Synthesis and characterization of in situ cross-linked hydrogel based on self-assembly of thiol-modified chitosan with PEG diacrylate using Michael type addition

A novel injectable in situ cross-linked hydrogel has been designed via Michael type addition between thiol-modified chitosan (CS-NAC) and PEG diacrylate (PEGDA). Hydrogel was rapidly formed in situ under physiological conditions. The gelation time depended on the content of free thiols in CS-NAC, temperature, and concentration of CS-NAC and PEGDA. Thermogravimetric analysis showed the thermal stabilities of hydrogels. SEM observation results confirmed a porous 3D structure. Rheological studies showed that the cross-linking density and elasticity of hydrogel had a correlation to the content of CS-NAC and PEGDA. Swelling studies revealed that these hydrogels had a high initial swelling and were degradable under physiological conditions. And swelling was highly temperature-dependent and was directly related to the amount of cross-linking. Biological activities of the hydrogels were evaluated by in vitro cell compatibility on HDFs and A549 cells and the results indicated that the hydrogel was biocompatible.     

Polypropylene oxide/polyethylene oxide-cellulose hybrid nanocomposite hydrogels as drug delivery vehicle

This article deals with the synthesis of hybrid nanocomposite hydrogels through the combination of cellulose (C), polypropylene oxide/poly ethylene oxide (PPO/PEO), and silver nanoparticles (AgNPs) by in situ polymerization technique for the in vitro release of ornidazole drugs. The structure of the resulted materials is identified using SEM, XRD, FTIR, XPS, and TGA spectroscopic techniques. The resulting structure, morphology, thermo responsive property, water retention, and swelling behavior of hydrogels are investigated. The rheological measurement is studied to establish the enhancement of the viscoelasticity and stiffness of hydrogels. The antibacterial activity of the biodegradable silver hybrid nanocomposite hydrogel is investigated by inhibition zone method against gram positive and negative bacteria. Maximum drug release of 96.4% is recorded at 7.4 pH in 5 h. The biocompatibility and cytotoxicity of the hybrid nanocomposite hydrogel are verified using mouse fibroblast cell line L-929 (ATCC CCL-1) cells for their possible use as controlled drug delivery vehicles. The nontoxic nature makes the materials more biocompatible and suitable to apply in the biological systems. Therefore, nontoxic and biocompatible natures of present materials with improved thermal and rheological properties support for their possible uses as drug delivery vehicles.     

Personalized Single‐Cell Encapsulation Using E‐Jet 3D Printing with AC‐Pulsed Modulation

With the growing therapeutic importance of cell microcarriers, there has been a rise in the need to develop technologies that facilitate efficient microencapsulation of cells, currently limited by a lack of straightforward and low‐cost strategies for single‐cell isolation and printing. Thus, the aim of this study is to develop a gentle and cell‐compatible electro‐hydrodynamic jet 3D printing technique to facilitate the efficient microencapsulation of cells in hydrogel microspheres, and investigate the effects of parameters (flow rate, voltage frequency, nozzle diameter, working distance, and substrate velocity) on the printing process. Stable microspheres are obtained by regulating these parameters to balance various forces, with control of their diameters in the range of 100–600 µm. The study demonstrates that under optimized conditions, the technique is able to successfully encapsulate cells within hydrogel microspheres with high viability over a wide range of diameters. This 3D printing technique expands the potential utility of microspheres into additional biological applications, such as cancer biology and drug screening. It can also be used as an effective platform for the production of tumor spheroids, generating multicellular spheroid models in vitro or for injectable cell delivery.     

Short-peptide-based molecular hydrogels: novel gelation strategies and applications for tissue engineering and drug delivery

Molecular hydrogels hold big potential for tissue engineering and controlled drug delivery. Our lab focuses on short-peptide-based molecular hydrogels formed by biocompatible methods and their applications in tissue engineering (especially, 3D cell culture) and controlled drug delivery. This feature article firstly describes our recent progresses of the development of novel methods to form hydrogels, including the strategy of disulfide bond reduction and assistance with specific protein-peptide interactions. We then introduce the applications of our hydrogels in fields of controlled stem cell differentiation, cell culture, surface modifications of polyester materials by molecular self-assembly, and anti-degradation of recombinant complex proteins. A novel molecular hydrogel system of hydrophobic compounds that are only formed by hydrolysis processes was also included in this article. The hydrogels of hydrophobic compounds, especially those of hydrophobic therapeutic agents, may be developed into a carrier-free delivery system for long term delivery of therapeutic agents. With the efforts in this field, we believe that molecular hydrogels formed by short peptides and hydrophobic therapeutic agents can be practically applied for 3D cell culture and long term drug delivery in near future, respectively.     

