In Situ Synthesis and Self-Assembly of Peptide-PEG Conjugates: A Facile Method for the Construction of Fibrous Hydrogels.

Peptide-based hydrogels have gained considerable attention as a compelling platform for various biomedical applications in recent years. Their attractiveness stems from their ability to seamlessly integrate diverse properties, such as biocompatibility, biodegradability, easily adjustable hydrophilicity/hydrophobicity, and other functionalities. However, a significant drawback is that most of the functional self-assembling peptides cannot form robust hydrogels suitable for biological applications. In this study, we present the synthesis of novel peptide-PEG conjugates and explore their comprehensive hydrogel properties. The hydrogel comprises double networks, with the first network formed through the self-assembly of peptides to create a ß-sheet secondary structure. The second network is established through covalent bond formation via N-hydroxysuccinimide chemistry between peptides and a 4-arm PEG to form a covalently linked network. Importantly, our findings reveal that this hydrogel formation method can be applied to other peptides containing lysine-rich sequences. Upon encapsulation of the hydrogel with antimicrobial peptides, the hydrogel retained high bacterial killing efficiency while showing minimum cytotoxicity toward mammalian cells. We hope that this method opens new avenues for the development of a novel class of peptide-polymer hydrogel materials with enhanced performance in biomedical contexts, particularly in reducing the potential for infection in applications of tissue regeneration and drug delivery.

Injectable Hydrogels of Amphiphilic Vitamin E Derivatives for Locoregional Chemotherapy.

Vitamin E derivatives are particularly effective in chemotherapy drug development because they are nontoxic, biocompatible, and selective. Among them, α-tocopheryl succinate (α-TOS) can act synergistically with some chemotherapeutic agents. However, its hydrophobicity limits its systemic administration, and localized formulations are not available. Herein, we developed an injectable hydrogel based on self-assembled micelles of a triblock amphiphilic derivative of α-TOS (PEG-2VES), in which doxorubicin (DOX) was encapsulated in the core of the micelles for combined chemotherapy. A molecule of α-TOS was grafted onto each end of poly(ethylene glycols) (PEGs) of different lengths. Hydrogels were prepared by dissolving the polymers or the DOX-loaded micelles in water at room temperature. The subcutaneously injected hydrogels kept their shape and sustainably released the payloads over 7 days without any noticeable inflammatory response. In vitro and in vivo results confirmed the synergistic antitumor effects of the hydrogel and loaded drug. Furthermore, DOX-loaded hydrogels showed greater therapeutic efficiency and fewer toxic side effects than DOX alone. Overall, this hydrogel acts as a multifunctional system that can deliver drug, improve the therapeutic effect, and minimize drug toxicity.

Hybrid Hydrogels from Nongelling Polymers Using a Fibrous Peptide Hydrogelator at Low Concentrations.

Nature-made hydrogels typically combine a wide range of multiscale fibers into biological composite networks, which offer an adaptive property. Inspired by nature, we report a facile approach to construct hybrid hydrogels from a range of natural or commercially available synthetic nongelling polymers (e.g., poly(ethylene glycol), poly(acrylic acid), carboxylated cellulose nanocrystal, and sodium alginate) at a concentration as low as 0.53 wt % using a nonionic fibrous peptide hydrogelator. Through simply mixing the peptide hydrogelator with a polymer aqueous solution, stable hybrid hydrogels can be formed with the concentration of hydrogelator at ∼0.05 wt %. The gel strength of the resulting hydrogels can be effectively modulated by the concentration, molecular weight, and terminal group of the polymer. We further demonstrate that the molecular interactions between the peptide hydrogelator and the polymer are very crucial for the formation of hybrid hydrogel, which synergically induce the gelation at considerably low concentrations. A peptide hydrogelator can be easily obtained by aminolysis of alkyl-oilgo(γ-benzyl-l-glutamate) samples. Live/Dead assays indicate low cytotoxicity of the hybrid hydrogel toward HeLa cells. Combining the low-cost, scalable synthesis, and biocompatibility, the prepared peptide hydrogelator presents a potential candidate to expand the scope of polymer hydrogels for biomedical applications and also shows considerable commercial significance.

Amoebicidal Activity of Poly-Epsilon-Lysine Functionalized Hydrogels.

