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1.
Hydrogels have been applied to improve stem cell therapy and drug delivery, but current hydrogel‐based delivery methods are inefficient in clinical settings due to difficulty in handling and treatment processes, and low off‐the‐shelf availability. To overcome these limitations, an adhesive hyaluronic acid (HA) hydrogel patch is developed that acts as a ready‐to‐use tissue tape for therapeutic application. The HA hydrogel patches functionalized with phenolic moieties (e.g., catechol, pyrogallol) exhibit stronger tissue adhesiveness, greater elastic modulus, and increased off‐the‐shelf availability, compared with their bulk solution gel form. With this strategy, stem cells are efficiently engrafted onto beating ischemic hearts without injection, resulting in enhanced angiogenesis in ischemic regions and improving cardiac functions. HA hydrogel patches facilitate the in vivo engraftment of stem cell–derived organoids. The off‐the‐shelf availability of the hydrogel patch is also demonstrated as a drug‐loaded ready‐made tissue tape for topical drug delivery to promote wound healing. Importantly, the applicability of the cross‐linker‐free HA patch is validated for therapeutic cell and drug delivery. The study suggests that bioinspired phenolic adhesive hydrogel patches can provide an innovative method for simple but highly effective cell and drug delivery, increasing the off‐the‐shelf availability—a critically important component for translation to clinical settings.  相似文献   

2.
Antimicrobial therapy remains one of the major global challenges, particularly in the absence of effective treatment strategies for drug-resistant bacteria. In this study, a comprehensive treatment approach is proposed for drug-resistant bacterial wound infections based on the development of thermal-cascade multifunctional therapeutic systems (MTSs), spanning from the design of functional nanoscale materials to macroscopic smart hydrogel. Within the MTSs, functional antibiotic-loaded hybrid nanoclusters enable targeted therapeutic delivery and synergistic mild hyperthermia-antibiotic treatment, strongly suppressing drug-resistant bacteria while demonstrating excellent biocompatibility with normal cells and tissues. Furthermore, near-infrared irradiation can trigger the photothermal effects of hybrid nanoclusters to induce gelation of thermal-sensitive hydrogel, forming MTSs to serve as highly adaptable, drug-enriched protective dressings for infected wounds. Both in vitro and in vivo results substantiate that MTSs enhance the bioavailability of therapeutic agents (including bacterial internalization and tissue penetration), exert synergistic effects to completely eradicate drug-resistant bacteria, promoted wound healing and revascularization, and demonstrate excellent biocompatibility. This work offers an innovative demonstration to address drug-resistant bacterial infections through the advancement of sophisticated material systems.  相似文献   

3.
It is highly desirable yet significantly challenging to fabricate injectable, self-crosslinked, self-fused, and antifouling polyzwitterionic hydrogels, whose successful preparation will expand their application scope in biomedical fields. Herein, for the first time, a novel zwitterionic monomer, carboxybetaine urethane acrylate (CBUTA) is designed and synthesized with a urethane group and zwitterion on the same side chain. The strong inter-urethane H-bonds and zwitterionic dipole–dipole interactions of side chains contribute to self-crosslinked wholly supramolecular polyzwitterionic hydrogel that is directly formed from photoinitiated polymerization of CBUTA aqueous solution without adding any chemical crosslinkers. After being swollen in water, the polyCBUTA (PCBUTA) hydrogel is squeezed into small particles and freeze-dried to obtain hydrogel powder. The injectable and wholly zwitterionic supramolecular PCBUTA hydrogel can be easily reconstructed by mixing hydrogel powder with water due to the recombination of H-bonds of urethane groups and zwitterionic dipole–dipole interactions. The re-formed PCBUTA hydrogel exhibits an excellent self-fused and antifouling ability, and this injectable PCBUTA hydrogel, endowed with a microenvironment-regulated function, demonstrates excellent glucose consumption, antioxidation, antibacterial, and angiogenesis ability, thus accelerating the infected diabetic wound healing. Overall, this work provides a promising strategy to develop injectable and wholly zwitterionic hydrogels that will find broad biomedical applications.  相似文献   

