Hydrogel Degradation Research Articles

Dental Pulp Stem Cell Lysate-Based Hydrogel Improves Diabetic Wound Healing via the Regulation of Anti-Inflammatory Macrophages and Keratinocytes.

The prolonged existence of chronic wounds heightens the risk of patients experiencing chronic pain, necrosis, and amputation. Dental pulp stem cells (DPSCs) have garnered attention due to their potential immunomodulatory and tissue repair regenerative effects in the management of chronic wounds. However, stem-cell-based therapy faces challenges such as malignant differentiation, immune rejection, and long-term effectiveness. To overcome these challenges, we proposed a chronic wound therapy using a hydrogel derived from human-originated dental pulp stem cell lysate (DPSCL). Our data indicate that, with the degradation of the dental pulp stem cell lysate-based hydrogel (DPSCLH), the slowly released cell lysates recruit anti-inflammatory M2 macrophages and promote the proliferation, migration, and keratinization of HacaT cells. In addition, in vivo studies revealed that DPSCLH avoids immune rejection reactions and induces a long-term accumulation of endogenous M2 macrophages. In a mouse model of diabetic wounds, DPSCLH effectively modulates the inflammatory microenvironment around diabetic wounds, promotes the formation of the stratum corneum, and facilitates the healing of wounds, thus holding tremendous potential for the treatment of diabetic wounds.

Intervening to Preserve Function in Ischemic Cardiomyopathy with a Porous Hydrogel and Extracellular Matrix Composite in a Rat Myocardial Infarction Model.

Multiple hydrogels are developed for injection therapy after myocardial infarction, with some incorporating substances promoting tissue regeneration and others emphasizing mechanical effects. In this study, porosity and extracellular matrix-derived digest (ECM) are incorporated, into a mechanically optimized, thermoresponsive, degradable hydrogel (poly(N-isopropylacrylamide-co-N-vinylpyrrolidone-co-MAPLA)) and evaluate whether this biomaterial injectate can abrogate adverse remodeling in rat ischemic cardiomyopathy. After myocardial infarction, rats are divided into four groups: NP (non-porous hydrogel) without either ECM or porosity, PM (porous hydrogel) from the same synthetic copolymer with mannitol beads as porogens, and PME with porosity and ECM digest added to the synthetic copolymer. PBS injection alone is a control group. Intramyocardial injections occurred 3 days after myocardial infarction followed by serial echocardiography and histological assessments 8 weeks after infarction. Echocardiographic function and neovascularization improved in the PME group compared to the other hydrogels and PBS injection. The PME group also demonstrated improved LV geometry and macrophage polarization (toward M2) compared to PBS, whereas differences are not observed in the NP or PM groups versus control. These results demonstrate further functional improvement may be achieved in hydrogel injection therapy for ischemic cardiomyopathy by incorporating porosity and ECM digest, representing combined mechanical and biological effects.

Sodium alginate hydrogels co-encapsulated with cell free fat extract-loaded core-shell nanofibers and menstrual blood stem cells derived exosomes for acceleration of articular cartilage regeneration

This study presents a novel scaffold system comprising sodium alginate hydrogels (SAh) co-encapsulated with cell-free fat extract (CEFFE)-loaded core-shell nanofibers (NFs) and menstrual blood stem cell-derived exosomes (EXOs). The scaffold integrates the regenerative potential of EXOs and CFFFE, offering a multifaceted strategy for promoting articular cartilage repair. Coaxially electrospun core-shell NFs exhibited successful encapsulation of CEFFE and seamless integration into the SAh matrix. Structural modifications induced by the incorporation of CEFFE-NFs enhanced hydrogel porosity, mechanical strength, and degradation kinetics, facilitating cell adhesion, proliferation, and tissue ingrowth. The release kinetics of growth factors from the composite scaffold demonstrated sustained and controlled release profiles, essential for optimal tissue regeneration. In vitro studies revealed high cell viability, enhanced chondrocyte proliferation, and migration in the presence of EXOs/CEFFE-NFs@SAh composite scaffolds. Additionally, in vivo experiments demonstrated significant cartilage regeneration, with the composite scaffold outperforming controls in promoting hyaline cartilage formation and defect bridging. Overall, this study underscores the potential of EXOs and CEFFE-NFs integrated into SAh matrices for enhancing chondrocyte viability, proliferation, migration, and ultimately, articular cartilage regeneration. Future research directions may focus on elucidating underlying mechanisms and conducting long-term in vivo studies to validate clinical applicability and scalability.