A novel drug loading and release from a thermoresponsive hydrogel formed in situ emulsion polymerization

A facile thermoresponsive injectable hydrogel is prepared from stearyl methacrylate (SMA) and N-isopropyl acrylamide (NIPAM) copolymers via reversible addition-fragmentation chain-transfer (RAFT) emulsion polymerization method. By regulating the content of the oil phase, emulsions with divergent properties are obtained. The yield stress and the viscosity results of the emulsions increase evidently as the initial content of the oil phase increase from 10 to 40%. The microstructures of 10% oil content sample (SN10) is seen as a dispersed particle whereas 20, 30, and 40% oil content samples (SN20, SN30, and SN40) appear as aggregated particles in a dilute solution that shows the microscopical phase transitions of the emulsions. Increasing the temperature from 15 to 45 °C, phase separation takes place, the emulsions contract to squeeze the water. A sharp decrease in particle size is noticed when the temperature increase from 30 to 35 °C. In this point, hydrophilic drug procaine is loaded and release experiments are conducted using thermoresponsive injectable hydrogel. The drug loading and release results are evaluated using the Weibull distribution model and the Fick's law of diffusion that precisely works out. A thermoresponsive injectable hydrogel offers an efficient, cost-effective, and scalable approach towards controlled release of drugs. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 137, 48669.     

Efficient inhibition of colorectal peritoneal carcinomatosis by drug loaded micelles in thermosensitive hydrogel composites

In this work, we aim to develop a dual drug delivery system (DDDS) of self-assembled micelles in thermosensitive hydrogel composite to deliver hydrophilic and hydrophobic drugs simultaneously for colorectal peritoneal carcinomatosis (CRPC) therapy. In our previous studies, we found that poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC) copolymers with different molecular weight and PEG/PCL ratio could be administered to form micelles or thermosensitive hydrogels, respectively. Therefore, the DDDS was constructed from paclitaxel (PTX) encapsulated PCEC micelles (PTX-micelles) and a fluorouracil (Fu) loaded thermosensitive PCEC hydrogel (Fu-hydrogel). PTX-micelles were prepared by self-assembly of biodegradable PCEC copolymer (M(n) = 3700) and PTX without using any surfactants or excipients. Meanwhile, biodegradable and injectable thermosensitive Fu-hydrogel (M(n) = 3000) with a lower sol-gel transition temperature at around physiological temperature was also prepared. The obtained PTX-micelles in thermosensitive Fu-hydrogel (PTX-micelles-Fu-hydrogel) composite is a free-flowing sol at ambient temperature and rapidly turned into a non-flowing gel at physiological temperature. In addition, the results of cytotoxicity, hemolytic study, and acute toxicity evaluation suggested that the PTX-micelles-Fu-hydrogel was non-toxic and biocompatible. In vitro release behaviors of PTX-micelles-Fu-hydrogel indicated that both PTX and Fu have a sustained release behavior. Furthermore, intraperitoneal application of PTX-micelles-Fu-hydrogel effectively inhibited growth and metastasis of CT26 peritoneal carcinomatosis in vivo (p < 0.001), and induced a stronger antitumor effect than that of Taxol? plus Fu (p < 0.001). The pharmacokinetic study indicated that PTX-micelles-Fu-hydrogel significantly increased PTX and Fu concentration and residence time in peritoneal fluids compared with Taxol? plus Fu group. Thus, the results suggested the micelles-hydrogel DDDS may have great potential clinical applications.     

Photo-Polymerization Damage Protection by Hydrogen Sulfide Donors for 3D-Cell Culture Systems Optimization

Photo-polymerized hydrogels are ideally suited for stem-cell based tissue regeneration and three dimensional (3D) bioprinting because they can be highly biocompatible, injectable, easy to use, and their mechanical and physical properties can be controlled. However, photo-polymerization involves the use of potentially toxic photo-initiators, exposure to ultraviolet light radiation, formation of free radicals that trigger the cross-linking reaction, and other events whose effects on cells are not yet fully understood. The purpose of this study was to examine the effects of hydrogen sulfide (H₂S) in mitigating cellular toxicity of photo-polymerization caused to resident cells during the process of hydrogel formation. H₂S, which is the latest discovered member of the gasotransmitter family of gaseous signalling molecules, has a number of established beneficial properties, including cell protection from oxidative damage both directly (by acting as a scavenger molecule) and indirectly (by inducing the expression of anti-oxidant proteins in the cell). Cells were exposed to slow release H₂S treatment using pre-conditioning with glutathione-conjugated-garlic extract in order to mitigate toxicity during the photo-polymerization process of hydrogel formation. The protective effects of the H₂S treatment were evaluated in both an enzymatic model and a 3D cell culture system using cell viability as a quantitative indicator. The protective effect of H₂S treatment of cells is a promising approach to enhance cell survival in tissue engineering applications requiring photo-polymerized hydrogel scaffolds.     