4.
Diabetic foot ulcer (DFU) is one of the most common complications of diabetes, bringing physical and mental challenges for patients due to the lack of efficient curative therapy. Despite considerable advances in pharmacological and surgical approaches, clinical trials for DFU patients remain disappointing due to the local overactive and excessive inflammation. Immunomodulatory hydrogels has significant advantages to overcome the clinical challenge of DFUs therapy. Here, recent fabrication and regenerative advances in the utilization of functional hydrogels for altering the immune microenvironment of DFUs are comprehensively reviewed. The pathological features and the healing processes of DFUs, followed by summarizing the physicochemical properties essential for the design of regenerative hydrogels for immunomodulation in DFUs, are briefly introduced. Then, the potential immuno-therapeutic modalities of hydrogels and emerging trends used to treat DFUs via multitherapeutic approaches and enhanced efficacy and safety are discussed. Taken together, by linking the structural properties of hydrogels to their functions in DFU therapy with a particular focus on immunomodulatory stimuli, this review can promote further advances in designing advanced hydrogels for DFUs, resulting in improved diabetic wound repair through translation into clinical setting in the near future.  相似文献   

5.
Protein is the key composition of all tissues, which has also been widely used in tissue engineering due to its superior biocompatibility and low immunogenicity. However, natural protein usually lacks active functions such as vascularization, osteo‐induction, and neural differentiation, which limits its further applications as a functional biomaterial. Here, based on the mimetic extracellular matrix feature of bovine serum albumin, injectable polypeptide‐protein hydrogels with vascularization and antibacterial abilities are constructed successfully via coordinative cross‐linking of sulfydryl groups with silver ions (Ag+) for the regeneration of infected wound. In this protein hydrogel system, (Ag+), acting as crosslinkers, can not only provide a sterile microenvironment and a strong and robust antibacterial ability but also introduce K2(SL)6K2 (KK) polypeptide, which endows the hydrogel with vascularization behavior. Furthermore, the in vivo data show that the polypeptide‐protein hydrogel has a considerable collagen deposition and vascularization abilities in the early stage of wound healing, resulting in rapid new tissue regeneration featured with newly appeared hair follicles. Altogether, this newly developed multifunctional 3D polypeptide‐protein hydrogel with vascularization, antibacterial properties, and hair follicle promotion can be a promising approach in biomedical fields such as infected wound healing.  相似文献   

6.
Malignant bone tumors are often accompanied by osteolytic destruction and severe pathological fractures. Current therapeutic strategies can largely inhibit tumor proliferation, but the high recurrence rate of tumors and related bone defects remain a significant challenge. This study aims to address these issues by developing a novel near-infrared (NIR) light-responsive and a mechanically strong hydrogel that offers excellent photothermal tumor therapy and bone fracture repair capabilities. The as-prepared hydrogel exhibits good biocompatibility and an ultra-strong photothermal effect due to the formation of a complex network with up-conversion lanthanide-Au hybrid nanoparticles and alginate molecules. A subcutaneous tumor model is used to demonstrate that tumors can be efficiently eradicated via local photothermal treatment, where there is no tumor recurrence within the observation period. Moreover, the injected hydrogel becomes mechanically strong due to in situ Ca2+ crosslinking, which provides a supportive matrix to promote the repair of bone defects via stabilization of the fractured bone structure. The high photothermal effect and robust support offered by this single material demonstrate the potential of using the proposed hydrogel for the simultaneous treatment of bone tumor removal and bone healing.  相似文献   

7.
Easy cancer recurrence and wound infections have been clinical challenges after surgical treatment of melanoma. Herein, a silk-inspired in situ gelation system containing methacrylated silk fibroin (SF) and chlorine e6 for improved cancer therapy with enhanced wound healing is developed. Favored by the macrophage recruitment capacity of the SF hydrogel, promising antitumor immune responses can be turned “on” via near infrared irradiation in a controllable manner to achieve combination therapy with photodynamic therapy to significantly suppress melanoma recurrence. Moreover, the effective photodynamic antibacterial activity of this bioactive system with the capacity of light-controllable modulating macrophage phenotype promotes remarkable tissue ingrowth with hair follicle regeneration for Staphylococcus aureus infected wound healing. Thus, this multifunctional silk-based hydrogel system, as a desirable wound dressing, provides a new platform for promising melanoma therapy and skin regeneration.  相似文献   