Drug conjugates crosslinked bioresponsive hydrogel for combination therapy of diabetic wound

Basic fibroblast growth factor (bFGF) has proved to be effective for wound healing, yet its effectiveness is extremely retarded in diabetic wounds due to the severe oxidative stress in wound beds. To solve this issue, herein a novel combination therapy of bFGF and N-acetylcysteine (NAC, antioxidant) was devised for improved diabetic wound repair. To avoid rapid loss of both drugs in the wound beds, a bioresponsive hydrogel (bFGF-HSPP-NAC) was engineered by incorporating bFGF and NAC into polymer-drug conjugates (HSPP) via thiol-disulfide exchange reactions. In response to oxidative stress (e.g., reactive oxygen species), the disulfide bonds (SS) within the hydrogel are broken into thiol groups (-S-H), thereby promoting hydrogel degradation and enabling controlled drug release. Initially, NAC is released to scavenge free radicals and ameliorate oxidative damage. Subsequently, bFGF is released to expedite tissue regeneration. This combinatorial strategy is tailored to the specific characteristics of the wound microenvironment at various stages of diabetic wound healing, thereby achieving therapeutic efficacy. The results indicate that the bFGF-HSPP-NAC hydrogel markedly enhances re-epithelialization, collagen deposition, hair follicle regeneration, and neovascularization. In conclusion, the bioresponsive bFGF-HSPP-NAC hydrogel demonstrates significant potential for application in combinatorial therapeutic approaches for diabetic wound healing.

3D Nanofiber-Assisted Embedded Extrusion Bioprinting for Oriented Cardiac Tissue Fabrication.

Three-dimensional (3D) bioprinting technology stands out as a promising tissue manufacturing process to control the geometry precisely with cell-loaded bioinks. However, the isotropic culture environment within the bioink and the lack of topographical cues impede the formation of oriented cardiac tissue. To overcome this limitation, we present a novel method named 3D nanofiber-assisted embedded bioprinting (3D-NFEP) to fabricate cardiac tissue with an oriented morphology. Aligned 3D nanofiber scaffolds were fabricated by divergence electrospinning, which provided structural support for printing of the low-viscosity bioink and structural induction to cardiomyocytes. Cells adhered to the aligned fibers after hydrogel degradation, and a high degree of cell alignment was observed. This technology was also demonstrated as a feasible solution for multilayer cell printing. Therefore, 3D-NFEP was demonstrated as a promising method for bioprinting oriented cardiac tissue with low-viscosity bioink and is expected to be applied for structured and cardiac tissue engineering.

A Thermosensitive and Degradable Chitin-Based Hydrogel as a Brucellosis Vaccine Adjuvant.