An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.     

Three-Dimensional Cell Culture Models to Investigate Oral Carcinogenesis: A Scoping Review

Three-dimensional (3-D) cell culture models, such as spheroids, organoids, and organotypic cultures, are more physiologically representative of the human tumor microenvironment (TME) than traditional two-dimensional (2-D) cell culture models. They have been used as in vitro models to investigate various aspects of oral cancer but, to date, have not be widely used in investigations of the process of oral carcinogenesis. The aim of this scoping review was to evaluate the use of 3-D cell cultures in oral squamous cell carcinoma (OSCC) research, with a particular emphasis on oral carcinogenesis studies. Databases (PubMed, Scopus, and Web of Science) were systematically searched to identify research applying 3-D cell culture techniques to cells from normal, dysplastic, and malignant oral mucosae. A total of 119 studies were included for qualitative analysis including 53 studies utilizing spheroids, 62 utilizing organotypic cultures, and 4 using organoids. We found that 3-D oral carcinogenesis studies had been limited to just two organotypic culture models and that to date, spheroids and organoids had not been utilized for this purpose. Spheroid culture was most frequently used as a tumorosphere forming assay and the organoids cultured from human OSCCs most often used in drug sensitivity testing. These results indicate that there are significant opportunities to utilize 3-D cell culture to explore the development of oral cancer, particularly as the physiological relevance of these models continues to improve.     

Thermosensitive chitosan hydrogel for implantable drug delivery: Blending PVA to mitigate body response and promote bioavailability

Thermosensitive hydrogels promise to be the injectable implants for long-term controlled drug release; however, body response to the implanted hydrogels and its unpredictable impacts on drug release complicates their applications. In the present study, hydrophilic polymer poly(vinyl alcohol) (PVA) was blended into the thermosensitive hydrogel composed of chitosan and glycerophosphate to mitigate the body responses and promote the drug bioavailability. The effects of PVA on the surface properties of the hydrogel were evaluated by zeta-potential, water contact angle, and cell attachment. Body responses were explored by histological examination via subcutaneously implanting the hydrogels into Sprague-Dawley rats. Drug release in vivo and bioavailability were determined with cyclosporine A (CsA) employed as the model drug. The results showed that, on one hand, the presence of PVA improved the surface hydrophilicity of the hydrogel and inhibited the cell attachment on the hydrogel, which alleviated the further cell infiltration and tissue integration in body; and on the other hand, blending of PVA led to the more rapid gel formation and more compact network, which resisted the dehydration and survived the hydrogel from cell division. These advantages benefited the controlled release and absorption of CsA, and contributed to the higher drug bioavailability. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Hydrophobicities and antibacterial activities of silicone polyester/titanium dioxide composites on nylon fabrics after argon plasma treatment

To be more biocompatible, poly(N-isopropyl acrylamide) (PNIPAM) hydrogel, as a typical temperature-sensitive hydrogel, is expected to be linked with other materials of excellent biocompatibility. For this propose, poly(N-isopropyl acrylamide)-block-poly(3-O-allyl-α-D-glucose) (PNIPAM-b-POAG), a new diblock copolymer, was successfully synthesized from N-isopropyl acrylamide (NIPAM) and 3-O-allyl-1,2:5,6-di-O-isopropynylene-α-D-glucose (OAIG) via reversible addition-fragmentation chain transfer (RAFT) polymerization in the presence of cumyl dithiobenzoate (CDB). PNIPAM-b-POAG was characterized byFourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (¹H NMR) spectroscopy, and gel permeation chromatography (GPC). The critical micelle concentration (CMC) of the copolymer was 0.045 mg/ml measured by fluorescence spectroscopy. The copolymer solution exhibited a reversible sol-gel phase transitions with the increase or decrease of temperature. An in situ gel formed rapidly after subcutaneously injecting the copolymer solution into a Sprague Dawley (SD) rat, which indicated the copolymer has a good injectable property. The in vitro release result showed that methylene blue (MB) as a model was sustainably released by the temperature-sensitive PNIPAM-b-POAG diblock copolymer at 37 °C within 120 h. The copolymer showed no apparent cytotoxicity on L929 cells by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The novel temperature-sensitive hydrogel is a promising candidate for drug delivery.     

