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
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
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
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
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
Photodynamic therapy(PDT)has been emerged as a promising modality for cancer treatment.However,the development of drug delivery system enabling continuous release of photosensitizers(PSs)for long-term PDT treatment st...Photodynamic therapy(PDT)has been emerged as a promising modality for cancer treatment.However,the development of drug delivery system enabling continuous release of photosensitizers(PSs)for long-term PDT treatment still remains challenges.Herein,a H_(2)O_(2)-responsive injectable hydrogel,covalently crosslinked by N^(1)-(4-boronobenzyl)-N^(3)-(4-boronophenyl)-N^(1),N^(1),N^(3),N^(3)-tetramethylpropane-1,3-diaminium(TSPBA)with PVA containing polythiophene quaternary ammonium salt(PT2)polymer dots(PDots)as a photosensitizer was fabricated.Under the stimulation of H_(2)O_(2),the obtained injectable hydrogel gradually degrades and releases PDots.In vitro experiments suggested that the released PDots could realize efficient tumor cells inhibition through its robust singlet oxygen generation capability upon 577 nm laser irradiation.In vivo studies demonstrated a sustained retention of PDots for at least 7 days following single-dose administration,facilitating efficient tumor inhibition with light treatments for 3 times without apparent biotoxicity.This work presents an innovative polymer dots-based composite local drug delivery system for long-term PDT in cancer treatment.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
Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in ...Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in additional treatment morbidity and even threaten the lives of patients.Thus,designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge.Herein,a series of injectable pH-responsive selfhealing adhesive hydrogels based on acryloyl-6-aminocaproic acid(AA)and AA-g-N-hydroxysuccinimide(AA-NHS)were developed,and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model.The hydrogels showed a suitable gelation time,an autonomous and efficient self-healing capacity,hemostatic properties,and good biocompatibility.With the introduction of AA-NHS as a micro-cross-linker,the hydrogels exhibited enhanced adhesive strength.A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding.A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition,α-SMA expression,and blood vessel formation.These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.展开更多
Baicalin,extracted from traditional Chinese medicine Scutellaria baicalensis Georg,possesses multiple pharmacological activities and has great potential for chronic skin wound repair.However,the poor solubility and la...Baicalin,extracted from traditional Chinese medicine Scutellaria baicalensis Georg,possesses multiple pharmacological activities and has great potential for chronic skin wound repair.However,the poor solubility and lack of suitable vehicles greatly limit its further application.Herein,we proposed a convenient and robust strategy,employing PBS solution as solvent,to enhance the solubility of baicalin.Furthermore,we constructed injectable baicalin/F127 hydrogels to study their application in skin wound treatment.The composition and temperature sensitivity of baicalin/Pluronic®F-127 hydrogels were confirmed by FTIR and rheological testing,respectively.In vitro release measurement indicated that the first order model was best fitted with the release profile of baicalin from hydrogel matrix.Besides,MTT assay,AO/EO staining assay as well as hemolytic activity test revealed the excellent cytocompatibility of baicalin/F127 hydrogels.Antioxidant activity assay demonstrated the cytoprotective activity of baicalin/F127 hydrogels against reactive oxygen species(ROS).Furthermore,the in vivo experiments exhibited the ability of baicalin/F127 hydrogel to accelerate wound healing.In conclusion,this novel injectable baicalin/F127 hydrogel should have bright application for chronic wound treatment.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
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
The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles...The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles(CuS NPs)and pH-sensitive doxorubicin-loaded zeolitic imidazolate frameworks nanoparticles(DOX@ZIF-8 NPs)were prepared and could be well-dispersed into the hydrogel system.The presence of CuS NPs can achieve photothermal therapy(PTT)for tumors under the irradiation of the near-infrared(NIR)laser.Moreover,CuS NPs can generate photodynamic effects under NIR irradiation,converting oxygen into toxic reactive oxygen species(ROS)and presenting efficient photodynamic therapy(PDT).The DOX@ZIF-8 NPs can be decomposed under an intracellular acidic environment and realize the controlled release of DOX.The injectable self-healing hydrogel loading Cu S and DOX@ZIF-8 NPs can achieve synergistic photothermal-photodynamic-chemo therapy for tumors and will inspire the researchers to construct a platform from hydrogel combined with multifunctional nanomaterials to realize the effective multimodal therapy for tumor.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