Brucellosis is a zoonotic infectious disease that has long endangered the development of animal husbandry and human health. Currently, vaccination stands as the most efficacious method for preventing and managing brucellosis. Alum, as the most commonly used adjuvant for the brucellosis vaccine, has obvious disadvantages, such as the formation of granulomas and its non-degradability. Therefore, the aims of this study were to prepare an absorbable, injectable, and biocompatible hydroxypropyl chitin (HPCT) thermosensitive hydrogel and to evaluate its immunization efficacy as an adjuvant for Brucella antigens. Specifically, etherification modification of marine natural polysaccharide chitin was carried out to obtain a hydroxypropyl chitin. Rheological studies demonstrated the reversible temperature sensitivity of HPCT hydrogel. Notably, 5 mg/mL of bovine serum albumin can be loaded in HPCT hydrogels and released continuously for more than one week. Furthermore, the L929 cytotoxicity test and in vivo degradation test in rats proved that an HPCT hydrogel had good cytocompatibility and histocompatibility and can be degraded and absorbed in vivo. In mouse functional experiments, as adjuvants for Brucella antigens, an HPCT hydrogel showed better specific antibody expression levels and cytokine (Interleukin-4, Interferon-γ) expression levels than alum. Thus, we believe that HPCT hydrogels hold much promise in the development of adjuvants.

Tough gelatine hydrogels reinforced with silk fibroin nanofiber

Gelatine hydrogels exhibit potential as biomaterials such as wound-healing materials, artificial organs, scaffolds for cell culture and drug delivery systems because of their good biocompatibility. However, their practical applications are limited by their poor mechanical properties and high degradability. In this study, mechanically fibrillated silk fibroin (fibroin nanofibers; FNF) was used to reinforce gelatine hydrogels. The resulting gelatine hydrogels with FNF exhibited enhanced toughness compared to those reinforced with conventional aqueous regenerated fibroin (RF), which were prepared by treatment with a highly concentrated LiBr solvent or a neat gelatine hydrogel while retaining their softness. The average pore size of the gelatine hydrogel was 2.2 μm, while the gelatine hydrogel containing 25 % FNF expanded to 6.7 μm. A web-like network was formed between the pores. The addition of FNF increased the relative β-sheet contents in the hydrogels to 60.3 %, suggesting that this may have caused structural changes such as increased crystallinity for gelatine-derived proteins. Furthermore, the addition of FNF inhibited the rapid enzymatic degradation of gelatine hydrogels. FNF, which can be easily prepared in water, is a safe material for both the environment and living organisms and holds promise as a biomaterial in the future.

Wireless matrix metalloproteinase-9 sensing by smart wound dressing with controlled antibacterial nanoparticles release toward chronic wound management

Chronic wounds cause serious health and economic burdens on patients and society. Herein, a wireless and flexible smart wound dressing was developed for matrix metalloproteinase-9 (MMP-9) monitoring and antimicrobial treatment toward chronic wound management. The highly sensitive radio frequency MMP-9 sensor was realized based on a bioresponsive hydrogel with bioactive sequences of the arginyl-glycyl-aspartic acid peptide. Taking advantage of the flexible inductive-capacitive (LC) circuit and bioresponsive hydrogel, the wireless and wearable smart wound dressing offered an efficient strategy for in-situ wound analysis. Besides, the controlled release of silver nanoparticles (AgNPs) from the degradable hydrogel exhibited significant antimicrobial efficacy against typical bacteria in wound infection including Escherichia coli and Staphylococcus aureus. The analysis of MMP-9 in wound exudate from diabetic foot ulcer (DFU) patients demonstrated good accuracy cross-validated with gold-standard fluorescent measurements, providing great potential for personalized wound management.

Engineering and Monitoring the Sustained Release of Extracellular Vesicles from Hydrogels for In Vivo Therapeutic Applications

Extracellular vesicles (EVs) are gaining interest in regenerative medicine and biomaterials have been shown to extend EV bioavailability following delivery. Herein, the labeling of both hydrogels and EVs is reported to better understand hydrogel design for sustained EV release into tissues. Shear‐thinning hydrogels are engineered using guest–host (i.e., adamantane–cyclodextrin) modifications to hyaluronic acid (GH), as well as GH hydrogels with the addition of gelatin crosslinked via transglutaminase (GH+Gel) to temporally control hydrogel properties. When labeled with a near‐IR dye and injected into rat myocardial tissue, the GH+Gel hydrogel is retained (>14 days) longer than the GH hydrogel alone (≈7 days), likely due to the added gelatin network. To overcome challenges associated with common EV labeling methods, a highly versatile metabolic labeling methodology is utilized via the incorporation of N‐azidoacetylmannosamine‐tetraacylated during EV synthesis to introduce azide groups that can then be reacted with DBCO dyes. When injected in saline, EVs are cleared within 24 h in hearts; however, hydrogels enhance EV retention, with levels based on hydrogel degradation behavior, namely, >14 days for GH+Gel hydrogel and ≈7 days for GH hydrogel alone. These findings support the use of hydrogels in EV therapies.