8.
Persistent microbial infection and decreased neovascularization are common issues associated with diabetic wound treatment. Hydrogel dressings that offer intrinsic antibacterial and angiogenesis-inducing may substantially avoid the use of antibiotics or angiogenic agents. Herein, a versatile hydrogel is fabricated using an amyloid-derived toxin simulant (Fmoc-LFKFFK-NH2, FLN) as building blocks, inspired by the defense strategy of Staphylococcus aureus (S. aureus). The simulant assemblies of the hydrogel function as both matrix components and functional elements for diabetic wound treatment. The hydrogel undergoes quick assembly from random monomers to nanofibrils with abundant b-sheet driven by multiple non-covalent interactions. The developed hydrogel demonstrates excellent biocompatibility and accelerates angiogenesis via hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor A (VEGFA) signaling as a consequence of its amyloidal structure. The simulant-based nanofibrils endow the hydrogel with broad-spectrum antibacterial activity dominated by a membrane-disruption mechanism. In addition, the hydrogel exhibits excellent performance compared with the commercial hydrogel Prontosan in accelerating wound healing of diabetic mice infected with methicillin-resistant S. aureus (MRSA). This study highlights the fabrication of a single component and versatile hydrogel platform, thereby avoiding the drug-related side effects and complicated preparations and demonstrating its profound potential as a clinical dressing for the management of microbe-infected diabetic wounds.  相似文献   

9.
Shear‐thinning, self‐healing hydrogels are promising vehicles for therapeutic cargo delivery due to their ability to be injected using minimally invasive surgical procedures. An injectable hydrogel using a novel combination of dynamic covalent crosslinking with thermoresponsive engineered proteins is presented. Ex situ at room temperature, rapid gelation occurs through dynamic covalent hydrazone bonds by simply mixing two components: hydrazine‐modified elastin‐like protein (ELP) and aldehyde‐modified hyaluronic acid. This hydrogel provides significant mechanical protection to encapsulated human mesenchymal stem cells during syringe needle injection and rapidly recovers after injection to retain the cells homogeneously within a 3D environment. In situ, the ELP undergoes a thermal phase transition, as confirmed by coherent anti‐Stokes Raman scattering microscopy observation of dense ELP thermal aggregates. The formation of the secondary network reinforces the hydrogel and results in a tenfold slower erosion rate compared to a control hydrogel without secondary thermal crosslinking. This improved structural integrity enables cell culture for three weeks postinjection, and encapsulated cells maintain their ability to differentiate into multiple lineages, including chondrogenic, adipogenic, and osteogenic cell types. Together, these data demonstrate the promising potential of ELP–HA hydrogels for injectable stem cell transplantation and tissue regeneration.  相似文献   

10.
Full-thickness skin injuries have always been an intricate problem in clinical treatment. The application of biomaterials provides an artificial matrix for the recruitment of cells and deposition of extracellular matrix to accelerate wound healing. For the recovery of full-thickness skin defects, the double cross-linking of MgO-catechol and Schiff's base bonds are used as part of the gel-forming mechanism, and a bio-multifunctional hydrogel (CCOD-MgO) is prepared by adding MgO to catechol-modified chitosan (CHI-C) and oxidized dextran (ODex). The CCOD-MgO demonstrates high tissue adhesion, excellent self-repairing, hemostasis function, and low swelling rate. With the addition of MgO and catechol chelation, the adhesion strength of CCOD-MgO is about 35 kpa, which is much greater than fibrin glue. Moreover, the CCOD-MgO has better antibacterial properties than CHI-C/ODex hydrogel (CCOD) due to the synergy of chitosan and MgO in vitro. Accordingly, the CCOD-MgO can protect the wounds from infection and accelerate the healing speed of the epidermis in full-thickness cutaneous defect and burn model in vivo. These results demonstrate that the CCOD-MgO would be a promising therapeutic strategy in full-thickness skin injuries for clinical therapies.  相似文献   

