Study on Preparation of Temperature-sensitive Injectable Hydrogel

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.

Polysaccharide based supramolecular injectable hydrogels for in situ treatment of bladder cancer

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.

Decellularised extracellular matrix-based injectable hydrogels for tissue engineering applications

Decellularised extracellular matrix(dECM)is a biomaterial derived from natural tissues that has attracted considerable attention from tissue engineering researchers due to its exceptional biocompatibility and malleability attributes.These advantageous properties often facilitate natural cell infiltration and tissue reconstruction for regenerative medicine.Due to their excellent fluidity,the injectable hydrogels can be administered in a liquid state and subsequently formed into a gel state in vivo,stabilising the target area and serving in a variety of ways,such as support,repair,and drug release functions.Thus,dECM-based injectable hydrogels have broad prospects for application in complex organ structures and various tissue injury models.This review focuses on exploring research advances in dECM-based injectable hydrogels,primarily focusing on the applications and prospects of dECM hydrogels in tissue engineering.Initially,the recent developments of the dECM-based injectable hydrogels are explained,summarising the different preparation methods with the evaluation of injectable hydrogel properties.Furthermore,some specific examples of the applicability of dECM-based injectable hydrogels are presented.Finally,we summarise the article with interesting prospects and challenges of dECM-based injectable hydrogels,providing insights into the development of these composites in tissue engineering and regenerative medicine.

Promoting lacunar bone regeneration with an injectable hydrogel adaptive to the microenvironment

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.

Thermosensitive injectable hydrogel loaded with hypoxia-induced exosomes maintains chondrocyte phenotype through NDRG3-mediated hypoxic response

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.

Bioinspired Injectable Self-Healing Hydrogel Sealant with Fault-Tolerant and Repeated Thermo-Responsive Adhesion for Sutureless Post-Wound-Closure and Wound Healing

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.

Advances of injectable hydrogel-based scaffolds for cartilage regeneration

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.

Therapeutic neovascularization promoted by injectable hydrogels

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.

Viscosity and degradation controlled injectable hydrogel for esophageal endoscopic submucosal dissection

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.

“Ferrero-like”nanoparticles knotted injectable hydrogels to initially scavenge ROS and lastingly promote vascularization in infarcted hearts

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.

Injectable hydrogels for spinal cord injury repair

Spinal cord injury(SCI)often causes severe functional impairment of body,which leads to a huge burden to the patient and the whole society.Many strategies,especially biomaterials,have been employed for SCI repair.Among various biomaterials,injectable hydrogels have attracted much attention because of their ability to load functional components and be injected into the lesioned area without surgeries.In this review,we summarize the recent progress in injectable hydrogels for SCI repair.We firstly introduce the pathophysiology of SCI,which reveals the mechanism of clinical manifestations and determines the therapeutic schedule.Then,we describe the original sources of polymers and the crosslinking manners in forming hydrogels.After that,we focus on the in vivo therapeutic strategies and effects of injectable hydrogels.Finally,the recent challenges and future outlook of injectable hydrogel for SCI repair are concluded and discussed.We believe this review can be helpful and inspire the further development of injectable hydrogels for SCI repair.

Preparation and Evaluation of an Injectable Chitosan-Hyaluronic Acid hydrogel for Peripheral Nerve Regeneration

The aim of this study was to obtain the fillers in the lumen of hollow nerve conduits（NCs） to improve the microenvironment of nerve regeneration. A p H-induced injectable chitosan（CS）-hyaluronic acid（HA） hydrogel for nerve growth factor（NGF） sustained release was developed. Its properties were characterized by gelation time, FT-IR, SEM, in vitro swelling and degradation. Furthermore, the in vitro NGF release profiles and cell biocompatibility were also investigated. The experimental results show that the CS-HA aqueous solution can undergo a rapid gelation 3 minutes after its environmental p H is changed to 7.4. The CSHA hydrogel has interconnected channels with a controllable pore diameter and with a porosity of about 80%. It has a favorable swelling behavior and can be degraded by about 70% within 8 weeks in vitro and is suitable for NGF release. The CS-HA/NGF hydrogel exhibits a lower cytotoxicity and is in favor of the adhesion and proliferation of the BMMSCs cells. It is indicated that the CS-HA/NGF will be a promising candidate for neural tissue engineering.