In situ-forming injectable hydrogels for regenerative medicine

Regenerative medicine involves interdisciplinary biomimetic approaches for cell therapy and tissue regeneration, employing the triad of cells, signals, and/or scaffolds. Remarkably, the field of therapeutic cells has evolved from the use of embryonic and adult stem cells to the use of induced pluripotent stem cells. For application of these cells in regenerative medicine, cell fate needs to be carefully controlled via external signals, such as the physical properties of an artificial extracellular matrix (ECM) and biologically active molecules in the form of small molecules, peptides, and proteins. It is therefore crucial to develop biomimetic scaffolds, reflecting the nanoenvironment of three-dimensional (3D) ECM in the body. Here, we describe in situ-forming injectable hydrogel systems, prepared using a variety of chemical crosslinkers and/or physical interactions, for application in regenerative medicine. Selective and fast chemical reactions under physiological conditions are prerequisites for in situ formation of injectable hydrogels. These hydrogels are attractive for regenerative medicine because of their ease of administration, facile encapsulation of cells and biomolecules without severe toxic effects, minimally invasive treatment, and possibly enhanced patient compliance. Recently, the Michael addition reaction between thiol and vinyl groups, the click reaction between bis(yne) molecules and multiarm azides, and the Schiff base reaction have been investigated for generation of injectable hydrogels, due to the high selectivity and biocompatibility of these reactions. Noncovalent physical interactions have also been proposed as crosslinking mechanisms for in situ forming injectable hydrogels. Hydrophobic interactions, ionic interactions, stereocomplex formation, complementary pair formation, and host–guest interactions drive the formation of 3D polymeric networks. In particular, supramolecular hydrogels have been developed using the host–guest chemistry of cyclodextrin (CD) and cucurbituril (CB), which allows highly selective, simple, and biocompatible crosslinking. Molecular recognition and complex formation of supramolecules, without the need for additional additives, have been successfully applied to the 3D network formation of polymer chains. Finally, we review the current state of the art of injectable hydrogel systems for application in regenerative medicine, including cell therapy and tissue regeneration.     

Amylopectin Multiple Aldehyde Crosslinked Hydrogel as an Injectable and Self‐Healing Cell Carrier for Bone Tissue Engineering

Despite excellent processing and biological properties of gelatin for use as a cell carrier, none of the gelatin‐based hydrogel cell carriers reported to date offer all characteristics including quick formation, injectability, self‐healing, and durability, which are simultaneously required for an ideal system. Here, a gelatin‐based hydrogel with dynamic Schiff base linkages, so‐called “dynamic hydrogel,” as an injectable cell carrier consisting of gelatin and amylopectin multiple aldehyde (AMPA), with all the required characteristics is reported. Biocompatibility and osteoinductivity of the hydrogel are verified through the culture of human bone marrow‐derived mesenchymal stem cells (hBMSCs). As live/dead results show, hBMSCs are alive and highly viable ≈85–90% within the hydrogel after 5 days. According to bromodeoxyuridine cell proliferation assay, a significant increase in the number of the cells seeded in the hydrogel confirms its clinical significance for cell therapy. Most importantly, histological visualization using Mason's Trichrome staining indicates secretion of extracellular matrix around the cells loaded in the hydrogel and also expression level evaluation of the crucial osteogenic markers, confirms that the hydrogel can provide osteoinductive support for osteocyte differentiation of hBMSCs after 14 days. Therefore, this hydrogel provides more progress on the path toward bone tissue engineering and further treatment of bone diseases.     

Fabrication and Characterisation of a Photo-Responsive,Injectable Nanosystem for Sustained Delivery of Macromolecules

The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of ≥80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.     

Promoted Proliferation of Hematopoietic Stem Cells Enabled by a Hyaluronic Acid/Carbon Nanotubes Antioxidant Hydrogel

Reactive oxygen species (ROS) level is closely associated with the physiological function of hematopoietic stem cells (HSCs) in ex vivo culture systems. Previously developed hydrogels in use of HSCs culture have generally failed in considering their antioxidant property. In the present work, antioxidant hydrogels are constructed to evaluate the biological effect of ROS on HSCs proliferation by suppressing oxidative stress damage. Functionalized carbon nanotubes (CNTs), which act as potential antioxidants, are physically encapsulated in biocompatible hyaluronic acid (HA) hydrogels to achieve long‐term antioxidant activity. Consequently, these hybrid hydrogels exhibit enhanced physical properties and superior scavenging capability on oxides and peroxides compared to the pure HA hydrogel. The results indicate that ROS significantly inhibit the biological characteristics of HSCs. Nevertheless, the proliferation ability and pluripotency are dramatically improved when the culture system is supplied with the antioxidant hydrogel, revealing that the CNT‐incorporated hydrogel can effectively relieve oxidative stress response in HSCs and reduce apoptosis from ROS. Therefore, the HA/CNT hydrogel can provide a novel strategy to establish an artificial microenvironment with a low ROS level for HSCs proliferation.     

