2+)and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.展开更多
Postoperative recurrence and metastasis are still the main challenges of cancer therapy.Tumor vaccines that induce potent and long-lasting immune activation have great potential for postoperative cancer therapy.Howeve...Postoperative recurrence and metastasis are still the main challenges of cancer therapy.Tumor vaccines that induce potent and long-lasting immune activation have great potential for postoperative cancer therapy.However,the clinical effects of therapeutic tumor vaccines are unsatisfactory due to immune escape caused by the lack of immunogenicity after surgery and the local fibrosis barrier of the tumor which limits effector T cell infiltration.To overcome these challenges,we developed an injectable hydrogelbased tumor vaccine,RATG,which contains whole tumor cell lysates(TCL),Toll-like receptor(TLR)7/8 agonist imiquimod(R837)and an antifibrotic drug ARV-825.TCL and R837 were loaded onto the hydrogel to achieve a powerful reservoir of antigens and adjuvants that induced potent and lasting immune activation.More importantly,ARV-825 could be slowly and sustainably released in the tumor resection cavity to downregulateα-smooth muscle actin(α-SMA)and collagen levels,disintegrate fibrosis barriers and promote T cell infiltration after immune activation to reduce immune escape.In addition,ARV-825 also directly acted on the remaining tumor cells to degrade bromodomain-containing protein 4(BRD4)which is a critical epigenetic reader overexpressed in tumor cells,inhibiting tumor cell migration and invasion.Therefore,our injectable hydrogel created a powerful immune niche in postoperative tumor resection cavity,significantly enhancing the efficacy of tumor vaccines.Our strategy potently activates the immune system and disintegrates the fibrotic barrier of residual tumors with immune microenvironment remodeling in situ,showing anti-recurrence and anti-metastatic effects,and provides a new paradigm for postoperative treatment of tumors.展开更多
Breast cancer(BC)is a common malignant tumor in women,which seriously affects the health of patients.In this paper,a plasma nano-composite injectable hydrogel CCT@CAD was developed to realize multi-therapy synergistic...Breast cancer(BC)is a common malignant tumor in women,which seriously affects the health of patients.In this paper,a plasma nano-composite injectable hydrogel CCT@CAD was developed to realize multi-therapy synergistic anti-cancer.In the acidic tumor microenvironment,CCT@CAD released Au-modified cerium dioxide loaded with cisplatin(CAD),and the surface charge of CAD changed from negative to positive based on the pH-responsive charge inversion characteristic,which significantly improved the internalization efficiency and permeability of tumor cells to CAD.The introduction of Au nanoparticles endowed CAD with localized surface plasmon resonance(LSPR)effects.This effect enhanced electron transfer to activate the Ce active site on the surface of cerium dioxide,thus enhancing the activity of nanozyme,which enabled CAD to rapidly produce O2 and consume glutathione in tumor cells.Meanwhile,Au nanoparticles endowed CAD with excellent photothermal conversion ability,and local hyperthermia could be realized under near infrared laser irradiation.Animal experimental results showed that the tumor inhibition rate was nearly 100%after 14-day treatment of CCT@CAD.The combination of chemotherapy,photothermal therapy and nanozyme therapy proposed in this study provides a new idea for the treatment of BC.展开更多
Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac re...Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac repair efficiency post-MI, culminating in adverse ventricular remodeling and potential heart failure. To address the diverse pathological stages of MI, an injectable composite hydrogel containing versatile nanoparticles was developed. In this study, mesoporous silicon nanoparticles (MSNs) served as carriers for encapsulating microRNA-29b (miR-29b) mimics with antifibrotic activity, subsequently coated with a complex of natural antioxidant tannic acid and zinc ions (TA/Zn). These nanoparticles were then embedded into a biocompatible alginate hydrogel to enhance retention within the infarcted myocardium. Upon injection into the infarcted region of MI mice, the composite hydrogel gradually released the nanoparticles as it degraded. Initially, the TA/Zn complex on the outer layer scavenged reactive oxygen species, thereby inhibiting cell apoptosis. The subsequent dissociation of the TA/Zn complex led to the release of the encapsulated miR-29b mimics that could inhibit the activation of cardiac fibroblasts and collagen production, thereby alleviating fibrosis progression. Overall, this composite hydrogel demonstrated the potential to reduce infarct size and improve cardiac function, suggesting its promise as a synergistic therapeutic approach for repairing infarcted myocardium.展开更多
Myocardial infarction(MI)continues to be a leading cause of morbidity and mortality in cardiovascular diseases worldwide,severely compromising cardiac structure and function.While conventional treatments-including pha...Myocardial infarction(MI)continues to be a leading cause of morbidity and mortality in cardiovascular diseases worldwide,severely compromising cardiac structure and function.While conventional treatments-including pharmacological interventions,coronary artery bypass grafting(CABG),and percutaneous coronary intervention(PCI)-can effectively restore coronary blood flow,their ability to regenerate cardiomyocytes and substantially improve cardiac function remains limited.In this context,injectable hydrogels have emerged as a groundbreaking therapeutic approach,presenting remarkable potential for MI treatment owing to their exceptional biocompatibility,tunable mechanical properties,and versatile functionality.These hydrogels can form stable three-dimensional networks within infarcted myocardium,not only providing mechanical support to mitigate ventricular wall stress but also serving as delivery platforms for bioactive components such as growth factors,therapeutic drugs,and stem cells.Through multiple mechanisms-including attenuation of oxidative stress and calcium overload to protect cardiomyocytes,stimulation of angiogenesis to enhance tissue perfusion,and regulation of inflammatory responses to reduce fibrotic scarring-injectable hydrogels significantly promote myocardial repair and regeneration.Preclinical studies have consistently validated the therapeutic efficacy of various injectable hydrogel formulations in improving cardiac outcomes post-MI,highlighting their transformative potential in cardiovascular medicine.展开更多
Implantable system maximizes drug concentration and continuously releases drugs near the tumor,which is an effective tool to solve the difficult retention of chemotherapy drugs in bladder cancer.In this work,a novel p...Implantable system maximizes drug concentration and continuously releases drugs near the tumor,which is an effective tool to solve the difficult retention of chemotherapy drugs in bladder cancer.In this work,a novel polysaccharide supramolecular injectable hydrogel(CCA hydrogels for short)is rapidly constructed by simply mixing cationic chitosan,anionic sulfobutyl etherβ-cyclodextrin(SBE-β-CD)and a trace amount of silver ions.The injected hydrogel reconstituted and regained its shape in less than 1 h,and it can still maintain the elasticity suitable for the human body.By packaging the drug directly,the gel achieves a high concentration of doxorubicin,an anticancer drug.Using MB49-luc cells as the model of bladder tumor for anti-tumor in vivo,the CCA-DOX gel has obvious inhibitory effect on bladder tumor,and its inhibitory effect is much greater than that of free DOX.Therefore,this self-healing injectable hydrogel has great potential for in situ treatment of bladder cancer.展开更多