Tailoring pH-sensitive carboxymethyl tamarind kernel gum-based hydrogel for an efficient delivery of hydrophobic drug indomethacin

Polyacrylamide hydrogels have gained attention in the drug delivery field for their pH-dependent nature. Nevertheless, their limited degradability and lower entrapment efficiency for hydrophobic drugs hinder their utility in controlled drug release. This research aims to design a degradable pH-sensitive hydrogel for delivering the hydrophobic drug indomethacin to the colon. This work developed and optimized the hydrogels based on β-cyclodextrin, carboxymethyl tamarind kernel gum, and polyacrylamide with varying amounts of polyethylene glycol diacrylate. The optimized hydrogel exhibits 76.52 % gel fraction, 89.21 % porosity, 1000.27 % swelling, and 90.0 % equilibrium water content. The hydrogel was characterized using Attenuated Total Reflection-Fourier Transform Infrared spectroscopy, confirming the successful crosslinking of the synthesized hydrogel. Powder X-ray Diffraction revealed their amorphous nature while Scanning Electron Microscopy showed a porous surface morphology of the hydrogel. Moreover, rheology confirmed the hydrogel's elastic nature. Notably, the hydrogel demonstrated a drug release of 60.26 % at pH 7.4. Kinetic modelling of indomethacin release data indicated a Fickian diffusion release mechanism. Cytotoxicity tests on HCT-116 cells showed 79 % viability, and the hydrogel fully degraded within 10 days. These results confirmed the potential of synthesized β-CD/PAM/CMTKG hydrogel for controlled indomethacin delivery to the colon.

3D printed degradable hydrogel evaporator for high-efficiency, environmental-friendly solar alkaline-water evaporation

Solar evaporation is a simple, cost-effective method for producing clean water that does not require complex infrastructure and fossil energy. Although there have been significant advances in hydrogel solar evaporators, their widespread applications are still hampered by challenges related to customizing the structures to optimize solar evaporation rates and managing the pollution associated with waste hydrogel evaporators. To address these issues, we construct a customizable in structure, highly efficient and degradable interfacial solar evaporator using three-dimensional (3D) printing technique. The complex 3D microstructures can significantly enhance sunlight absorption through multiple surface reflections and anti-reflection effects, which can achieve customized evaporation performance. The optimized tree-shaped hydrogel evaporators can achieve a high evaporation rate of 2.41 kg m–2 h−1 under 1 sun. Importantly, the hydrogel evaporators exhibit degradation properties in alkaline liquids. These components can be integrated into the environment, reducing their impact on the environment and achieving sustainable utilization, offering a promising solution for alkaline wastewater purification and demonstrating the potential of environmental-friendly solar evaporator technology.

Thermosensitive Hydrogel with Programmable, Self‐Regulated HIF‐1α Stabilizer Release for Myocardial Infarction Treatment