Irradiated Ch/GG/PVP-based stimuli-responsive hydrogels for controlled drug release

Hydrogels based on gamma (γ) irradiated chitosan (pre-irradiated), guar gum, and polyvinyl pyrrolidone were crosslinked with various concentrations of (3-mercapto propyl)trimethoxysilane and fabricated by solution casting technique for the drug delivery applications. High molecular weight chitosan (Ch) possesses lower solubility and higher viscosity, these problems overcame by γ irradiation, which also generated hydrophilicity and effect of irradiated Ch on controlled drug release was assessed. FTIR analysis showed the development of chemical and physical interactions and confirmed the incorporation of characteristic peaks. SEM micrographs revealed porous structure of the prepared hydrogels. Swelling analysis of the hydrogels was performed in distilled water, buffer, and electrolyte mediums. All the hydrogel samples showed higher swelling at acidic pH and lower swelling at neutral and basic pH. These pH-responsive characteristics made these RCGP hydrogels an important contender for injectable controlled drug release. The ampicillin sodium drug was loaded and in vitro controlled release mechanism was evaluated in the PBS, SIF, and SGF which shown out of all prepared hydrogels (RCGP-1, RCGP-2, and RCGP-3), RCGP-1 has exhibited 87.4% release in PBS and 81.3% in SIF in 180 min.     

自组装多肽水凝胶支架中MSCs的三维培养及成骨分化

使用一种新型人工设计自组装多肽(RADA16)水凝胶作为三维培养支架评价MSCs成骨分化情况。将人骨髓MSCs培养增殖后接种到水凝胶中,在成骨分化培养液中进一步培养1～3周。荧光染色法观察细胞形态和存活情况;组织学染色检测MSCs ALP活性;半定量RT-PCR分析成骨特异性基因的表达。绝大多数MSCs在水凝胶支架内能够存活,呈纺锤样形态。诱导培养后蛋白和基因表达水平均检测到ALP活性,在14天时达到峰值。骨晚期分化特异性基因BSP也有表达,且表达量随培养时间延长而增多。自组装多肽水凝胶为MSCs的黏附生长及向成骨细胞分化提供良好的三维微环境,有望成为极具吸引力的骨组织工程支架材料。     

Nano-Sized Extracellular Matrix Particles Lead to Therapeutic Improvement for Cutaneous Wound and Hindlimb Ischemia

Cell-derived matrix (CDM) has proven its therapeutic potential and been utilized as a promising resource in tissue regeneration. In this study, we prepared a human fibroblast-derived matrix (FDM) by decellularization of in vitro cultured cells and transformed the FDM into a nano-sized suspended formulation (sFDM) using ultrasonication. The sFDM was then homogeneously mixed with Pluronic F127 and hyaluronic acid (HA), to effectively administer sFDM into target sites. Both sFDM and sFDM containing hydrogel (PH/sFDM) were characterized via immunofluorescence, sol–gel transition, rheological analysis, and biochemical factors array. We found that PH/sFDM hydrogel has biocompatible, mechanically stable, injectable properties and can be easily administered into the external and internal target regions. sFDM itself holds diverse bioactive molecules. Interestingly, sFDM-containing serum-free media helped maintain the metabolic activity of endothelial cells significantly better than those in serum-free condition. PH/sFDM also promoted vascular endothelial growth factor (VEGF) secretion from monocytes in vitro. Moreover, when we evaluated therapeutic effects of PH/sFDM via the murine full-thickness skin wound model, regenerative potential of PH/sFDM was supported by epidermal thickness, significantly more neovessel formation, and enhanced mature collagen deposition. The hindlimb ischemia model also found some therapeutic improvements, as assessed by accelerated blood reperfusion and substantially diminished necrosis and fibrosis in the gastrocnemius and tibialis muscles. Together, based on sFDM holding a strong therapeutic potential, our engineered hydrogel (PH/sFDM) should be a promising candidate in tissue engineering and regenerative medicine.