Purpose: To determine the amoebicidal activity of functionalized poly-epsilon-lysine hydrogels (pɛK+) against Acanthamoeba castellanii. Methods: A. castellanii trophozoites and cysts were grown in the presence of pɛK solution (0-2.17 mM), pɛK or pɛK+ hydrogels, or commercial hydrogel contact lens (CL) for 24 hours or 7 days in PBS or Peptone-Yeast-Glucose (PYG) media (nutrient-deplete or nutrient-replete cultures, respectively). Toxicity was determined using propidium iodide and imaged using fluorescence microscopy. Ex vivo porcine corneas were inoculated with A. castellanii trophozoites ± pɛK, pɛK+ hydrogels or commercial hydrogel CL for 7 days. Corneal infection was assessed by periodic acid-Schiff staining and histologic analysis. Regrowth of A. castellanii from hydrogel lenses and corneal discs at 7 days was assessed using microscopy and enumeration. Results: The toxicity of pɛK+ hydrogels resulted in the death of 98.52% or 83.31% of the trophozoites at 24 hours or 7 days, respectively. The toxicity of pɛK+ hydrogels resulted in the death of 70.59% or 82.32% of the cysts in PBS at 24 hours or 7 days, respectively. Cysts exposed to pɛK+ hydrogels in PYG medium resulted in 75.37% and 87.14% death at 24 hours and 7 days. Ex vivo corneas infected with trophozoites and incubated with pɛK+ hydrogels showed the absence of A. castellanii in the stroma, with no regrowth from corneas or pɛK+ hydrogel, compared with infected-only corneas and those incubated in presence of commercial hydrogel CL. Conclusions: pɛK+ hydrogels demonstrated pronounced amoebicidal and cysticidal activity against A. castellanii. pɛK+ hydrogels have the potential for use as CLs that could minimize the risk of CL-associated Acanthamoeba keratitis.

High-Performance Smart Hydrogels with Redox-Responsive Properties Inspired by Scallop Byssus.

Smart hydrogels with versatile properties, including a tunable gelation time, nonswelling attributes, and biocompatibility, are in great need in the biomedical field. To meet this urgent demand, we explored novel biomaterials with the desired properties from sessile marine organisms. To this end, a novel protein, Sbp9, derived from scallop byssus was extensively investigated, which features typical epidermal growth factor-like (EGFL) multiple repetitive motifs. Our current work demonstrated that the key fragment of Sbp9 (calcium-binding domain (CBD) and 4 EGFL repeats (CE4)) was able to form a smart hydrogel driven by noncovalent interactions and facilitated by disulfide bonds. More importantly, this smart hydrogel demonstrates several desirable and beneficial features, which could offset the drawbacks of typical protein-based hydrogels, including (1) a redox-responsive gelation time (from <1 to 60 min); (2) tunable mechanical properties, nonswelling abilities, and an appropriate microstructure; and (3) good biocompatibility and degradability. Furthermore, proof-of-concept demonstrations showed that the newly discovered hydrogel could be used for anticancer drug delivery and cell encapsulation. Taken together, a smart hydrogel inspired by marine sessile organisms with desirable properties was generated and characterized and demonstrated to have extensive applicability potential in biomedical applications, including tissue engineering and drug release.

Preparation of smart PVP/HPMC based IPN hydrogel, its characterization and toxicity evaluation.

In this study, the interpenetrating polymeric network (IPN) were fabricated via free radical polymerization using polymers hydroxypropyl methylcellulose (HPMC), Polyvinylpyrrolidone (PVP) and monomer Methacrylic acid (MAA) and also investigated their influence by changing their concentrations. The developed polymeric network is crosslinked via N' N' -methylene bis-acrylamide (MBA). Different characterizations have been performed to analyze fabricated interpenetrating polymeric network structure i.e., Scanning Electron Microscopy (SEM), X-ray Powder Diffraction (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC). Letrozole (LTZ) was loaded as a model drug in the developed system. Swelling dynamics as well as drug release behavior were thoroughly examined. FTIR studies corroborated the formation of interpenetrating polymeric network. SEM uncovered porous structure while TGA depicted enhanced thermal stability of polymeric network. PXRD depicted amorphous dispersion of LTZ. Swelling dynamics as well as LTZ release behavior from developed interpenetrating polymeric network hydrogels were dependent upon pH of the medium and concentration of pure reactants employed. Higuchi model was best fit to regression coefficient which indicated diffusion controlled mechanism of drug release. Acute oral toxicity study depicted no mortality or any signs relating to acute toxicity throughout the whole observed period. Hence, the designed interpenetrating polymeric network might turn out to be a safe and a potential carrier system for the delivery of LTZ in the treatment of breast cancer (BC).