11.
To elaborately construct a novel and efficient photothermal antibacterial nanoplatform is a promising strategy for treating bacterial wound infections. In this work, a composite hydrogel (CS/AM NSs hydrogel) with outstanding antibacterial ability is constructed by incorporating antimonene nanosheets (AM NSs) with extraordinary photothermal properties into the network structure of chitosan (CS). When cultured with bacteria, the CS/AM NSs hydrogel can gather bacteria on the surface through the interaction of CS with the bacterial cell membrane. Subsequently, the intrinsic bactericidal property of CS will kill some of the bacteria. After the introduction of near‐infrared laser, the AM NSs effectively convert light energy into localized heat to eliminate residual bacteria. By virtue of the synergistic action between the capture effect of CS and the photothermal effect of AM NSs, the CS/AM NSs hydrogel shows predominant antibacterial behavior against Escherichia coli and Staphylococcus aureus. In vitro assay and in vivo tests of infected full‐thickness defect wound healing confirm the satisfactory biocompatibility and antibacterial ability. Overall, this work reveals that the CS/AM NSs hydrogel holds great potential as a broad‐spectrum antibacterial wound dressing for treating bacteria‐infected wounds. Additionally, this is the first report of the application of AM NSs in the field of antibacterial treatment.  相似文献   

12.
Current treatments for chronic diabetic wounds remain unsatisfactory due to the lack of ideal wound dressings that can integrate matching mechanical strength, fast self-healability, facile dressing change, and multiple therapeutic effects into one system. In this work, benefiting from the catechol groups and therapeutic effect of epigallocatechin-3-gallate (EGCG, green tea derivative), a smart hydrogel dressing can be conveniently obtained through copolymerization of the complex formed by EGCG and 3-acrylamido phenylboronic acid (APBA) (the formation of boronate ester bond) and acrylamide. The resulting hydrogel features adequate mechanical properties, self-healing capability, and tissue adhesiveness. Otherwise, the substantial release of EGCG can not only realize anti-oxidation, antibacterial, anti-inflammatory and proangiogenic effect, and modulation of macrophage polarization to accelerate wound healing, but also facilitate easy dressing change. This advanced hydrogel provides a facile and effective way for diabetic chronic wound management and may be extended for the therapy of other complicated wound healings.  相似文献   

13.
Chronic refractory wounds have become a severe threat to public health and are characterized by repeated bacterial infections, persistent hypoxia, abnormal immune regulation, and obstruction of angiogenesis. However, current treatment strategies usually perform only one or two therapeutic functions and cannot satisfy the dynamic and complex demands of chronic wound healing. Herein, a versatile dynamic Schiff base and borate ester cross-linked glycopeptide hydrogel is prepared from phenylboronic acid-grafted ε-polylysine (EPBA), epigallocatechin-3-gallate (EGCG), and oxidized alginate. Customized polydopamine-coated honeycomb MnO2 nanoparticles loaded with herb-derived salvianolic acid B (PHMS) are embedded into the hydrogel before gelation. Under the distinct acidic and oxidative microenvironment of chronic refractory wounds, the hydrogel gradually dissociates, and the released EPBA effectively eliminates bacteria, while the released EGCG and PHMS eradicates reactive oxygen and nitrogen species, promotes M2 polarization of macrophages, and continuously generates oxygen. Then PHMS further disintegrates, and the released salvianolic acid B promotes angiogenesis through the PI3K/Akt pathway. The versatile glycopeptide hydrogel accelerates Staphylococcus aureus-infected diabetic cutaneous wound repair in vivo and is a promising candidate dressing for chronic refractory wound healing.  相似文献   