To get a sort of new scaffold material for soft tissue reconstruction,we have prepared XLHA-PNIPAAm and XLHA-MC injectable hydrogels through blending crosslinked HA(XLHA) and two temperature-sensitive materials differ...To get a sort of new scaffold material for soft tissue reconstruction,we have prepared XLHA-PNIPAAm and XLHA-MC injectable hydrogels through blending crosslinked HA(XLHA) and two temperature-sensitive materials differed in degradation poly(N-isopropylacrylamide)(PNIPAAm) and methylcellulose(MC),respectively.We tested the injectablility,enzymatic biodegradability,temperature-sensitivity,structure cytotoxicity and hemolysis of the two injectable hydrogels.Our research has successfully obtained the preparation condition of XLHA-PNIPAAm injectable hydrogel,and verified that adding non-degradable material PNIPAAm can postpone the degradation of HA more effectively than degradable material MC.PNIPAAm prepared with 5 kGy dose radiation,MBAAm/NIPAAm(M/M)=0.015,monomer concentration=3% produced XLHA-PNIPAAm with slowest enzymatic biodegradability.DSC results showed that temperature-sensitivity of the XLHA-PNIPAAm was more stable than that of XLHA-MC.Two composite hydrogels were qualified in cytotoxicity and hemolysis tests and the biocompatibility of XLHA-PNIPAAm hydrogel showed better than XLHA-MC hydrogel.展开更多
Myocardial infarction(MI)triggers adverse remodeling mechanisms,thus leading to heart failure.Since the applica-tion of biomaterial-based scaffolds emerged as a viable approach for providing mechanical support and pro...Myocardial infarction(MI)triggers adverse remodeling mechanisms,thus leading to heart failure.Since the applica-tion of biomaterial-based scaffolds emerged as a viable approach for providing mechanical support and promoting cell growth,injectable hydrogels have garnered substantial attention in MI treatment because of their minimally invasive administration through injection and diminished risk of infection.To fully understand the interplay between inject-able hydrogels and infarcted myocardium repair,this review provides an overview of recent advances in injectable hydrogel-mediated MI therapy,including:I)material designs for repairing the infarcted myocardium,considering the pathophysiological mechanism of MI and design principles for biomaterials in MI treatment;II)the development of injectable functional hydrogels for MI treatment,including conductive,self-healing,drug-loaded,and stimulus-responsive hydrogels;and III)research progress in using injectable hydrogels to restore cardiac function in infarcted myocardium by promoting neovascularization,enhancing cardiomyocyte proliferation,decreasing myocardial fibrosis,and inhibiting excessive inflammation.Overall,this review presents the current state of injectable hydrogel research in MI treatment,offering valuable information to facilitate interdisciplinary knowledge transfer and enable the develop-ment of prognostic markers for suitable injectable materials.展开更多
Current clinical treatments cannot effectively delay the progression of osteoarthritis(OA).Consequently,joint replacement surgery is required for late-stage OA when patients cannot tolerate pain and joint dysfunction....Current clinical treatments cannot effectively delay the progression of osteoarthritis(OA).Consequently,joint replacement surgery is required for late-stage OA when patients cannot tolerate pain and joint dysfunction.Therefore,the prevention of OA progression in the early and middle stages is an urgent clinical problem.In a previous study,we demonstrated that NDRG3-mediated hypoxic response might be closely related to the development and progression of OA.In this study,an injectable thermosensitive hydrogel was established by cross-linking Pluronic F-127 and hyaluronic acid(HA)for the sustained release of hypoxia-induced exosomes(HExos)derived from adipose-derived mesenchymal stem cells.We demonstrated that for OA at the early and middle stages,the HExos-loaded HP hydrogel could maintain the chondrocyte phenotype by enhancing chondrocyte autophagy,reducing chondrocyte apoptosis,and promoting chondrocyte activity and proliferation through the NDRG3-mediated hypoxic response.This novel composite hydrogel,which could activate the NDRG3-mediated hypoxic response,may provide new ideas and a theoretical basis for the treatment of early-and mid-stage OA.展开更多
The impaired function of periodontal ligament stem cells(PDLSCs)impedes restoration of periodontal tissues.The cGAS-cGAMP-STING pathway is an innate immune pathway that sensing cytosolic double-stranded DNA(dsDNA),but...The impaired function of periodontal ligament stem cells(PDLSCs)impedes restoration of periodontal tissues.The cGAS-cGAMP-STING pathway is an innate immune pathway that sensing cytosolic double-stranded DNA(dsDNA),but its role in regulating the function of PDLSCs is still unclear.In this study,we found that mito-chondrial DNA(mtDNA)was released into the cytoplasm through the mitochondrial permeability transition pore(mPTP)in PDLSCs upon inflammation,which binds to cGAS and activated the STING pathway by promoting the production of cGAMP,and ultimately impaired the osteogenic differentiation of PDLSCs.Additionally,it is first found that inflammation can down-regulate the level of the ATP-binding cassette membrane subfamily member C1(ABCC1,a cGAMP exocellular transporter)and ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1,a cGAMP hydrolase),which further aggravated the accumulation of intracellular cGAMP,leading to the persistent activation of the cGAS-STING pathway and thus the impaired the differentiation capacity of PDLSCs.Furthermore,we designed a hydrogel system loaded with a mPTP blocker,an ABCC1 agonist and ENPP1 to promote periodontal tissue regeneration by modulating the production,exocytosis,and clearance of cGAMP.In conclusion,our results highlight the profound effects,and specific mechanisms,of the cGAS-STING pathway on the function of stem cells and propose a new strategy to promote periodontal tissue restoration based on the reestablishment of cGAMP homeostasis.展开更多
Hydrogels with multifunctionalities,including sufficient bonding strength,injectability and self-healing capacity,responsive-adhesive ability,fault-tolerant and repeated tissue adhesion,are urgently demanded for invas...Hydrogels with multifunctionalities,including sufficient bonding strength,injectability and self-healing capacity,responsive-adhesive ability,fault-tolerant and repeated tissue adhesion,are urgently demanded for invasive wound closure and wound healing.Motivated by the adhesive mechanism of mussel and brown algae,bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate(SA),gelatin(GT)and protocatechualdehyde,with ferric ions added,for sutureless post-wound-closure.The dynamic hydrogel cross-linked through Schiff base bond,catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA,endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure,injectability and self-healing capacity,and repeated closure of reopened wounds.Moreover,the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned,which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during surgery.Besides,the hydrogels present good biocompatibility,near-infrared-assisted photothermal antibacterial activity,antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic effect.The in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions,indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant.展开更多