Super-fast in situ formation of hydrogels based on multi-arm functional polyethylene glycols as endotamponade substitutes.

Polymer-based hydrogels used in the vitreous cavity could lead to an unsatisfactory gel-forming state, uncontrollable swelling, and potential cytotoxicity. Their application can significantly impair the filling effect and cause severe side effects in the surrounding tissues. To address the concerns, a poly(ethylene glycol)-engineered hydrogel capable of fast in situ gel formation (less than 1 min), with an ultralow swelling ratio and no cytotoxicity in the rabbits' eyes, was constructed as a vitreous substitute. The multi-arm polyethylene glycols (PEGs) modified with functional groups (thiol and maleimide) possess high reaction efficiency in the vitreous cavity and present excellent biomimetic characteristics of the natural vitreous humor in vitro. After injection with a double syringe via a 25-gauge needle in the eyes of rabbits for 6 months, the hydrogel functioned as an artificial vitreous body that could highly promote retinal detachment repair, with excellent biocompatibility and high transparency, and without bio-degradation or ocular complications. Collectively, the fast in situ forming hydrogel could achieve quick and good filling in the vitreous cavity without cytotoxicity, which makes it a promising long-term endotamponade substitute.

Coassembly Behavior and Rheological Properties of a ß-Hairpin Peptide with Dicarboxylates.

To understand the molecular interaction mechanism and develop peptide-based hydrogels, a ß-hairpin peptide CBHH was used as the model peptide, and its coassembly performance with succinic, malic, and tartaric dicarboxylates has been investigated with circular dichroism spectroscopy (CD) and atomic force microscopy (AFM). The rheological properties and cell culture performance of the coassembled hydrogels have also been assessed. The results showed that the dicarboxylates could induce the folding and self-assembly of the ß-hairpin peptide and promote its gelation at low pH. The effects of the dicarboxylates on peptide self-assembly and hydrogel properties were correlated to their hydroxyl group number. The toxicity of the hydrogel has been assessed with NIH-3T3 cells by MTT and Calcein-AM/PI experiments, and it was confirmed that the hydrogel was biocompatible and could be used as cell culture scaffolds. We hope that this study would provide a novel way for biomaterial fabrication in cell and tissue engineering.

Fabrication of a Silk Sericin Hydrogel System Delivering Human Lactoferrin Using Genetically Engineered Silk with Improved Bioavailability to Alleviate Chemotherapy-Induced Immunosuppression.

Chemotherapy is one of the main treatments for cancer; however, it usually causes severe atrophy of immune organs and self-immunity damage to patients. Human lactoferrin (hLF) is a multiple biofunctional protein in regulating the immune response and thus holds great promise to alleviate chemotherapy-caused immunosuppression. However, a sufficient hLF resource and efficient delivery of hLF remain a challenge. Here, we provide a useful strategy to simultaneously solve these two problems. A silk sericin hydrogel system delivering recombinant hLF (SSH-rhLF) was fabricated to alleviate the chemotherapeutic drug-caused side effects by rhLF-carrying silk cocoons, which were cost-effectively produced by a transgenic silkworm strain as the resource. SSH-rhLF with a uniform porous microstructural morphology, a dominant ß-sheet internal structure, adjustable concentration and sustainable release of the rhLF, and non-cytotoxicity properties was demonstrated. Interestingly, the sericin hydrogel showed effective protection of the rhLF from degradation in the stomach and small intestine, thus prolonging the bioactivity and bioavailability of rhLF. As a result, the oral administration of SSH-rhLF with a low rhLF dose showed significant therapeutic effects on enhancing the immune organs of cyclophosphamide (CTX)-treated mice by protecting the splenic follicles, promoting the expression of immunoregulatory factors, and recovering the intestinal flora family from CTX-induced imbalance, which were similar to those achieved by oral administration of a high dose of free hLF in the solution form. The results suggest that the strategy of producing rhLF silk cocoons via feeding transgenic silkworms overcomes well the shortage of rhLF resources, improves the bioavailability of oral rhLF, and alleviates the side effects of chemotherapeutic drugs on immune organs. The oral SSH-rhLF will be promising for applications in cancer chemotherapy and immunity enhancement of patients.

Injectable Micelle-Incorporated Hydrogels for the Localized Chemo-Immunotherapy of Breast Tumors.

Although immune checkpoint blockade (ICB) holds potential for the treatment of various tumors, a considerable proportion of patients show a limited response to ICB therapy due to the low immunogenicity of a variety of tumors. It has been shown that some chemotherapeutics can turn low-immunogenic tumors into immunogenic phenotypes by inducing a cascade of immune responses. In this paper, we synthesized an injectable micelle-incorporated hydrogel, which was able to sequentially release the chemotherapeutic gemcitabine (GEM) and the hydrophobic indoleamine 2, 3-dioxygenase inhibitor, d-1-methyltryptophan (d-1MT) at tumor sites. The hydrogel was formed via the thiol-ene click reaction between the thiolated chondroitin sulfate and the micelle formed by amphiphilic methacrylated Pluronic F127, in which hydrophobic d-1MT was encapsulated in the core of the F127 micelles and the hydrophilic GEM was dispersed in the hydrogel network. The successive release of chemotherapeutics and immune checkpoint inhibitors at tumor tissues will first promote the infiltration of cytotoxic T lymphocytes and subsequently induce a robust antitumor immune response, ultimately exerting a synergetic therapeutic efficacy. In a 4T1 tumor-bearing mice model, our results showed that the combination of chemotherapy and immunotherapy through the micelle-incorporated hydrogel triggered an effective antitumor immune response and inhibited tumor metastasis to the lung. Our results highlight the potential of the injectable micelle-incorporated hydrogel for the localized chemo-immunotherapy in the treatment of breast tumors.

Bioactive chitosan biguanidine-based injectable hydrogels as a novel BMP-2 and VEGF carrier for osteogenesis of dental pulp stem cells.

Nowadays, vascularization and mineralization of bone defects is the main bottleneck in the bone regeneration field that is needed to be overcome and developed. Here, we prepared novel in-situ formed injectable hydrogels based on chitosan biguanidine and carboxymethylcellulose loaded with vascular endothelial growth factor (VEGF) and recombinant Bone morphogenetic protein 2 (BMP-2) and studied its influence on osteoblastic differentiation of dental pulp stem cells (DPSCs). The sequential release behavior of the VEGF and BMP-2 from hydrogels adjusted with the pattern of normal human bone growth. MTT assay exhibited that these hydrogels were non-toxic and significantly increased DPSCs proliferation. The Real-time PCR and Western blot analysis on CG11/BMP2-VEGF showed significantly higher gene and protein expression of ALP, COL1α1, and OCN. These results were confirmed by mineralization assay by Alizarin Red staining and Alkaline phosphatase enzyme activity. Based on these evaluations, these hydrogel holds potential as an injectable bone tissue engineering platform.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Production of wheat germ oil containing multilayer hydrogel dressing.

A composite wound dressing has been developed by combining different layers consisting of polymers and textiles. Wheat germ oil (WGO) loaded hydrogels have successfully formed on textile nonwovens by cross-linking sodium alginate (SA) with poly(ethylene glycol) diglycidyl ether (PEGDGE). Following freeze-drying, textile-hydrogel composites have been examined according to their physical properties, pH, fluid handling capacity, water vapour permeability, morphology, chemical structure, and cytotoxicity. Hydrogels containing WGO swelled less than pristine hydrogels. Samples with 1% WGO and no WGO showed swelling of 5.9 and 10.5 g/g after 8 h. WGO inclusion resulted in reduced, but more stable fluid handling properties, with more uniform pore distribution (100-200 µm). Moreover, the proliferation of NIH/3T3 cells significantly improved with 1% WGO contained hydrogels. Also, commercial self-adhesive dressings that secure the hydrogels to the wound area were investigated regarding transfer properties. The proposed product demonstrated 8.05 cm3/cm2/s and 541.37 g/m2/day air and water vapour permeability.

Fabrication of self-healing pectin/chitosan hybrid hydrogel via Diels-Alder reactions for drug delivery with high swelling property, pH-responsiveness, and cytocompatibility.

Self-healing hydrogels with pH-responsiveness could protect loaded drugs from being destroyed till it arrives to the target. The pectin-based hydrogel is a candidate due to the health benefit, anti-inflammation, antineoplastic activity, nontoxicity, and biospecific degradation, et al. However, the abundant existence of water-soluble branched heteropolysaccharide chains influenced its performance resulting in limitation of the potential. In the present study, we prepared a series of self-healing pectin/chitosan hydrogels via the Diels-Alder reaction. Moreover, pectin/chitosan composite hydrogel was prepared as a contrast. By comparison, it can be seen that the Diels-Alder reaction greatly improved the cross-linking density of hydrogels. The self-healing experiments showed excellent self-healing performance. In different swelling mediums, significant transformation in the swelling ratio was shown, indicating well-swelling property, pH- and thermo-responsiveness. The drug loading and release studies presented high loading efficiency and sustained release performance. The cytotoxicity assay that showed a high cell proliferation ratio manifested great cytocompatibility.

Polypseudorotaxane and polydopamine linkage-based hyaluronic acid hydrogel network with a single syringe injection for sustained drug delivery.

Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection.

Enhanced anti-cancer activity by localized delivery of curcumin form PVA/CNCs hydrogel membranes: Preparation and in vitro bioevaluation.

This study targets to develop curcumin-loaded polyvinyl alcohol/cellulose nanocrystals (PVA/CNCs) membrane as localized delivery system for breast/liver cancer. A novel strategy was developed for enhancing encapsulation capacity and maximizing therapeutic efficiency of curcumin-loaded PVA/CNCs membranes. Membranes were prepared by solution-casting method using citric acid as crosslinker. SEM revealed that PVA/CNCs ratio (80:20) was chosen as the optimum for loading curcumin. FT-IR indicated that, curcumin was incorporated into PVA/CNCs in amorphous-phase via intermolecular hydrogen bond between curcumin and membrane components. Curcumin showed biphasic-release through burst-release of 41% of curcumin during the first hour, followed by sustained-release of 70% and 94% during 24 h and 48 h, respectively. In vitro cytotoxicity of PVA/CNCs/Curcumin membrane exhibited a selective inhibition proliferation of breast and liver cancer cells in a concentration-dependent without any toxic effect on normal cells. At high concentration (8 mg/ml) of PVA/CNCs/Curcumin, reduced viability to 35% and 7% of MCF-7 and Huh-7 cells, respectively; meanwhile high HFB-4 normal cell viability ≥80% was investigated. Antimicrobial activity of PVA/CNCs/Curcumin was investigated by multi-drug-resistant strains, and MIC values. PVA/CNCs/Curcumin membranes with concentration (40 mg/ml) showed broad-spectrum antimicrobial activities, thus inhibited ~96-99% of microbial growth. PVA/CNCs/Curcumin membranes could be as promised anti-infective biomaterials for breast and liver cancer wound healing.

Biomimetic epidermal sensors assembled from polydopamine-modified reduced graphene oxide/polyvinyl alcohol hydrogels for the real-time monitoring of human motions.

Conductive hydrogel-based epidermal strain sensors can generate repeatable electrical changes upon mechanical deformations for indication of the skin's physiological condition. However, this remains challenging for many conductive hydrogel sensors due to biomechanical mismatch with skin tissues and an unstable resistance variation response, resulting in non-conformable deformations with the epidermis and dermis, and consequently generating inaccurate monitoring of human movements. Herein, a conductive hydrogel that highly matches the skin is fabricated from dynamically hydrogen-bonded nanocrystallites of polydopamine-modified reduced graphene oxide (PDA-rGO) nanosheets composited with polyvinyl alcohol, namely the PDA-rGO/PVA hydrogel. PDA-rGO provides a large number of dynamic hydrogen-bonding interactions in the hydrogel, resulting in a skin-matching modulus (78 kPa) and stretchability. Moreover, the resultant hydrogel possesses excellent cytocompatibility and conductivity (0.87 S m-1), high sensitivity (gauge factor of compression: 20) at low strain and outstanding linearity at high strain as well as a stable resistance variation response. These desirable properties enable the application of the PDA-rGO/PVA hydrogel as a skin-friendly wearable sensor for real-time and accurate detection of both large-scale joint movements and tiny physiological signals, including the bending and relaxing of fingers, the wrist, elbow and knee joints, and wrist pulse and swallowing. Moreover, this hydrogel is integrated into a 2D sensor array that monitors strains or pressures in two dimensions, which is promising for electronic skin, biosensors, human-machine interfaces, and wearable electronic devices.

Agar/κ-carrageenan/montmorillonite nanocomposite hydrogels for wound dressing applications.