AbstractHIF‐1α (hypoxia induced factor‐1α), a vital protective signal against hypoxia, has a short lifetime after myocardial infarction (MI). Increasing HIF‐1α stability by inhibiting its hydroxylation with prolyl hydroxylases inhibitors such as DPCA (1,4‐dihydrophenonthrolin‐4‐one‐3‐carboxylic acid) presents positive results. However, the optimal inhibitor administration profile for MI treatment is still unexplored. Here, injectable, thermosensitive hydrogels with programmable DPCA release are designed and synthesized. Hydrogel degradation and slow DPCA release are coupled to form a feedback loop by attaching pendant DPCA to polymer backbone, which serve as additional crosslinking points through π–π and hydrophobic interactions. Pendant carboxyl groups are added to the copolymer to accelerate DPCA release. Burst release in the acute phase for myocardial protection and extended near zero‐order release across the inflammatory and fibrotic phases with different rates are achieved. All DPCA‐releasing hydrogels upregulate HIF‐1α, decrease apoptosis, promote angiogenesis, and stimulate cardiomyocyte proliferation, leading to preserved cardiac function and ventricular geometry. Faster hydrogel degradation induced by faster DPCA release results in a HIF‐1α expression eight times of healthy control and better therapeutic effect in MI treatment. This research demonstrates the value of precise regulation of HIF‐1α expression in treating MI and other relevant diseases and provides an implantable device‐based modulation strategy.

Internally-crosslinked alginate dialdehyde/alginate/gelatin-based hydrogels as bioprinting inks for prospective cardiac tissue engineering applications

Cardiovascular diseases represent a worldwide social and economic challenge, due to heart tissue limited regenerative capabilities. 3D bioprinted cell-laden constructs are a promising approach to develop patches for cardiac regeneration or in vitro models for new drug preclinical discovery and validation. However, the development of bioinks with optimal mechanical, rheological, and biological properties is still a challenge. Although alginate (Alg)-based bioinks have been extensively explored, such hydrogels lack cell adhesion properties and degradability. Additionally, 3D Alg structures are usually obtained by micro-extrusion bioprinting exploiting conventional external cross-linking methods, which introduce inhomogeneities and unpredictability in construct formation. This work exploits Alg internal ionic gelation mechanism to obtain homogeneous self-standing multilayered 3D printed constructs without employing support baths or post-printing crosslinking treatments, combining an insoluble calcium salt (calcium carbonate, CaCO3) with an acidifying agent (D-(+)-Glucono-1,5-lactone, GDL) to promote controlled release of calcium ions. Alg was blended with oxidized alginate (ADA) and gelatin (Gel) to achieve degradable and cell adhesive hydrogels for cardiac tissue engineering. Firstly, ADA/Alg bioink composition was tailored by varying polymer weight ratio (keeping ADA as the main component) and calcium ions concentration to achieve cardiac tissue-like viscoelastic properties. Then, the amount of Gel in ADA/Alg hydrogels was optimized to support adult human cardiac fibroblasts (AHCFs) adhesion, producing shear thinning inks with tunable viscoelastic properties (G’ 650-1300 Pa) and degradation profile (40-80% weight loss after 21 days in phosphate buffered saline, PBS) by varying Gel concentration. ADA/Alg/Gel hydrogels showed a shear thinning behavior suitable for 3D bioprinting and dependent on ink stabilization time, due to the gradual pH-triggered release of calcium ions over time. AHCFs-laden ADA/Alg/Gel bioinks could be successfully printed producing scaffolds with high shape fidelity and good cell viability post-printing. Finally, 3D AHCF-laden and H9C2-laden ADA/Alg/Gel bioinks with the highest gelatin content (25% w/w) allowed cell adhesion after 24 hours of incubation, showing potential application for cardiac tissue modelling. This research presented a comprehensive framework for advancing the design of bioink formulations enabling the printing of cell-adhesive and self-supporting constructs.

Biodegradable Natural Hydrogels for Tissue Engineering, Controlled Release, and Soil Remediation.

This article provides insights into hydrogels of the most promising biodegradable natural polymers and their mechanisms of degradation, highlighting the different possibilities of controlling hydrogel degradation rates. Since biodegradable hydrogels can be designed as scaffolding materials to mimic the physical and biochemical properties of natural tissues, these hydrogels have found widespread application in the field of tissue engineering and controlled release. In the same manner, their potential as water reservoirs, macro- and microelement carriers, or matrixes for the selective adsorption of pollutants make them excellent candidates for sustainable soil amendment solutions. Accordingly, this article summarizes the recent advances in natural biodegradable hydrogels in the fields of tissue engineering, controlled release, and soil remediation, emphasizing the new opportunities that degradability and its tunability offer for the design and applicability of hydrogels.