The aim of therapeutic neovascularization is to repair ischemic tissues via formation of new blood vessels by delivery of angiogenic growth factors,stem cells or expansion of pre-existing cells.For efficient neovascul...The aim of therapeutic neovascularization is to repair ischemic tissues via formation of new blood vessels by delivery of angiogenic growth factors,stem cells or expansion of pre-existing cells.For efficient neovascularization,controlled release of growth factors is particularly necessary since bolus injection of molecules generally lead to a poor outcome due to inadequate retention within the injured site.In this regard,injectable hydrogels,made of natural,synthetic or hybrid biomaterials,have become a promising solution for efficient delivery of angiogenic factors or stem and progenitor cells for in situ tissue repair,regeneration and neovascularization.This review article will broadly discuss the state-of-the-art in the development of injectable hydrogels from natural and synthetic precursors,and their applications in ischemic tissue repair and wound healing.We will cover a wide range of in vitro and in vivo studies in testing the functionalities of the engineered injectable hydrogels in promoting tissue repair and neovascularization.We will also discuss some of the injectable hydrogels that exhibit self-healing properties by promoting neovascularization without the presence of angiogenic factors.展开更多
Articular cartilage is an important load-bearing tissue distributed on the surface of diarthrodial joints.Due to its avascular,aneural and non-lymphatic features,cartilage has limited self-regenerative properties.To d...Articular cartilage is an important load-bearing tissue distributed on the surface of diarthrodial joints.Due to its avascular,aneural and non-lymphatic features,cartilage has limited self-regenerative properties.To date,the utilization of biomaterials to aid in cartilage regeneration,especially through the use of injectable scaffolds,has attracted considerable attention.Various materials,therapeutics and fabrication approaches have emerged with a focus on manipulating the cartilage microenvironment to induce the formation of cartilaginous structures that have similar properties to the native tissues.In particular,the design and fabrication of injectable hydrogel-based scaffolds have advanced in recent years with the aim of enhancing its therapeutic efficacy and improving its ease of administration.This review summarizes recent progress in these efforts,including the structural improvement of scaffolds,network cross-linking techniques and strategies for controlled release,which present new opportunities for the development of injectable scaffolds for cartilage regeneration.展开更多
Injectable hydrogel is suitable for the repair of lacunar bone deficiency.This study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel system.With controlla...Injectable hydrogel is suitable for the repair of lacunar bone deficiency.This study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel system.With controllable and adjustable physical and chemical properties,the SMS hydrogel could be easily optimized adaptively to different clinical applications.The SMS hydrogel effectively showed great injectability and shapeability,allowing defect filling with no gap.Moreover,the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation,responsive to the concentration of Ca2+and inflammatory-like pH value in the microenvi-ronment of bone deficiency,respectively.In vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling pathway.The SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial cells.Investigations of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2,which could create a specific favorable environment to induce new bone formation and angiogenesis.Meanwhile,SMS hydrogel was proved to be antibacterial,especially for gram-negative bacteria.Furthermore,in vivo study indicated that SMS could be easily applied for maxillary sinus elevation,inducing sufficient new bone formation.Thus,it is convincing that SMS hydrogel could be potent in a simple,minimally invasive and efficient treatment for the repair of lacunar bone deficiency.展开更多
Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation...Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation of exogenous CMs becomes a promising option for MI treatment.However,the low retention and survival of transplanted cells still limit the clinical translation of cell therapy.Herein,an alginate/fibrin-based injectable hydrogel was prepared for the delivery of neonatal CMs and an angiogen-esis agent vascular endothelial growth factor(VEGF)locally to the infarcted area of the heart.This hydro-gel combined the specific advantages of alginate and fibrin with proper mechanical properties and cell affinity,showing good biocompatibility to support the retention and integration of the transplanted CMs to the host myocardium.Moreover,the delivered VEGF was favorable for the blood recovery to mitigate the ischemic microenvironment of the infarcted area and thus improved the survival of the transplanted CMs.Intramyocardial injection of this hydrogel to the infarcted area of the heart promoted angiogenesis,inhibited fibrosis,and improved cardiac function,exhibiting great potential for MI treatment.展开更多
Endoscopic submucosal dissection(ESD)is a common procedure to treat early and precancerous gastrointestinal lesions.Via submucosal injection,a liquid cushion is created to lift and separate the lesion and malignant pa...Endoscopic submucosal dissection(ESD)is a common procedure to treat early and precancerous gastrointestinal lesions.Via submucosal injection,a liquid cushion is created to lift and separate the lesion and malignant part from the muscular layer where the formed indispensable space is convenient for endoscopic incision.Saline is a most common submucosal injection liquid,but the formed liquid pad lasts only a short time,and thus repeated injections increase the potential risk of adverse events.Hydrogels with high osmotic pressure and high viscosity are used as an alternate;however,with some drawbacks such as tissue damage,excessive injection resistance,and high cost.Here,we reported a nature derived hydrogel of gelatin-oxidized alginate(G-OALG).Based on the rheological analysis and compare to commercial endoscopic mucosal resection(EMR)solution(0.25%hyaluronic acid,HA),a designed G-OALG hydrogel of desired concentration and composition showed higher performances in controllable gelation and injectability,higher viscosity and more stable structures.The G-OALG gel also showed lower propulsion resistance than 0.25%HA in the injection force assessment under standard endoscopic instruments,which eased the surgical operation.In addition,the G-OALG hydrogel showed good in vivo degradability biocompatibility.By comparing the results acquired via ESD to normal saline,the G-OALG shows great histocompatibility and excellent endoscopic injectability,and enables create a longer-lasting submucosal cushion.All the features have been confirmed in the living both pig and rat models.The G-OALG could be a promising submucosal injection agent for esophageal ESD.展开更多
Myocardial infarction(MI)exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species(ROS)and the up-regulation of pro-inflammatory cytokines in the initial stage,and a p...Myocardial infarction(MI)exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species(ROS)and the up-regulation of pro-inflammatory cytokines in the initial stage,and a permanently inadequate blood supply.Herein,an injectable hydrogel fabricated by nanoparticles(NPs)knotted thiolated hyaluronic acid(HA-SH)was reported to reverse the hostile microenvironment and rebuild the heart functions after MI.Inspired by the composite shell-core structure of Ferrero chocolate sphere,a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine(DMOG)NPs core and a thick polydopamine(PDA)shell formed by the self-polymerization of dopamine embedded with watersoluble drug epigallocatechin-3-gallate(EGCG)throughπ-πinteractions.The resulted"Ferrero-like"NPs exhibited a"three-inone"capacity,namely loading two distinct drugs,elimination of ROS,and serving a crosslinker to knot HA-SH."Ferrero-like"NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property,high capability to capture ROS,and programmed release of EGCG and DMOG.Four weeks after deploying the"Ferrero-like"NPs knotted hydrogels into rat infarcted hearts,the ejection fraction(EF)increased by 23.7%,and the infarct size decreased by 21.1%,and the fibrotic area reduced by 24.4%.The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction(RTPCR)demonstrated a down-regulation of inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)),up-regulation of vascular related growth factors(hypoxia inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),von Willebrand factor(vWF),angiopoietin-1(Ang-1))and cardiac-related m RNAs(gap junction protein(Cx43),Cadherin 2).All in all,in this report,a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting"Ferrero-like"NPs knotted hydrogels is developed to reverse hostile microenvironment,with an ability to scavenge ROS,down-regulate pro-inflammation factors in the first stage,and promote angiogenesis in a long term,thereby contributing to a significant improvement of heart functions.展开更多