Injectable Self‑Healing Adhesive pH‑Responsive Hydrogels Accelerate Gastric Hemostasis and Wound Healing

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.

Alkaline activation of endogenous latent TGFβ1 by an injectable hydrogel directs cell homing for in situ complex tissue regeneration

Utilization of the body’s regenerative potential for tissue repair is known as in situ tissue regeneration.However,the use of exogenous growth factors requires delicate control of the dose and delivery strategies and may be accompanied by safety,efficacy and cost concerns.In this study,we developed,for the first time,a biomaterial-based strategy to activate endogenous transforming growth factor beta 1(TGFβ1)under alkaline conditions for effective in situ tissue regeneration.We demonstrated that alkaline-activated TGFβ1 from blood serum,bone marrow fluids and soaking solutions of meniscus and tooth dentin was capable of increasing cell recruitment and early differentiation,implying its broad practicability.Furthermore,we engineered an injectable hydrogel(MS-Gel)consisting of gelatin microspheres for loading strong alkaline substances and a modified gelatin matrix for hydrogel click crosslinking.In vitro models showed that alkaline MS-Gel controllably and sustainably activated endogenous TGFβ1 from tooth dentin for robust bone marrow stem cell migration.More importantly,infusion of in vivo porcine prepared root canals with alkaline MS-Gel promoted significant pulp-dentin regeneration with neurovascular stroma and mineralized tissue by endogenous proliferative cells.Therefore,this work offers a new bench-to-beside translation strategy using biomaterial-activated endogenous biomolecules to achieve in situ tissue regeneration without the need for cell or protein delivery.

Injectable“cocktail”hydrogel with dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic effect

The combination of the first-line standard chemotherapeutic drug doxorubicin hydrochloride(DOX)and the molecular-targeted drug Herceptin(HCT)has emerged as a promising strategy for human epidermal growth receptor 2(HER-2)overexpressing breast cancer treatment.However,insufficient drug accumulation and severe cardiotoxicity are two major challenges that limit its clinical application.Herein,an in situ forming gold nanorods(AuNRs)-sodium alginate(ALG)hybrid hydrogel encapsulating DOX and HCT was engineered for tumor synergistic therapy involving injectable,dual-stimuli-responsive drug release,photothermal ablation,and drug-antibody synergistic therapy.The photothermal agent AuNRs,anticancer drug DOX,and anticancer antibody HCT were mixed in ALG solution,and after injection,the soluble ALG was quickly transformed into a hydrogel in the presence of Ca^(2+)in the body.Significantly,the hybrid hydrogel exhibits an extremely high photothermal conversion efficiency of 70%under 808 nm laser irradiation.The thermal effect can also provide photothermal stimulation to trigger the drug release from the gel matrix.In addition,the drug release rate and the releasing degree are also sensitive to the pH.In vitro studies demonstrated that the PEI-AuNR/DOX/HCT/ALG hydrogel has facilitated the therapeutic efficiency of each payload and demonstrated a strong synergistic killing effect on SK-BR-3 cells.In vivo imaging results showed that the local drug delivery system can effectively reduce the nonspecific distribution in normal tissues and increase drug concentration at tumor sites.The proposed hydrogel system shows significant clinical implications by easily introducing a sustainable photothermal therapy and a potential universal carrier for the local delivery of multiple drugs to overcome the challenges faced in HER-2 overexpressing cancer therapy.

Orthopedic revolution:The emerging role of nanotechnology

This review summarizes the latest progress in orthopedic nanotechnology,ex-plores innovative applications of nanofibers in tendon repair,and evaluates the potential of selenium and cerium oxide nanoparticles in osteoarthritis and osteo-blast differentiation.This review also describes the emerging applications of inje-ctable hydrogels in cartilage engineering,emphasizing the critical role of inter-disciplinary research and highlighting the challenges and future prospects of in-tegrating nanotechnology into orthopedic clinical practice.This comprehensive approach provides a holistic perspective on the transformative impact of nanote-chnology in orthopedics,offering valuable insights for future research and clinical applications.

Injectable body temperature responsive hydrogel for encephalitis treatment via sustained release of nano-anti-inflammatory agents

Skull defects are common in the clinical practice of neurosurgery,and they are easily complicated by encephalitis,which seriously threatens the life and health safety of patients.The treatment of encephalitis is not only to save the patient but also to benefit the society.Based on the advantages of injectable hydrogels such as minimally invasive surgery,self-adaptation to irregularly shaped defects,and easy loading and delivery of nanomedicines,an injectable hydrogel that can be crosslinked in situ at the ambient temperature of the brain for the treatment of encephalitis caused by cranial defects is developed.The hydrogel is uniformly loaded with nanodrugs formed by cationic liposomes and small molecule drugs dexmedetomidine hydrochloride(DEX-HCl),which can directly act on the meninges to achieve sustained release delivery of anti-inflammatory nanodrug preparations and achieve the goal of long-term anti-inflammation at cranial defects.This is the first time that DEX-HCl has been applied within this therapeutic system,which is innovative.Furthermore,this study is expected to alleviate the long-term suffering of patients,improve the clinical medication strategies for anti-inflammatory treatment,promote the development of new materials for cranial defect repair,and expedite the translation of research outcomes into clinical practice.

Multimodal therapy strategies based on hydrogels for the repair of spinal cord injury

Spinal cord injury(SCI)is a serious traumatic disease of the central nervous system,which can give rise to the loss of motor and sensory function.Due to its complex pathological mechanism,the treatment of this disease still faces a huge challenge.Hydrogels with good biocompatibility and biodegradability can well imitate the extracellular matrix in the microenvironment of spinal cord.Hydrogels have been regarded as promising SCI repair material in recent years and continuous studies have confirmed that hydrogel-based therapy can effectively eliminate inflammation and promote spinal cord repair and regeneration to improve SCI.In this review,hydrogel-based multimodal therapeutic strategies to repair SCI are provided,and a combination of hydrogel scaffolds and other therapeutic modalities are discussed,with particular emphasis on the repair mechanism of SCI.

An injectable conductive hydrogel restores electrical transmission at myocardial infarct site to preserve cardiac function and enhance repair

Myocardial infarction(MI)leads to massive cardiomyocyte death and deposition of collagen fibers.This fibrous tissue disrupts electrical signaling in the myocardium,leading to cardiac systolic and diastolic dysfunction,as well as arrhythmias.Conductive hydrogels are a promising therapeutic strategy for MI.Here,we prepared a highly water-soluble conductive material(GP)by grafting polypyrrole(PPy)onto non-conductive gelatin.This component was added to the gel system formed by the Schiff base reaction between oxidized xanthan gum(OXG)and gelatin to construct an injectable conductive hydrogel.The prepared self-healing OGGP3(3 wt%GP)hydrogel had good biocompatibility,elastic modulus,and electrical conductivity that matched the natural heart.The prepared biomaterials were injected into the rat myocardial scar tissue 2 days after MI.We found that the cardiac function of the rats treated with OGGP3 was improved,making it more difficult to induce arrhythmias.The electrical resistivity of myocardial fibrous tissue was reduced,and the conduction velocity of myocardial tissue was increased.Histological analysis showed reduced infarct size,increased left ventricular wall thickness,increased vessel density,and decreased inflammatory response in the infarcted area.Our findings clearly demonstrate that the OGGP3 hydrogel attenuates ventricular remodeling and inhibits infarct dilation,thus showing its potential for the treatment of MI.

An injectable alginate/fibrin hydrogel encapsulated with cardiomyocytes and VEGF for myocardial infarction treatment

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.