14.
Chronic wounds do not heal in an orderly fashion in part due to the lack of timely release of biological factors essential for healing. Topical administration of various therapeutic factors at different stages is shown to enhance the healing rate of chronic wounds. Developing a wound dressing that can deliver biomolecules with a predetermined spatial and temporal pattern would be beneficial for effective treatment of chronic wounds. Here, an actively controlled wound dressing is fabricated using composite fibers with a core electrical heater covered by a layer of hydrogel containing thermoresponsive drug carriers. The fibers are loaded with different drugs and biological factors and are then assembled using textile processes to create a flexible and wearable wound dressing. These fibers can be individually addressed to enable on‐demand release of different drugs with a controlled temporal profile. Here, the effectiveness of the engineered dressing for on‐demand release of antibiotics and vascular endothelial growth factor (VEGF) is demonstrated for eliminating bacterial infection and inducing angiogenesis in vitro. The effectiveness of the VEGF release on improving healing rate is also demonstrated in a murine model of diabetic wounds.  相似文献   

15.
The widespread multidrug resistance resulting from the abuse of antibiotics motivates researchers to explore alternative methods to treat bacterial infections. Recently, the emergence of nanozymes has provided a potential approach to combat bacteria. Such nanozymes can mimic the functions of natural enzymes to induce the production of highly toxic reactive oxygen species (ROS) as an antibacterial. However, the lack of effective interaction between nanozymes and bacteria, and the intrinsic short lifetime and diffusion distance of ROS greatly compromise their bactericidal activity. Furthermore, the dead bacteria left in the infected area can give rise to unexpected tissue inflammation. Herein, for the first time, a nanozyme‐hydrogel is constructed to realize reinforced antibacterials. The nanozyme‐hydrogel with the traits of positive charge and macropore can capture and restrict bacteria in the range of ROS destruction. Significantly, by combining the near‐infrared photothermal property of nanozymes, the nanozyme‐hydrogel can achieve a synergistic bactericidal effect. More importantly, the nanozyme‐hydrogel can eliminate bacteria and reduce the risk of inflammation. In consequence, the current work manifests an original strategy to improve the antibacterial performance of nanozymes, concurrently promote wound healing.  相似文献   

16.
Chronic hyperglycemic damage is a major problem that undermines diabetic wound healing. By combining treatment and diagnosis together, blood glucose concentration can be monitored real-time through medical imaging devices and precise interventions can be carried out at the right time to promote diabetic wound repair. In this study, an injectable self-healing hyaluronic acid hydrogel is constructed using Schiff base reaction, and nanoenzymes (GOx-MnO2) synthesized by condensation reaction, along with vascular endothelial growth factor (VEGF)-nanobubbles produced by double emulsification method, are loaded into the hydrogel, thus constructing an innovative diagnostic and therapeutic hydrogel system (US@GOx@VEGF hydrogel, UGV hydrogel). While monitoring glucose concentration in real-time, the system delivers VEGF through ultrasound in a precise and noninvasive way to deplete glucose. The UGV hydrogel integrates both processes of diagnosis and treatment, effectively releases VEGF through blasts triggered by ultrasound. Apart from this, this new trauma patch is capable of monitoring Mn2+ values ranging from 0.5 m to 7.8 × 10−3 m and glucose levels from 100 × 10−3 to 3 × 10−3 m , through magnetic resonance imaging. In summary, the hydrogel realizes real-time monitoring of glucose level, maintains glucose homeostasis through noninvasive intervention, and rapidly promotes the repair of diabetic skin defects, opening up a new path for chronic wound management.  相似文献   

17.
A novel biocompatible polysaccharide‐based self‐healing hydrogel, CEC‐l‐OSA‐l‐ADH hydrogel (“l” means “linked‐by”), is developed by exploiting the dynamic reaction of N‐carboxyethyl chitosan (CEC) and adipic acid dihydrazide (ADH) with oxidized sodium alginate (OSA). The self‐healing ability, as demonstrated by rheological recovery, macroscopic observation, and beam‐shaped strain compression measurement, is attributed to the coexistence of dynamic imine and acylhydrazone bonds in the hydrogel networks. The CEC‐l‐OSA‐l‐ADH hydrogel shows excellent self‐healing ability under physiological conditions with a high healing efficiency (up to 95%) without need for any external stimuli. In addition, the CEC‐l‐OSA‐l‐ADH hydrogel exhibits good cytocompatibility and cell release as demonstrated by three‐dimensional cell encapsulation. With these superior properties, the developed hydrogel holds great potential for applications in various biomedical fields, e.g., as cell or drug delivery carriers.  相似文献   

18.
Bacterial infections are one of the biggest threats to wound healing. Despite significant efforts in wound condition monitoring and treatment, significant challenges remain in real-time wound monitoring and timely treatment. Herein, a kind of hydrogel with dual functions, which can not only quickly diagnose wound bacterial infection but also provide timely and effective treatment is developed. First, Carborxymethy chitosan (CMCS)-Protocatechualdehyde (PA)@Fe hydrogels with double dynamic bonds are prepared by chelating PA@Fe with CMCS. Second, the pH-sensitive Polydimethylsiloxane (PDMS) optical fibers are integrated into the CMCS-PA@Fe hydrogels to obtain the pH-sensitive optical fiber/CMCS-PA@Fe hydrogels that exhibit good real-time monitoring of the wound healing process. The tissue adhesion and self-healing properties of the pH-sensitive optical fiber/CMCS-PA@Fe hydrogels can adapt to the movement and stretching of the skin. Meanwhile, with the assistance of the photothermal effect, the hydrogels have a high antibacterial effect (>99.9%). In addition, the pH-sensitive optical fiber/CMCS-PA@Fe hydrogels also show an excellent therapeutic effect in the wound infection model. Moreover, reliable and timely wound pH information can be sent to intelligent devices through microcomputers to monitor the healing status. Overall, the pH-sensitive optical fiber/CMCS-PA@Fe hydrogels provide an entirely new platform for developing smart, real-time diagnostics and timely wound treatment.  相似文献   

19.
The surgical procedure in skin‐tumor therapy usually results in cutaneous defects, and multidrug‐resistant bacterial infection could cause chronic wounds. Here, for the first time, an injectable self‐healing antibacterial bioactive polypeptide‐based hybrid nanosystem is developed for treating multidrug resistant infection, skin‐tumor therapy, and wound healing. The multifunctional hydrogel is successfully prepared through incorporating monodispersed polydopamine functionalized bioactive glass nanoparticles (BGN@PDA) into an antibacterial F127‐ε‐Poly‐L‐lysine hydrogel. The nanocomposites hydrogel displays excellent self‐healing and injectable ability, as well as robust antibacterial activity, especially against multidrug‐resistant bacteria in vitro and in vivo. The nanocomposites hydrogel also demonstrates outstanding photothermal performance with (near‐infrared laser irradiation) NIR irradiation, which could effectively kill the tumor cell (>90%) and inhibit tumor growth (inhibition rate up to 94%) in a subcutaneous skin‐tumor model. In addition, the nanocomposites hydrogel effectively accelerates wound healing in vivo. These results suggest that the BGN‐based nanocomposite hydrogel is a promising candidate for skin‐tumor therapy, wound healing, and anti‐infection. This work may offer a facile strategy to prepare multifunctional bioactive hydrogels for simultaneous tumor therapy, tissue regeneration, and anti‐infection.  相似文献   

20.
Antibacterial hydrogel has received extensive attention in soft tissue repair, especially preventing infections those associated with impaired wound healing. However, it is challenging in developing an inherent antibacterial hydrogel integrating with excellent cell affinity and superior mechanical properties. Inspired by the mussel adhesion chemistry, a contact‐active antibacterial hydrogel is proposed by copolymerization of methacrylamide dopamine (MADA) and 2‐(dimethylamino)ethyl methacrylate and forming an interpenetrated network with quaternized chitosan. The reactive catechol groups of MADA endow the hydrogel with contact intensified bactericidal activity, because it increases the exposure of bacterial cells to the positively charged groups of the hydrogel and strengthens the bactericidal effect. MADA also maintains the good adhesion of fibroblasts to the hydrogel. Moreover, the hybrid chemical and physical cross‐links inner the hydrogel network makes the hydrogel strong and tough with good recoverability. In vitro and in vivo tests demonstrate that this tough and contact‐active antibacterial hydrogel is a promising material to fulfill the dual functions of promoting tissue regeneration and preventing bacterial infection for wound‐healing applications.  相似文献   

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