A luminescent and injectable supramolecular hydrogel was successfully constructed through the non- covalent cross-linking of polymers mediated by tetraphenylethylene-bridged cyclodextrin oligomers, presenting the stro...A luminescent and injectable supramolecular hydrogel was successfully constructed through the non- covalent cross-linking of polymers mediated by tetraphenylethylene-bridged cyclodextrin oligomers, presenting the strong blue fluorescence, the reversible gelation behavior responsive to various external stimuli and the good mechanical property of shear thinning.展开更多
Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self...Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self-healing nano hybrid hydrogel was on-demand prepared via a fast(within 30 s)and easy gelation approach by reversible Schiff base formed between-CH=O of oxidized sodium alginate(OSA)and-NH2 of glycol chitosan(GCS)mixed with calcium phosphate nanoparticles(CaP NPs).Its raw materials can be ready in large quantities by a simple synthesis process.The mechanical strength,degradation and swelling behavior of the hydrogel can be readily controlled by simply controlling the molar ratio of-CH=O and-NH2.This hydrogel exhibits pH responsiveness,good degradability and biocompatibility.The hydrogel used as the matrix for mesenchymal stem cells can significantly induce the proliferation,differentiation and osteoinduction in vitro.These results showed this novel hydrogel is an ideal candidate for applications in bone tissue regeneration and drug delivery.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
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
A novel injectable hydrogel that was synthesized by in situ crosslinking of hyaluronan and polyvinyl phosphonic acid was proposed in this study. Fourier transform infrared spectrum (FT-IR) analysis, scanning electron ...A novel injectable hydrogel that was synthesized by in situ crosslinking of hyaluronan and polyvinyl phosphonic acid was proposed in this study. Fourier transform infrared spectrum (FT-IR) analysis, scanning electron microscope (SEM), pH measurement, and biodegradation test were used to confirm its characteristics. The results permitted to prove successful crosslinking, observe the inner morphology of hydrogel and pore sizes distribution, and determine the decomposition of hydrogel components during incubation time. Result of pH measurement showed that the pH scale of hydrogel decreased when volume of PVPA increased. As a consequence, it affected the cytotoxicity value, cell proliferation, and cell growth behaviors of each hydrogel. Optical microscope observation showed that chondroblasts cell proliferated well on HA-PVPA hydrogel. Therefore, these results suggest that the new injectable hydrogel is appropriate for bone/cartilage regeneration applications.展开更多
A kind of novel copolymer hydrogel of poly（N, N-dimethylaminoethyl methacrylate-co-N-isopropylacrylamide） （poly[DMAEMA/NIPAAm]） was synthesized by the initiation of K2S2O8, N, N＇-methylene-bis（acrylamide） （Bis...A kind of novel copolymer hydrogel of poly（N, N-dimethylaminoethyl methacrylate-co-N-isopropylacrylamide） （poly[DMAEMA/NIPAAm]） was synthesized by the initiation of K2S2O8, N, N＇-methylene-bis（acrylamide） （Bis） was used as the crosslinker. The effects of monomer content, pH and temperature on swelling ratio of the hydrogel were investigated; the thermo-sensitivity in deionized water and in physiological saline was determined. It showed that the swelling ratio of the hydrogel could be changed by changing the temperature or pH alternately. Both swelling ratio and LCST （Lower Critical Solution Temperature） of the hydrogel decreased with the increase of NIPAAm in the co-polymer content.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 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financially supported by the National Natural Science Foundation of China(Nos.52272052 and 51972315)。
文摘Photodynamic therapy(PDT)has been emerged as a promising modality for cancer treatment.However,the development of drug delivery system enabling continuous release of photosensitizers(PSs)for long-term PDT treatment still remains challenges.Herein,a H_(2)O_(2)-responsive injectable hydrogel,covalently crosslinked by N^(1)-(4-boronobenzyl)-N^(3)-(4-boronophenyl)-N^(1),N^(1),N^(3),N^(3)-tetramethylpropane-1,3-diaminium(TSPBA)with PVA containing polythiophene quaternary ammonium salt(PT2)polymer dots(PDots)as a photosensitizer was fabricated.Under the stimulation of H_(2)O_(2),the obtained injectable hydrogel gradually degrades and releases PDots.In vitro experiments suggested that the released PDots could realize efficient tumor cells inhibition through its robust singlet oxygen generation capability upon 577 nm laser irradiation.In vivo studies demonstrated a sustained retention of PDots for at least 7 days following single-dose administration,facilitating efficient tumor inhibition with light treatments for 3 times without apparent biotoxicity.This work presents an innovative polymer dots-based composite local drug delivery system for long-term PDT in cancer treatment.