In this study, agar/κ-carrageenan/montmorillonite (MMT) hydrogels were prepared to examine their usability as wound dressing materials and to see the effect of MMT amount on some properties of agar/κ-carrageenan hydrogel materials. Hydrogels were characterized by SEM-EDX, TEM and DSC analyses. By increasing the MMT content within hydrogel matrix from 0% to 5%, the decomposition temperature of the hydrogel material was increased from 256.6 °C to 262.1 °C. Swelling amount of hydrogels in d-glucose solution (2682%) was found to be much higher compared with other physiological solutions such as physiological saline solution (937%), synthetic urine solution (746%) and simulated wound fluid (563%). The release studies of analgesic lidocaine hydrochloride (LDC) and antibiotic chloramphenicol (CLP) drugs from hydrogel systems demonstrated that the release amount of LDC and CLP from hydrogels could be controlled by MMT amount within hydrogel matrix. The concentrations of drugs within hydrogel sample stored at 4 °C for 6 months did not exhibit a significant change. Hydrogel materials containing CLP exhibited good antibacterial activity against E. coli and S. aureus. Cytotoxicity test results indicated that hydrogels were biocompatible with MG-63 cells. The ultimate compressive stress of agar/κ-carrageenan hydrogel with LDC and CLP and agar/κ-carrageenan/MMT hydrogel including 5% MMT with LDC and CLP was measured as 38.30 kPa and 47.70 kPa, respectively. The experimental results revealed that prepared agar/κ-carrageenan and agar/κ-carrageenan/MMT hydrogels have great potential for wound care applications.

Injectable polypeptide-engineered hydrogel depot for amplifying the anti-tumor immune effect induced by chemo-photothermal therapy.

The immunosuppressive tumor microenvironment has caused great obstacles to tumor immunotherapy, especially where less tumor-associated antigens are released from tumor sites. Herein, a Ag2S QD/DOX/Bestatin@PC10ARGD genetically engineered polypeptide hydrogel PC10ARGD as a sustained-release material was developed for mammary carcinoma treatment. A near-infrared silver sulfide (Ag2S) QD as a photosensitizer was encapsulated into the hydrophobic cavity formed by the self-assembly of the polypeptide nanogel (PC10ARGD) for photothermal therapy. The water-soluble drug DOX and Bestatin were integrated into the PC10ARGD hydrogel. The photothermal effect could trigger the sustained release of the DOX, which could be applied to initiate in situ vaccination. Bestatin as an immune-adjuvant drug could amplify the body's immune function. The results of in vivo therapy tests exhibited that the Ag2S QD/DOX/Bestatin@PC10ARGD hydrogel with laser irradiation could activate anti-tumor immune effects that inhibit the growth of primary tumors and distal lung metastatic nodules. Meanwhile, a safer lower-temperature with multiple laser irradiation treatment strategy exhibited more effective tumor-killing performance (84.4% tumor inhibition rate) and promoted the penetration of immune cells into the tumor tissue. The CD8+ and CD4+ cytotoxic T cells ratio was increased by 5.3 and 10 times, respectively, thus exhibiting a good prognostic signal. The multifunctional polypeptide hydrogel as a green manufacturing and engineering material is promising to serve as a cancer vaccine for anticancer applications.

Bioresponsive supramolecular hydrogels for hemostasis, infection control and accelerated dermal wound healing.

Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including hemostasis and anti-bacterial activity are essential for successful wound healing; however, designing ideal materials is still challenging. Herein, we demonstrate the fabrication of a biodegradable, temperature-pH dual responsive supramolecular hydrogel (SHG) scaffold based on sodium alginate/poly(N-vinyl caprolactam) (AG/PVCL) through free radical polymerization and the subsequent chemical and ionic cross-linking. A natural therapeutic molecule, tannic acid (TA)-incorporated SHG (AG/PVCL-TA), was also fabricated and its hemostatic and wound healing efficiency were studied. In the AG/PVCL-TA system, TA acts as a therapeutic molecule and also substitutes as an effective gelation binder. Notably, the polyphenol-arm structure and diverse bonding abilities of TA can hold polymer chains through multiple bonding and co-ordinate cross-linking, which were vital in the formation of the mechanically robust AG/PVCL-TA. The SHG formation was successfully balanced by varying the composition of SA, VCL, TA and cross-linkers. The AG/PVCL-TA scaffold was capable of releasing a therapeutic dose of TA in a sustained manner under physiological temperature-pH conditions. AG/PVCL-TA displayed excellent free radical scavenging, anti-inflammatory, anti-bacterial, and cell proliferation activity towards the 3T3 fibroblast cell line. The wound healing performance of AG/PVCL-TA was further confirmed in skin excision wound models, which demonstrated the potential application of AG/PVCL-TA for skin regeneration and rapid wound healing.