Ultrasound-Responsive HBD Peptide Hydrogel with Antibiofilm Capability for Fast Diabetic Wound Healing.

Despite advancements in therapeutic agents for diabetic chronic wounds, challenges such as suboptimal bioavailability, intricate disease milieus, and inadequate delivery efficacy have impeded treatment outcomes. Here, ultrasound-responsive hydrogel incorporated with heparin-binding domain (HBD) peptide nanoparticles is developed to promote diabetic wound healing. HBD peptide, derived from von Willebrand Factor with angiogenic activity, are first engineered to self-assemble into nanoparticles with enhanced biostability and bioavailability. Ultrasound responsive cargo release and hydrogel collapses are first verified through breakage of crosslinking. In addition, desired antioxidant and antibacterial activity of such hydrogel is observed. Moreover, the degradation of hydrogel under ultrasound stimulation into smaller fragments facilitated the deeper wound penetration of ≈400 µm depth. Complete wound closure is observed from diabetic mice with chronic wounds after being treated with the proposed hydrogel. In detail, in vivo studies revealed that hydrogels loaded with HBD peptide nanoparticles increased the levels of angiogenesis-related growth factors (VEGF-A, CD31, and α-SMA) to effectively accelerate wound repair. Overall, this study demonstrates that ultrasound-responsive HBD peptide hydrogel provides a synergistic therapeutic strategy for external biofilm elimination and internal effective delivery for diabetic wounds with biofilm infection.

Effect of oxidized Bletilla striata polysaccharide on fibrin hydrogel formation and its application in wound healing dressing

Wound healing is influenced by various factors, including oxidative damage, bacterial infection, and inadequate angiogenesis, which collectively contribute to a protracted healing process. In this work, we designed innovative multifunctional hydrogels based on fibrin integrated with Bletilla striata polysaccharides (BSP) or oxidated Bletilla striata polysaccharides (OBSP) for use as wound dressings. The preliminary structure and bioactivity of BSP and OBSP were investigated. The effect of polysaccharides on the self-assembly process of fibrin hydrogels were also evaluated. BSP and OBSP significantly altered the initial fibrin fibrillogenesis and the ultimate structure of the fibrin network. Relative to pure fibrin hydrogel, the incorporation of BSP and OBSP enhanced water swelling and retention, and decelerated the degradation of hydrogels in PBS. Furthermore, BSP and OBSP augmented the antioxidant, antibacterial, and anti-inflammatory properties of fibrin hydrogels, with OBSP demonstrating superior performance in these aspects. Through the development of a murine wound model, it was observed that the wound healing efficacy of hydrogels incorporating BSP and OBSP surpassed that of the pure fibrin group. Notably, the hydrogel formulated with 25 mg/mL OBSP exhibited the most pronounced therapeutic effect, achieving a healing rate approaching 100 %. Consequently, fibrin-OBSP composite hydrogels demonstrate significant potential as wound dressings.

Fungal Enzyme-Responsive Hydrogel Drug Delivery Platform for Triggered Antifungal Release.