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This work was jointly supported by the National Natural Science Foundation of China(grant Nos.:51973172,51673155,81201927,82002957 and 81672460)the National Key Research and Development Plan of China(No.2018YFC0115300)+5 种基金the State Key Laboratory for Mechanical Behavior of Materials,the World-Class Universities(Disciplines)the Characteristic Development Guidance Funds for the Central Universities,the Natural Science Foundation of Shaanxi Province(No.2020JC-03 and 2019TD-020)the Innovation Talent Promotion Plan of Shaanxi(No.2017KJXX-07)the Key Research and Development Program of Shaanxi Province(No.2019SF-012)the Opening Project of Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi’an Jiaotong University(No.2019LHM-KFKT008)Fundamental Research Funds for the Central Universities of China(No.xjj2018090).
文摘Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in additional treatment morbidity and even threaten the lives of patients.Thus,designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge.Herein,a series of injectable pH-responsive selfhealing adhesive hydrogels based on acryloyl-6-aminocaproic acid(AA)and AA-g-N-hydroxysuccinimide(AA-NHS)were developed,and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model.The hydrogels showed a suitable gelation time,an autonomous and efficient self-healing capacity,hemostatic properties,and good biocompatibility.With the introduction of AA-NHS as a micro-cross-linker,the hydrogels exhibited enhanced adhesive strength.A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding.A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition,α-SMA expression,and blood vessel formation.These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.
基金the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2018ZX10301402)International Cooperation and Exchange of the National Natural Science Foundation of China(No.51820105004)+3 种基金Science and Technology Program of Guangzhou(No.201707010094)Guangdong Innovative and Entrepreneurial Research Team Program(Nos.2013S086 and 2016ZT06S029)Science and Technology Planning Project of Shenzhen(Nos.JCYJ20170307141438157 and JCYJ20180307163534533)Fundamental Research Funds for the Central Universities(No.191gpy209)。
文摘Baicalin,extracted from traditional Chinese medicine Scutellaria baicalensis Georg,possesses multiple pharmacological activities and has great potential for chronic skin wound repair.However,the poor solubility and lack of suitable vehicles greatly limit its further application.Herein,we proposed a convenient and robust strategy,employing PBS solution as solvent,to enhance the solubility of baicalin.Furthermore,we constructed injectable baicalin/F127 hydrogels to study their application in skin wound treatment.The composition and temperature sensitivity of baicalin/Pluronic®F-127 hydrogels were confirmed by FTIR and rheological testing,respectively.In vitro release measurement indicated that the first order model was best fitted with the release profile of baicalin from hydrogel matrix.Besides,MTT assay,AO/EO staining assay as well as hemolytic activity test revealed the excellent cytocompatibility of baicalin/F127 hydrogels.Antioxidant activity assay demonstrated the cytoprotective activity of baicalin/F127 hydrogels against reactive oxygen species(ROS).Furthermore,the in vivo experiments exhibited the ability of baicalin/F127 hydrogel to accelerate wound healing.In conclusion,this novel injectable baicalin/F127 hydrogel should have bright application for chronic wound treatment.
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.
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 National Natural Science Foundation of China(No.82172040)。
文摘The injectable self-healing polysaccharide hydrogel was prepared by the formation of Schiff base bonds between aldehyde-modified methylcellulose(MC–CHO)and carboxymethyl chitosan(CMC).The copper sulfide nanoparticles(CuS NPs)and pH-sensitive doxorubicin-loaded zeolitic imidazolate frameworks nanoparticles(DOX@ZIF-8 NPs)were prepared and could be well-dispersed into the hydrogel system.The presence of CuS NPs can achieve photothermal therapy(PTT)for tumors under the irradiation of the near-infrared(NIR)laser.Moreover,CuS NPs can generate photodynamic effects under NIR irradiation,converting oxygen into toxic reactive oxygen species(ROS)and presenting efficient photodynamic therapy(PDT).The DOX@ZIF-8 NPs can be decomposed under an intracellular acidic environment and realize the controlled release of DOX.The injectable self-healing hydrogel loading Cu S and DOX@ZIF-8 NPs can achieve synergistic photothermal-photodynamic-chemo therapy for tumors and will inspire the researchers to construct a platform from hydrogel combined with multifunctional nanomaterials to realize the effective multimodal therapy for tumor.
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the National Natural Science Foundation of China (Nos. 21432004,21672113 and 91527301)for financial support
文摘A luminescent and injectable supramolecular hydrogel was successfully constructed through the non- covalent cross-linking of polymers mediated by tetraphenylethylene-bridged cyclodextrin oligomers, presenting the strong blue fluorescence, the reversible gelation behavior responsive to various external stimuli and the good mechanical property of shear thinning.
基金supported by the National Key Research and Development Program of China(No.2017YFC1104102)National Natural Science Foundation of China(Nos.31370958,21875044)+1 种基金Key Program of Natural Science Foundation of Fujian Province(No.2018Y0056)the International Scientific Partnership Program ISPP at King Saud University for funding this research work through ISPP-17-94(2)。
文摘Injectable hydrogels have been considered as promising materials for bone regeneration,but their osteoinduction and mechanical performance are yet to be improved.In this study,a novel biocompatible injectable and self-healing nano hybrid hydrogel was on-demand prepared via a fast(within 30 s)and easy gelation approach by reversible Schiff base formed between-CH=O of oxidized sodium alginate(OSA)and-NH2 of glycol chitosan(GCS)mixed with calcium phosphate nanoparticles(CaP NPs).Its raw materials can be ready in large quantities by a simple synthesis process.The mechanical strength,degradation and swelling behavior of the hydrogel can be readily controlled by simply controlling the molar ratio of-CH=O and-NH2.This hydrogel exhibits pH responsiveness,good degradability and biocompatibility.The hydrogel used as the matrix for mesenchymal stem cells can significantly induce the proliferation,differentiation and osteoinduction in vitro.These results showed this novel hydrogel is an ideal candidate for applications in bone tissue regeneration and drug delivery.
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(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.
文摘A novel injectable hydrogel that was synthesized by in situ crosslinking of hyaluronan and polyvinyl phosphonic acid was proposed in this study. Fourier transform infrared spectrum (FT-IR) analysis, scanning electron microscope (SEM), pH measurement, and biodegradation test were used to confirm its characteristics. The results permitted to prove successful crosslinking, observe the inner morphology of hydrogel and pore sizes distribution, and determine the decomposition of hydrogel components during incubation time. Result of pH measurement showed that the pH scale of hydrogel decreased when volume of PVPA increased. As a consequence, it affected the cytotoxicity value, cell proliferation, and cell growth behaviors of each hydrogel. Optical microscope observation showed that chondroblasts cell proliferated well on HA-PVPA hydrogel. Therefore, these results suggest that the new injectable hydrogel is appropriate for bone/cartilage regeneration applications.
文摘A kind of novel copolymer hydrogel of poly（N, N-dimethylaminoethyl methacrylate-co-N-isopropylacrylamide） （poly[DMAEMA/NIPAAm]） was synthesized by the initiation of K2S2O8, N, N＇-methylene-bis（acrylamide） （Bis） was used as the crosslinker. The effects of monomer content, pH and temperature on swelling ratio of the hydrogel were investigated; the thermo-sensitivity in deionized water and in physiological saline was determined. It showed that the swelling ratio of the hydrogel could be changed by changing the temperature or pH alternately. Both swelling ratio and LCST （Lower Critical Solution Temperature） of the hydrogel decreased with the increase of NIPAAm in the co-polymer content.