Injectable hydrogels as an important class of biomaterials have gained much attention in tissue engineering.However,their crosslinking degree is difficult to be controlled after being injected into body.As we all know...Injectable hydrogels as an important class of biomaterials have gained much attention in tissue engineering.However,their crosslinking degree is difficult to be controlled after being injected into body.As we all know,the crosslinking degree strongly influences the physicochemical properties of hydrogels.Therefore,developing an injectable hydrogel with tunable crosslinking degree in vivo is important for tissue engineering.Herein,we present a dual crosslinking strategy to prepare injectable hydrogels with step-by-step tunable crosslinking degree using Schiff base reaction and photopolymerization.The developed hyaluronic acid/poly(y-glutamic acid)(HA/y-PGA)hydrogels exhibit step-by-step tunable swelling behavior,enzymatic degradation behavior and mechanical properties.Mechanical performance tests show that the storage moduli of HA/y-PGA hydrogels are all less than 2000 Pa and the compressive moduli are in kilopascal,which have a good match with soft tissue.In addition,NIH 3T3 cells encapsulated in HA/y-PGA hydrogel exhibit a high cell viability,indicating a good cytocompatibility of HA/y-PGA hydrogel.Therefore,the developed HA/y-PGA hydrogel as an injectable biomaterial has a good potential in soft tissue engineering.展开更多
The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic burden.Tissue engineering technology has become a hot topic in articular cartilage repair as one of the key tr...The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic burden.Tissue engineering technology has become a hot topic in articular cartilage repair as one of the key treatment methods to alleviate OA.Hydrogel,one of the most commonly used scaffold materials,ca n provide a good extracellular matrix microenvironment fo r seed cells such as bone marrow mesenchymal stem cells(BMSCs),which can promote cartilage regeneration.However,the low homing rate of stem cells severely limits their role in promoting articular cartilage regeneration.Stro mal cell-derived factor-1α(SDF-1α) plays a crucial role in the activatio n,mobilization,homing,and migration of MSCs.He rein,a novel injectable chemotaxis hydrogel,composed of chitosan-based injectable hydrogel and embedding SDF-1α-loaded nanodroplets(PFP@NDs-PEG-SDF-1α) was designed and fabricated.The ultrasound was then used to augment the injectable chemotaxis hydrogel and promote the homing migration of BMSCs for OA cartilage repair.The effect of ultrasound augmenting injectable PFP@NDs-PEG-SDF-1α/hydrogel on the migration of BMSCs was verified in vitro and in vivo,which re markably promotes stem cell homing and the repair of cartilage in the OA model.Therefore,the treatment strategy of ultrasound augmenting injectable chemotaxis hydrogel has a bright potential for OA articular cartilage repair.展开更多
Hydrogel stands out as one of the most attractive wound dressings due to its excellent moisturizing properties and capacity to absorb wound exudates.However,conventional hydrogel dressings often lack responsiveness to...Hydrogel stands out as one of the most attractive wound dressings due to its excellent moisturizing properties and capacity to absorb wound exudates.However,conventional hydrogel dressings often lack responsiveness to the microenvironment,merely acting as protective barriers for the wound.Consequently,they exhibit limited effectiveness in preventing infection and facilitating wound repair.To address these problems,we have developed a multifunctional injectable hydrogel,CF/MS@HG,based on peroxidase-like nanozymes,aiming at rapidly healing bacterial-infected wounds.The hydrogel is mainly composed of oxidized sodium alginate,aminated gelatin,and polylysine,encapsulating MIL-101(CuFe)NPs(CF)and manganese selenide nanoparticles(MnSe_(2) NPs,or MS NPs).After injection,the complex rapidly gelatinizes at the infected wound site through a Schiff base reaction.In vitro experiments have demonstrated the hydrogel’s strong adhesion and self-healing capabilities.Moreover,CF exhibiting peroxidase(POD)-like activity,catalyzes in situ hydrogen peroxide(H_(2)O_(2))to generate highly toxic hydroxyl radicals(·OH)within the wound microenvironment,inducing oxidative damage to bacteria.Meanwhile,MS decomposes into H2Se in the slightly acidic wound microenvironment,disrupting bacterial metabolism and inhibiting proliferation.The addition of polylysine further enhances the hydrogel’s antibacterial properties.In vivo experiments have shown that the hydrogel exhibits excellent biological safety and significantly promotes wound healing.This multifunctional smart hydrogel holds great promise for the treatment of bacterial-infected wounds.展开更多
基金supported by Natural Science Foundation of China(No.82202664,82172432,U22A20371)Shenzhen Sustainable Development Project(No.KCXFZ20201221173411031)+4 种基金Shenzhen Science and Technology Program(JCYJ20220818102815033,National Science Foundation of Guangdong Province(No.2021A1515220053,2022A1515010034,2021B1515120061)Guangdong Basic and Applied Basic Research Foundation(No.2019A1515110983,2022A1515012663)Guangzhou Basic and Applied Basic Research Foundation(202102021160)the Fundamental Research Funds for the Central Universities(21624221)the Research Fund Program of Guangdong Provincial Key Laboratory of Speed Capability Research(2023B1212010009).
文摘In clinical settings,regenerating critical-sized calvarial bone defects presents substantial problems owing to the intricacy of surgical methods,restricted bone growth medications,and a scarcity of commercial bone grafts.To treat this life-threatening issue,improved biofunctional grafts capable of properly healing critical-sized bone defects are required.In this study,we effectively created anti-fracture hydrogel systems using spongy-like metal-organic(magnesium-phosphate)coordinated chitosan-modified injectable hydrogels(CPMg)loaded with a bioinspired neobavaisoflavone(NBF)component.The CPMg-NBF hydrogels showed outstanding anti-fracture capabilities during compression testing and retained exceptional mechanical stability even after 28 d of immersion in phosphatebuffered saline.They also demonstrated prolonged and stable release profiles of Mg^(2+)and NBF.Importantly,CPMg-NBF hydrogels revealed robust biphasic mineralization and were non-toxic to MC3T3-E1 cells.To better understand the underlying mechanism of Mg^(2+)and NBF component,as well as their synergistic effect on osteogenesis,we investigated the expression of key osteogenic proteins in the p38 MAPK and NOTCH pathways.Our results showed that CPMg-NBF hydrogels greatly increased the expression of osteogenic proteins(Runx2,OCN,OPN,BMPS and ALP).In vivo experiments showed that the implantation of CPMg-NBF hydrogels resulted in a significant increase in new bone growth within critical-sized calvarial defects.Based on these findings,we expect that the CPMg-NBF supramolecular hydrogel has tremendous promise for use as a therapeutic biomaterial for treating critical-sized calvarial defects.
基金supported by the National Natural Science Foundation of China(No.82102202)Key Research and Development Program Social Development Project of Jiangsu Province(No.BE2023845)Natural Science Foundation of Jiangsu Province(No.BK20210424).
文摘Postoperative recurrence and metastasis are still the main challenges of cancer therapy.Tumor vaccines that induce potent and long-lasting immune activation have great potential for postoperative cancer therapy.However,the clinical effects of therapeutic tumor vaccines are unsatisfactory due to immune escape caused by the lack of immunogenicity after surgery and the local fibrosis barrier of the tumor which limits effector T cell infiltration.To overcome these challenges,we developed an injectable hydrogelbased tumor vaccine,RATG,which contains whole tumor cell lysates(TCL),Toll-like receptor(TLR)7/8 agonist imiquimod(R837)and an antifibrotic drug ARV-825.TCL and R837 were loaded onto the hydrogel to achieve a powerful reservoir of antigens and adjuvants that induced potent and lasting immune activation.More importantly,ARV-825 could be slowly and sustainably released in the tumor resection cavity to downregulateα-smooth muscle actin(α-SMA)and collagen levels,disintegrate fibrosis barriers and promote T cell infiltration after immune activation to reduce immune escape.In addition,ARV-825 also directly acted on the remaining tumor cells to degrade bromodomain-containing protein 4(BRD4)which is a critical epigenetic reader overexpressed in tumor cells,inhibiting tumor cell migration and invasion.Therefore,our injectable hydrogel created a powerful immune niche in postoperative tumor resection cavity,significantly enhancing the efficacy of tumor vaccines.Our strategy potently activates the immune system and disintegrates the fibrotic barrier of residual tumors with immune microenvironment remodeling in situ,showing anti-recurrence and anti-metastatic effects,and provides a new paradigm for postoperative treatment of tumors.
基金supported by the National Key Research and Development Program of China(No.2022YFC2106100)the National Natural Science Foundation of China(No.22078265).
文摘Breast cancer(BC)is a common malignant tumor in women,which seriously affects the health of patients.In this paper,a plasma nano-composite injectable hydrogel CCT@CAD was developed to realize multi-therapy synergistic anti-cancer.In the acidic tumor microenvironment,CCT@CAD released Au-modified cerium dioxide loaded with cisplatin(CAD),and the surface charge of CAD changed from negative to positive based on the pH-responsive charge inversion characteristic,which significantly improved the internalization efficiency and permeability of tumor cells to CAD.The introduction of Au nanoparticles endowed CAD with localized surface plasmon resonance(LSPR)effects.This effect enhanced electron transfer to activate the Ce active site on the surface of cerium dioxide,thus enhancing the activity of nanozyme,which enabled CAD to rapidly produce O2 and consume glutathione in tumor cells.Meanwhile,Au nanoparticles endowed CAD with excellent photothermal conversion ability,and local hyperthermia could be realized under near infrared laser irradiation.Animal experimental results showed that the tumor inhibition rate was nearly 100%after 14-day treatment of CCT@CAD.The combination of chemotherapy,photothermal therapy and nanozyme therapy proposed in this study provides a new idea for the treatment of BC.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20231314)the National Natural Science Foundation of China(No.92168203)+4 种基金the National Key R&D Program of China(No.2022YFA1104300)the Jiangsu Cardiovascular Medicine Innovation Center(No.CXZX202210)the Suzhou“Science and Education Revitalize Health”Youth Science and Technology Project(No.KJXW2021001)the Suzhou“Science and Education Revitalize Health”Youth Science and Technology Project(No.KJXW2021001)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Myocardial infarction (MI) continues to be the primary cause of death globally. Oxidative stress in the initial phase of MI, followed by uncontrolled and excessive myocardial fibrosis, significantly impedes cardiac repair efficiency post-MI, culminating in adverse ventricular remodeling and potential heart failure. To address the diverse pathological stages of MI, an injectable composite hydrogel containing versatile nanoparticles was developed. In this study, mesoporous silicon nanoparticles (MSNs) served as carriers for encapsulating microRNA-29b (miR-29b) mimics with antifibrotic activity, subsequently coated with a complex of natural antioxidant tannic acid and zinc ions (TA/Zn). These nanoparticles were then embedded into a biocompatible alginate hydrogel to enhance retention within the infarcted myocardium. Upon injection into the infarcted region of MI mice, the composite hydrogel gradually released the nanoparticles as it degraded. Initially, the TA/Zn complex on the outer layer scavenged reactive oxygen species, thereby inhibiting cell apoptosis. The subsequent dissociation of the TA/Zn complex led to the release of the encapsulated miR-29b mimics that could inhibit the activation of cardiac fibroblasts and collagen production, thereby alleviating fibrosis progression. Overall, this composite hydrogel demonstrated the potential to reduce infarct size and improve cardiac function, suggesting its promise as a synergistic therapeutic approach for repairing infarcted myocardium.
基金supported by the funding listed as follows:National Natural Science Foundation of China(No.32301115)Sichuan Science and Technology Program(2025ZNSFSC0245)+3 种基金National Key Research and Development Program of China(2023YFC2412802)the Fundamental Research Funds for the Central Universities(2023SCUH0011,No.YJ2021115)Med-X Innovation Programme of Med-X Center of Materials,Sichuan University,China(Grant No.MCMGD202303)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences[CIFMS,(No.2021-I2M-5-013)].
文摘Myocardial infarction(MI)continues to be a leading cause of morbidity and mortality in cardiovascular diseases worldwide,severely compromising cardiac structure and function.While conventional treatments-including pharmacological interventions,coronary artery bypass grafting(CABG),and percutaneous coronary intervention(PCI)-can effectively restore coronary blood flow,their ability to regenerate cardiomyocytes and substantially improve cardiac function remains limited.In this context,injectable hydrogels have emerged as a groundbreaking therapeutic approach,presenting remarkable potential for MI treatment owing to their exceptional biocompatibility,tunable mechanical properties,and versatile functionality.These hydrogels can form stable three-dimensional networks within infarcted myocardium,not only providing mechanical support to mitigate ventricular wall stress but also serving as delivery platforms for bioactive components such as growth factors,therapeutic drugs,and stem cells.Through multiple mechanisms-including attenuation of oxidative stress and calcium overload to protect cardiomyocytes,stimulation of angiogenesis to enhance tissue perfusion,and regulation of inflammatory responses to reduce fibrotic scarring-injectable hydrogels significantly promote myocardial repair and regeneration.Preclinical studies have consistently validated the therapeutic efficacy of various injectable hydrogel formulations in improving cardiac outcomes post-MI,highlighting their transformative potential in cardiovascular medicine.
基金National Natural Science Foundation of China(Nos.22131008 and 21971127)the Haihe Laboratory of Sustainable Chemical Transformations for financial support.
文摘Implantable system maximizes drug concentration and continuously releases drugs near the tumor,which is an effective tool to solve the difficult retention of chemotherapy drugs in bladder cancer.In this work,a novel polysaccharide supramolecular injectable hydrogel(CCA hydrogels for short)is rapidly constructed by simply mixing cationic chitosan,anionic sulfobutyl etherβ-cyclodextrin(SBE-β-CD)and a trace amount of silver ions.The injected hydrogel reconstituted and regained its shape in less than 1 h,and it can still maintain the elasticity suitable for the human body.By packaging the drug directly,the gel achieves a high concentration of doxorubicin,an anticancer drug.Using MB49-luc cells as the model of bladder tumor for anti-tumor in vivo,the CCA-DOX gel has obvious inhibitory effect on bladder tumor,and its inhibitory effect is much greater than that of free DOX.Therefore,this self-healing injectable hydrogel has great potential for in situ treatment of bladder cancer.
基金The Nattional Key Scientific Program-Nanoscience and Nanotechnologygrant number:2009CB930000
文摘To get a sort of new scaffold material for soft tissue reconstruction,we have prepared XLHA-PNIPAAm and XLHA-MC injectable hydrogels through blending crosslinked HA(XLHA) and two temperature-sensitive materials differed in degradation poly(N-isopropylacrylamide)(PNIPAAm) and methylcellulose(MC),respectively.We tested the injectablility,enzymatic biodegradability,temperature-sensitivity,structure cytotoxicity and hemolysis of the two injectable hydrogels.Our research has successfully obtained the preparation condition of XLHA-PNIPAAm injectable hydrogel,and verified that adding non-degradable material PNIPAAm can postpone the degradation of HA more effectively than degradable material MC.PNIPAAm prepared with 5 kGy dose radiation,MBAAm/NIPAAm(M/M)=0.015,monomer concentration=3% produced XLHA-PNIPAAm with slowest enzymatic biodegradability.DSC results showed that temperature-sensitivity of the XLHA-PNIPAAm was more stable than that of XLHA-MC.Two composite hydrogels were qualified in cytotoxicity and hemolysis tests and the biocompatibility of XLHA-PNIPAAm hydrogel showed better than XLHA-MC hydrogel.
基金The authors are very grateful for financial support provided by the National Natural Science Foundation of China(grant No.82302388)Qingdao Natural Science Foundation(grant No.23-2-1-132-zyyd-jch)College Students’Innovative Entrepreneurial Training Plan Program(grant No.S202311065012).
文摘Myocardial infarction(MI)triggers adverse remodeling mechanisms,thus leading to heart failure.Since the applica-tion of biomaterial-based scaffolds emerged as a viable approach for providing mechanical support and promoting cell growth,injectable hydrogels have garnered substantial attention in MI treatment because of their minimally invasive administration through injection and diminished risk of infection.To fully understand the interplay between inject-able hydrogels and infarcted myocardium repair,this review provides an overview of recent advances in injectable hydrogel-mediated MI therapy,including:I)material designs for repairing the infarcted myocardium,considering the pathophysiological mechanism of MI and design principles for biomaterials in MI treatment;II)the development of injectable functional hydrogels for MI treatment,including conductive,self-healing,drug-loaded,and stimulus-responsive hydrogels;and III)research progress in using injectable hydrogels to restore cardiac function in infarcted myocardium by promoting neovascularization,enhancing cardiomyocyte proliferation,decreasing myocardial fibrosis,and inhibiting excessive inflammation.Overall,this review presents the current state of injectable hydrogel research in MI treatment,offering valuable information to facilitate interdisciplinary knowledge transfer and enable the develop-ment of prognostic markers for suitable injectable materials.
基金supported by the National Natural Science Foundation of China(Nos.81960404,81960401 and 82060308)Guizhou Province Science and Technology Project(Nos.[2019]1429 and[2019]2798)+2 种基金Guizhou Provincial People’s Hospital Doctoral Fund(No.GZSYBS[2019]01)Guizhou Provincial People’s Hospital Youth Fund(No.GZSYQN[2019]04)Guizhou Provincial Health Commission Science and Technology Fund(No.gzwkj2021-251).
文摘Current clinical treatments cannot effectively delay the progression of osteoarthritis(OA).Consequently,joint replacement surgery is required for late-stage OA when patients cannot tolerate pain and joint dysfunction.Therefore,the prevention of OA progression in the early and middle stages is an urgent clinical problem.In a previous study,we demonstrated that NDRG3-mediated hypoxic response might be closely related to the development and progression of OA.In this study,an injectable thermosensitive hydrogel was established by cross-linking Pluronic F-127 and hyaluronic acid(HA)for the sustained release of hypoxia-induced exosomes(HExos)derived from adipose-derived mesenchymal stem cells.We demonstrated that for OA at the early and middle stages,the HExos-loaded HP hydrogel could maintain the chondrocyte phenotype by enhancing chondrocyte autophagy,reducing chondrocyte apoptosis,and promoting chondrocyte activity and proliferation through the NDRG3-mediated hypoxic response.This novel composite hydrogel,which could activate the NDRG3-mediated hypoxic response,may provide new ideas and a theoretical basis for the treatment of early-and mid-stage OA.
基金the National Natural Science Founda-tion of China(82220108019 to P.Ji and 82201059 to Q.M.Zhai)the Chongqing Postdoctoral Science Special Foundation(2021XM1031 to Q.M.Zhai)+1 种基金China Postdoctoral Science Foundation(2022M720599 to Q.M.Zhai)Haobo medical technology(Shanghai)limited company helped us synthesize the PEGA materials.
文摘The impaired function of periodontal ligament stem cells(PDLSCs)impedes restoration of periodontal tissues.The cGAS-cGAMP-STING pathway is an innate immune pathway that sensing cytosolic double-stranded DNA(dsDNA),but its role in regulating the function of PDLSCs is still unclear.In this study,we found that mito-chondrial DNA(mtDNA)was released into the cytoplasm through the mitochondrial permeability transition pore(mPTP)in PDLSCs upon inflammation,which binds to cGAS and activated the STING pathway by promoting the production of cGAMP,and ultimately impaired the osteogenic differentiation of PDLSCs.Additionally,it is first found that inflammation can down-regulate the level of the ATP-binding cassette membrane subfamily member C1(ABCC1,a cGAMP exocellular transporter)and ectonucleotide pyrophosphatase/phosphodiesterase 1(ENPP1,a cGAMP hydrolase),which further aggravated the accumulation of intracellular cGAMP,leading to the persistent activation of the cGAS-STING pathway and thus the impaired the differentiation capacity of PDLSCs.Furthermore,we designed a hydrogel system loaded with a mPTP blocker,an ABCC1 agonist and ENPP1 to promote periodontal tissue regeneration by modulating the production,exocytosis,and clearance of cGAMP.In conclusion,our results highlight the profound effects,and specific mechanisms,of the cGAS-STING pathway on the function of stem cells and propose a new strategy to promote periodontal tissue restoration based on the reestablishment of cGAMP homeostasis.
基金supported by the National Natural Science Foundation of China (No. 51973172)Natural Science Foundation of Shaanxi Province (Nos. 2020JC-03 and 2019TD-020)+2 种基金the State Key Laboratory for Mechanical Behavior of Materials,the World-Class Universities (Disciplines) and Characteristic Development Guidance Funds for the Central UniversitiesFundamental Research Funds for the Central Universitiesthe Opening Project of the Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi’an Jiaotong University (No. 2019LHM-KFKT008).
文摘Hydrogels with multifunctionalities,including sufficient bonding strength,injectability and self-healing capacity,responsive-adhesive ability,fault-tolerant and repeated tissue adhesion,are urgently demanded for invasive wound closure and wound healing.Motivated by the adhesive mechanism of mussel and brown algae,bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate(SA),gelatin(GT)and protocatechualdehyde,with ferric ions added,for sutureless post-wound-closure.The dynamic hydrogel cross-linked through Schiff base bond,catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA,endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure,injectability and self-healing capacity,and repeated closure of reopened wounds.Moreover,the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned,which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during surgery.Besides,the hydrogels present good biocompatibility,near-infrared-assisted photothermal antibacterial activity,antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic effect.The in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions,indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant.
文摘The aim of therapeutic neovascularization is to repair ischemic tissues via formation of new blood vessels by delivery of angiogenic growth factors,stem cells or expansion of pre-existing cells.For efficient neovascularization,controlled release of growth factors is particularly necessary since bolus injection of molecules generally lead to a poor outcome due to inadequate retention within the injured site.In this regard,injectable hydrogels,made of natural,synthetic or hybrid biomaterials,have become a promising solution for efficient delivery of angiogenic factors or stem and progenitor cells for in situ tissue repair,regeneration and neovascularization.This review article will broadly discuss the state-of-the-art in the development of injectable hydrogels from natural and synthetic precursors,and their applications in ischemic tissue repair and wound healing.We will cover a wide range of in vitro and in vivo studies in testing the functionalities of the engineered injectable hydrogels in promoting tissue repair and neovascularization.We will also discuss some of the injectable hydrogels that exhibit self-healing properties by promoting neovascularization without the presence of angiogenic factors.
基金the Projects of International Cooperation and Exchanges NSFC(81420108021)Key Program of NSFC(81730067),Excellent Young Scholars NSFC(81622033)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,Jiangsu Provincial Key Medical Talent Foundation and UCLA’s start-up package to Z.G.
文摘Articular cartilage is an important load-bearing tissue distributed on the surface of diarthrodial joints.Due to its avascular,aneural and non-lymphatic features,cartilage has limited self-regenerative properties.To date,the utilization of biomaterials to aid in cartilage regeneration,especially through the use of injectable scaffolds,has attracted considerable attention.Various materials,therapeutics and fabrication approaches have emerged with a focus on manipulating the cartilage microenvironment to induce the formation of cartilaginous structures that have similar properties to the native tissues.In particular,the design and fabrication of injectable hydrogel-based scaffolds have advanced in recent years with the aim of enhancing its therapeutic efficacy and improving its ease of administration.This review summarizes recent progress in these efforts,including the structural improvement of scaffolds,network cross-linking techniques and strategies for controlled release,which present new opportunities for the development of injectable scaffolds for cartilage regeneration.
基金National Natural Science Foundation of China(Nos.82130027,82100963,82270953,81991505 and 81921002)Shanghai Rising-Star Program(21QA1405400)+1 种基金Natural Science Foundation of Shanghai(22ZR1436400)Innovative Research Team of High-Level Local Universities in Shanghai.
文摘Injectable hydrogel is suitable for the repair of lacunar bone deficiency.This study fabricated an injectable,self-adaptive silk fibroin/mesoporous bioglass/sodium alginate(SMS)composite hydrogel system.With controllable and adjustable physical and chemical properties,the SMS hydrogel could be easily optimized adaptively to different clinical applications.The SMS hydrogel effectively showed great injectability and shapeability,allowing defect filling with no gap.Moreover,the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation,responsive to the concentration of Ca2+and inflammatory-like pH value in the microenvi-ronment of bone deficiency,respectively.In vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling pathway.The SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial cells.Investigations of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2,which could create a specific favorable environment to induce new bone formation and angiogenesis.Meanwhile,SMS hydrogel was proved to be antibacterial,especially for gram-negative bacteria.Furthermore,in vivo study indicated that SMS could be easily applied for maxillary sinus elevation,inducing sufficient new bone formation.Thus,it is convincing that SMS hydrogel could be potent in a simple,minimally invasive and efficient treatment for the repair of lacunar bone deficiency.
基金financially supported by the National Natural Science Foundation of China (Nos.92168203 and 22175125)the Extracurricular Scientific Research Project for Students of Suzhou Medical College of Soochow University (No.2021YXBKWKY070)+3 种基金the Scientific Research Innovation Project for Graduate Students of Jiangsu Province (No.KYCX22_3189)the Introduction Project of Clinical Medicine Expert Team for Suzhou (No.SZYJTD201704)the Natural Science Foundation of the Jiangsu Higher Education Insti-tutions of China (No.21KJA150008)the Priority Academic Pro-gram Development of Jiangsu Higher Education Institutions (PAPD).
文摘Myocardial infarction(MI)is one of the typical cardiovascular diseases,which persist as the leading cause of death globally.Due to the poor regenerative capability of endogenous cardiomyocytes(CMs),the transplantation of exogenous CMs becomes a promising option for MI treatment.However,the low retention and survival of transplanted cells still limit the clinical translation of cell therapy.Herein,an alginate/fibrin-based injectable hydrogel was prepared for the delivery of neonatal CMs and an angiogen-esis agent vascular endothelial growth factor(VEGF)locally to the infarcted area of the heart.This hydro-gel combined the specific advantages of alginate and fibrin with proper mechanical properties and cell affinity,showing good biocompatibility to support the retention and integration of the transplanted CMs to the host myocardium.Moreover,the delivered VEGF was favorable for the blood recovery to mitigate the ischemic microenvironment of the infarcted area and thus improved the survival of the transplanted CMs.Intramyocardial injection of this hydrogel to the infarcted area of the heart promoted angiogenesis,inhibited fibrosis,and improved cardiac function,exhibiting great potential for MI treatment.
基金the the National Science Foundation of China(No.81802982)ChongQing Science&Technology Commission Fund(No.CSTC2018jcyjAX0102).
文摘Endoscopic submucosal dissection(ESD)is a common procedure to treat early and precancerous gastrointestinal lesions.Via submucosal injection,a liquid cushion is created to lift and separate the lesion and malignant part from the muscular layer where the formed indispensable space is convenient for endoscopic incision.Saline is a most common submucosal injection liquid,but the formed liquid pad lasts only a short time,and thus repeated injections increase the potential risk of adverse events.Hydrogels with high osmotic pressure and high viscosity are used as an alternate;however,with some drawbacks such as tissue damage,excessive injection resistance,and high cost.Here,we reported a nature derived hydrogel of gelatin-oxidized alginate(G-OALG).Based on the rheological analysis and compare to commercial endoscopic mucosal resection(EMR)solution(0.25%hyaluronic acid,HA),a designed G-OALG hydrogel of desired concentration and composition showed higher performances in controllable gelation and injectability,higher viscosity and more stable structures.The G-OALG gel also showed lower propulsion resistance than 0.25%HA in the injection force assessment under standard endoscopic instruments,which eased the surgical operation.In addition,the G-OALG hydrogel showed good in vivo degradability biocompatibility.By comparing the results acquired via ESD to normal saline,the G-OALG shows great histocompatibility and excellent endoscopic injectability,and enables create a longer-lasting submucosal cushion.All the features have been confirmed in the living both pig and rat models.The G-OALG could be a promising submucosal injection agent for esophageal ESD.
基金This work was supported by the Excellent Young Scientists Fund by National Natural Science Foundation of China(Grant No.31822020)the National Natural Science Foundation of China(Grant Nos.31771030&31870965)+1 种基金the National Key Research and Development Program of China(Grant No.2016YFC1101301)and Tianjin Outstanding Youth Science Foundation(Grant No.17JCJQJC46200).
文摘Myocardial infarction(MI)exhibits a complicated and ever-accelerated pathological change involving excessive reactive oxygen species(ROS)and the up-regulation of pro-inflammatory cytokines in the initial stage,and a permanently inadequate blood supply.Herein,an injectable hydrogel fabricated by nanoparticles(NPs)knotted thiolated hyaluronic acid(HA-SH)was reported to reverse the hostile microenvironment and rebuild the heart functions after MI.Inspired by the composite shell-core structure of Ferrero chocolate sphere,a mimetic nanocarrier was designed to consist of the hydrophobic dimethyloxalylglycine(DMOG)NPs core and a thick polydopamine(PDA)shell formed by the self-polymerization of dopamine embedded with watersoluble drug epigallocatechin-3-gallate(EGCG)throughπ-πinteractions.The resulted"Ferrero-like"NPs exhibited a"three-inone"capacity,namely loading two distinct drugs,elimination of ROS,and serving a crosslinker to knot HA-SH."Ferrero-like"NPs and HA-SH could rapidly form a hydrogel that exhibited a stable mechanical property,high capability to capture ROS,and programmed release of EGCG and DMOG.Four weeks after deploying the"Ferrero-like"NPs knotted hydrogels into rat infarcted hearts,the ejection fraction(EF)increased by 23.7%,and the infarct size decreased by 21.1%,and the fibrotic area reduced by 24.4%.The outcomes of immunofluorescence staining and reverse transcription-polymerase chain reaction(RTPCR)demonstrated a down-regulation of inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)),up-regulation of vascular related growth factors(hypoxia inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),von Willebrand factor(vWF),angiopoietin-1(Ang-1))and cardiac-related m RNAs(gap junction protein(Cx43),Cadherin 2).All in all,in this report,a very simple approach to intertemporally address the intricate and ongoing pathological changes after MI by injecting"Ferrero-like"NPs knotted hydrogels is developed to reverse hostile microenvironment,with an ability to scavenge ROS,down-regulate pro-inflammation factors in the first stage,and promote angiogenesis in a long term,thereby contributing to a significant improvement of heart functions.
基金the National Natural Science Foundation of China(No.31771049)Foundation of key R&D Project of Jiangsu Province(No.BE2018731)+1 种基金Research Foundation of State Key Laboratory of Materials-Oriented Chemical Engineering(Nos.ZK201806 and No.KLI 8-06)the Six Talent Peaks Project of Jiangsu Province(No.SWYY-046)。
文摘Injectable hydrogels as an important class of biomaterials have gained much attention in tissue engineering.However,their crosslinking degree is difficult to be controlled after being injected into body.As we all know,the crosslinking degree strongly influences the physicochemical properties of hydrogels.Therefore,developing an injectable hydrogel with tunable crosslinking degree in vivo is important for tissue engineering.Herein,we present a dual crosslinking strategy to prepare injectable hydrogels with step-by-step tunable crosslinking degree using Schiff base reaction and photopolymerization.The developed hyaluronic acid/poly(y-glutamic acid)(HA/y-PGA)hydrogels exhibit step-by-step tunable swelling behavior,enzymatic degradation behavior and mechanical properties.Mechanical performance tests show that the storage moduli of HA/y-PGA hydrogels are all less than 2000 Pa and the compressive moduli are in kilopascal,which have a good match with soft tissue.In addition,NIH 3T3 cells encapsulated in HA/y-PGA hydrogel exhibit a high cell viability,indicating a good cytocompatibility of HA/y-PGA hydrogel.Therefore,the developed HA/y-PGA hydrogel as an injectable biomaterial has a good potential in soft tissue engineering.
基金This work was financially sponsored by the National Natural Science Foundation of China(Nos.81971622,81671696,82071938,and 51703141)Sichuan Science and Technology Program(Nos.2019YFS0219,2020YFH0087,and 2020YJ0055)the Post-Doctor Research Project,West China Hospital,Sichuan University(No.2018HXBH077).
文摘The increasing incidence of osteoarthritis(OA) seriously affects life quality,posing a huge socioeco nomic burden.Tissue engineering technology has become a hot topic in articular cartilage repair as one of the key treatment methods to alleviate OA.Hydrogel,one of the most commonly used scaffold materials,ca n provide a good extracellular matrix microenvironment fo r seed cells such as bone marrow mesenchymal stem cells(BMSCs),which can promote cartilage regeneration.However,the low homing rate of stem cells severely limits their role in promoting articular cartilage regeneration.Stro mal cell-derived factor-1α(SDF-1α) plays a crucial role in the activatio n,mobilization,homing,and migration of MSCs.He rein,a novel injectable chemotaxis hydrogel,composed of chitosan-based injectable hydrogel and embedding SDF-1α-loaded nanodroplets(PFP@NDs-PEG-SDF-1α) was designed and fabricated.The ultrasound was then used to augment the injectable chemotaxis hydrogel and promote the homing migration of BMSCs for OA cartilage repair.The effect of ultrasound augmenting injectable PFP@NDs-PEG-SDF-1α/hydrogel on the migration of BMSCs was verified in vitro and in vivo,which re markably promotes stem cell homing and the repair of cartilage in the OA model.Therefore,the treatment strategy of ultrasound augmenting injectable chemotaxis hydrogel has a bright potential for OA articular cartilage repair.
基金supported by the National Natural Science Foundation of China(Grant No.52102353)the Natural Science Foundation of Zhejiang Province(Grant No.LQ22E030018)+1 种基金the Fundamental Research Funds of Tongxiang Research Institute of Zhejiang Sci-Tech University(Grant No.TYY202212)the Key Research&Development Program of Zhejiang Province(Grant Nos.2021C01180 and 2019C04020).
文摘Hydrogel stands out as one of the most attractive wound dressings due to its excellent moisturizing properties and capacity to absorb wound exudates.However,conventional hydrogel dressings often lack responsiveness to the microenvironment,merely acting as protective barriers for the wound.Consequently,they exhibit limited effectiveness in preventing infection and facilitating wound repair.To address these problems,we have developed a multifunctional injectable hydrogel,CF/MS@HG,based on peroxidase-like nanozymes,aiming at rapidly healing bacterial-infected wounds.The hydrogel is mainly composed of oxidized sodium alginate,aminated gelatin,and polylysine,encapsulating MIL-101(CuFe)NPs(CF)and manganese selenide nanoparticles(MnSe_(2) NPs,or MS NPs).After injection,the complex rapidly gelatinizes at the infected wound site through a Schiff base reaction.In vitro experiments have demonstrated the hydrogel’s strong adhesion and self-healing capabilities.Moreover,CF exhibiting peroxidase(POD)-like activity,catalyzes in situ hydrogen peroxide(H_(2)O_(2))to generate highly toxic hydroxyl radicals(·OH)within the wound microenvironment,inducing oxidative damage to bacteria.Meanwhile,MS decomposes into H2Se in the slightly acidic wound microenvironment,disrupting bacterial metabolism and inhibiting proliferation.The addition of polylysine further enhances the hydrogel’s antibacterial properties.In vivo experiments have shown that the hydrogel exhibits excellent biological safety and significantly promotes wound healing.This multifunctional smart hydrogel holds great promise for the treatment of bacterial-infected wounds.