Fungal infections can lead to debilitating consequences if they are not treated effectively. Antifungal drugs used to treat these infections can be toxic and overuse contributes to growing antifungal resistance. Candida spp., particularly C. albicans, are implicated in a majority of these infections. Virulent C. albicans produce secreted aspartic proteases (Saps) that aid in pathogen tissue invasion and proliferation at an infected site. Here, fungi-responsive hydrogels are developed that degrade in the presence of Saps to provide a triggered release of encapsulated liposomal antifungals. The hydrogel backbone incorporates a Sap-cleavable peptide sequence enabling Sap-responsive degradation. Hydrogels are found to effectively degrade in the presence of Saps extracted from C. albicans. Encapsulated liposomal antifungals show similar release kinetics as hydrogel degradation products in the presence of Saps, supporting a degradation-dependent release mechanism. Antifungal liposome-loaded responsive hydrogels exhibit successful eradication of C. albicans cultures and remain stable in sterile murine wound fluid. Finally, no significant cytotoxicity is observed for murine fibroblast cells and red blood cells exposed to hydrogel degradation products. These fungi-responsive hydrogels have the potential to be used for local, on-demand delivery of antifungal drugs, for effective treatment of fungal infections while helping to limit unnecessary exposure to thesetherapeutics.

Highly Sensitive, Degradable, and Rapid Self-Healing Hydrogel Sensor with Semi-Interpenetrating Network for Recognition of Micro-Expressions.

Flexible conductive hydrogels have revolutionized the lives and are widely applied in health monitoring and wearable electronics as a new generation of sensing materials. However, the inherent low mechanical strength, sensitivity, and lack of rapid self-healing capacity results in their short life, poor detection accuracy, and environmental pollution. Inspired by the molecular structure of bone and its chemical characteristics, a novel fully physically cross-linked conductive hydrogel is fabricated by the introduction of nanohydroxyapatite (HAp) as the dynamic junction points. In detail, the dynamically cross-linked network, including multiple physical interactions, provides it with rapid self-healing ability and excellent mechanical properties (elongation at break (>1200%), tensile strength (174kPa), and resilience (92.61%)). Besides, the ions (Cl-, Li+, Ca2+) that move freely within the system impart outstanding electrical conductivity (2.46±0.15 S m-1), high sensitivity (gauge factor, GF>8), good antifreeze (-40.2°C), and humidity properties. The assembled sensor can be employed to sensitively detect various large human motions and subtle changes in behavior (facial expressions, speech recognition). Meanwhile, the hydrogel sensor can also degrade in phosphate-buffered saline solution without causing any environmental pollution. Therefore, the designed hydrogels may become a promising candidate material in the future potential applications for smart wearable sensors and electronic skin.

Photo-crosslinking methacrylated-amylopectin/polyacrylamide hydrogels loading curcumin for applications as degradable, injectable, and antibacterial wound dressings

The preparation of biodegradable and antibacterial hydrogels has important clinical value. In this work, a novel strategy has been developed to prepare degradable hydrogel dressings without chemical crosslinking agent using methacrylate anhydride (MA)-modified amylopectin (APMA) and polyacrylamide (PAM). After introducing CC bonds, APMA/PAM hydrogels can be formed under light irradiation. This strategy improves the gelling ability of AP and degradation properties of the hydrogel by avoiding the addition of crosslinking agent. The degradation rate of APMA/PAM hydrogel is 74.04 ± 0.69 % within 12 weeks, while that of APMA/PAM hydrogel containing crosslinking agent is only 38.5 ± 0.1 %. The APMA/PAM hydrogel loading curcumin (Cur) (APMA/PAM-Cur) exhibits high antibacterial efficiency of 98.29 ± 0.41 % and 97.18 ± 0.81 % against S. aureus and E. coli, respectively, with light irradiation. Animal experiments show that the APMA/PAM-Cur hydrogel reduces the infiltration of inflammatory factors, increases the density of collagen, and makes the newly formed granulation tissue thicker and tighter. This study not only proves the promising potential of the APMA/PAM-Cur hydrogel as degradable and antibacterial wound dressing for clinical treatment, but also provides a new strategy for developing low-cost, degradable, and antibacterial wound dressings and reducing antibiotic abuse and environmental pollution caused by medical waste.

Macrophage metabolic reprogramming-based diabetic infected bone defect/bone reconstruction though multi-function silk hydrogel with exosome release

Diabetic infected bone defects (DIBD) with abnormal immune metabolism are prone to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly-l-lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance against both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterial with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration.