Injectable Self-Oxygenating Cardio-Protective and Tissue Adhesive Silk-Based Hydrogel for Alleviating Ischemia After Mi Injury.

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.

Application of 2,4,5-tris(2-pyridyl)imidazole as 'turn-off' fluorescence sensor for Cu(II) and Hg(II) ions and in vitro cell imaging.

The 2,4,5-tris(2-pyridyl)imidazole (L) molecule has been evaluated as a probe for dual sensing of Hg2+ and Cu2+ ions in EtOH/HEPES buffer medium (5 mM, pH = 7.34, 1:1, v/v). Probe L shows a good sensitive and selective turn-off response in the presence of both Hg2+ and Cu2+ ions, which is comprehensible under long UV light. The probe can detect Cu2+ ion in the pH range 3-11 and Hg2+ ion in pH 6-8. The limit of detection for Cu2+ (0.77 µM) is well under the allowable limit prescribed by the United States Environmental Protection Agency. Two metal (Cu2+ /Hg2+ ) ions are needed per L for complete fluorescence quenching. The probe shows marked reversibility on treatment with Na2 EDTA, making the protocol more economical for practical purposes. Paper strip coated with the L solution of EtOH can detect the presence of Cu2+ and Hg2+ ions in the sample using visible quenching of the fluorescence intensity. Density functional theory-time-dependent density functional theory (DFT-TDDFT) calculations support experimental observations, and d-orbitals of Cu2+ /Hg2+ provide a nonradiative decay pathway. Cell imaging study using HDF and MDA-MB-231 cells also supported the viability of L in detecting Cu2+ and Hg2+ ions in living cells.

A Heart-Breast Cancer-on-a-Chip Platform for Disease Modeling and Monitoring of Cardiotoxicity Induced by Cancer Chemotherapy.

Cardiotoxicity is one of the most serious side effects of cancer chemotherapy. Current approaches to monitoring of chemotherapy-induced cardiotoxicity (CIC) as well as model systems that develop in vivo or in vitro CIC platforms fail to notice early signs of CIC. Moreover, breast cancer (BC) patients with preexisting cardiac dysfunctions may lead to different incident levels of CIC. Here, a model is presented for investigating CIC where not only induced pluripotent stem cell (iPSC)-derived cardiac tissues are interacted with BC tissues on a dual-organ platform, but electrochemical immuno-aptasensors can also monitor cell-secreted multiple biomarkers. Fibrotic stages of iPSC-derived cardiac tissues are promoted with a supplement of transforming growth factor-ß 1 to assess the differential functionality in healthy and fibrotic cardiac tissues after treatment with doxorubicin (DOX). The production trend of biomarkers evaluated by using the immuno-aptasensors well-matches the outcomes from conventional enzyme-linked immunosorbent assay, demonstrating the accuracy of the authors' sensing platform with much higher sensitivity and lower detection limits for early monitoring of CIC and BC progression. Furthermore, the versatility of this platform is demonstrated by applying a nanoparticle-based DOX-delivery system. The proposed platform would potentially help allow early detection and prediction of CIC in individual patients in the future.

Synthesis of NNN Chiral Ruthenium Complexes and Their Cytotoxicity Studies.

The synthesis and characterization of chiral pincer-ruthenium complexes of the type (R2NNN)RuCl2 (PPh3) (R = 3-methylbutyl and 3,3-dimethylbutyl) is reported here. The cytotoxicity studies of these complexes were studied and compared with the corresponding activity of achiral complexes. The cytotoxic effect of pincer-ruthenium complexes on human dermal fibroblasts and human tongue carcinoma cells assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay displayed an inhibition of normal and cancer cell growth in a dose-dependent manner. Intracellular reactive oxygen species (ROS) level measurement, lactate dehydrogenase assay, DNA fragmentation, and necrosis studies revealed that treatment with pincer-ruthenium complexes induced a redox imbalance in SAS cells by upregulating ROS generation and caused necrotic cell death by disrupting the cellular membrane integrity.

Silk-based multilayered angle-ply annulus fibrosus construct to recapitulate form and function of the intervertebral disc.

Recapitulation of the form and function of complex tissue organization using appropriate biomaterials impacts success in tissue engineering endeavors. The annulus fibrosus (AF) represents a complex, multilamellar, hierarchical structure consisting of collagen, proteoglycans, and elastic fibers. To mimic the intricacy of AF anatomy, a silk protein-based multilayered, disc-like angle-ply construct was fabricated, consisting of concentric layers of lamellar sheets. Scanning electron microscopy and fluorescence image analysis revealed cross-aligned and lamellar characteristics of the construct, mimicking the native hierarchical architecture of the AF. Induction of secondary structure in the silk constructs was confirmed by infrared spectroscopy and X-ray diffraction. The constructs showed a compressive modulus of 499.18 ± 86.45 kPa. Constructs seeded with porcine AF cells and human mesenchymal stem cells (hMSCs) showed ∼2.2-fold and ∼1.7-fold increases in proliferation on day 14, respectively, compared with initial seeding. Biochemical analysis, histology, and immunohistochemistry results showed the deposition of AF-specific extracellular matrix (sulfated glycosaminoglycan and collagen type I), indicating a favorable environment for both cell types, which was further validated by the expression of AF tissue-specific genes. The constructs seeded with porcine AF cells showed ∼11-, ∼5.1-, and ∼6.7-fold increases in col Iα 1, sox 9, and aggrecan genes, respectively. The differentiation of hMSCs to AF-like tissue was evident from the enhanced expression of the AF-specific genes. Overall, the constructs supported cell proliferation, differentiation, and ECM deposition resulting in AF-like tissue features based on ECM deposition and morphology, indicating potential for future studies related to intervertebral disc replacement therapy.

Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium-on-a-Chip Application.

Bioprinting holds great promise towards engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, we have developed a novel and mechanically robust biomaterial-ink based on non-mulberry silk fibroin protein. The silk-based ink demonstrated suitable mechanical properties required in terms of elasticity and stiffness (~40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allowed the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which were able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin-43, and maintain synchronously beating of cardiomyocytes. The printed constructs were found to be non-immunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue-on-a-chip, the silk-based ink was used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC-CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. We confirmed the ability of silk-based supporting hydrogel towards maturation and viability of hiPSC-CSs and endothelial cells, and for applications in evaluating drug toxicity.

Glucose-methanol-based fed-batch fermentation for the production of recombinant human interferon gamma (rhIFN-γ) and evaluation of its antitumor potential.

Squamous cell carcinoma (SCC) is nonmelanoma skin cancer, which is very common in patients having T-cell immunosuppressant drugs. Anticancerous agents such as cytokines showed effective response on SCC. Human interferon-gamma (hIFN-γ), a type II cytokines, are having potent antiproliferative and immunomodulatory effects. In the current study, the fed-batch cultivation of recombinant Pichia pastoris was carried out, and its effect on cell biomass production, recombinant human interferon-gamma (rhIFN-γ) production, and the overflow metabolites was estimated. P. pastoris GS115 strain coexpressed with 6-phosphogluconolactonase (SOL3) and ribulose-phosphate 3-epimerase (RPE1) gene (GS115/rhIFN-γ/SR) resulted in 60 mg L-1 of rhIFN-γ production, which was twofold higher as compared with the production from GS115/rhIFN-γ strain. The antiproliferative potential of rhIFN-γ was examined on the human squamous carcinoma (A431) cell lines. Cells treated with 80 ng mL-1 of rhIFN-γ exhibited 50% growth inhibition by enhancing the production of intracellular reactive oxygen species levels and disrupting membrane integrity. Our findings highlight a state of art process development strategy for the high-level production of rhIFN-γ and its potential application as a therapeutic drug in SCC therapy.

3D Printed Cartilage-Like Tissue Constructs with Spatially Controlled Mechanical Properties.

Developing biomimetic cartilaginous tissues that support locomotion while maintaining chondrogenic behavior is a major challenge in the tissue engineering field. Specifically, while locomotive forces demand tissues with strong mechanical properties, chondrogenesis requires a soft microenvironment. To address this challenge, 3D cartilage-like tissue is bioprinted using two biomaterials with different mechanical properties: a hard biomaterial to reflect the macromechanical properties of native cartilage, and a soft biomaterial to create a chondrogenic microenvironment. To this end, a hard biomaterial (MPa order compressive modulus) composed of an interpenetrating polymer network (IPN) of polyethylene glycol (PEG) and alginate hydrogel is developed as an extracellular matrix (ECM) with self-healing properties, but low diffusive capacity. Within this bath supplemented with thrombin, fibrinogen containing human mesenchymal stem cell (hMSC) spheroids is bioprinted forming fibrin, as the soft biomaterial (kPa order compressive modulus) to simulate cartilage's pericellular matrix and allow a fast diffusion of nutrients. The bioprinted hMSC spheroids improve viability and chondrogenic-like behavior without adversely affecting the macromechanical properties of the tissue. Therefore, the ability to print locally soft and cell stimulating microenvironments inside of a mechanically robust hydrogel is demonstrated, thereby uncoupling the micro- and macromechanical properties of the 3D printed tissues such as cartilage.

The inhibitory effect of silk sericin against ultraviolet-induced melanogenesis and its potential use in cosmeceutics as an anti-hyperpigmentation compound.

Ultraviolet radiation (UVR)-induced redox imbalance in melanocytes triggers the activation of tyrosinase that results in melanogenesis and its related skin disorders. Supplementation of biological reductants or anti-tyrosinase compounds inhibits such melanogenesis. Silk sericin (SS), a globular protein, is known to possess antioxidant and anti-tyrosinase activities along with other biological attributes. However, its inhibitory activity against UVR-induced melanogenesis has yet to be explored. In the current study, we have scientifically explored the inhibitory activity of SS against UVR-induced melanogenesis. Anti-tyrosinase activity of SS was assessed using mushroom tyrosinase, showing that Antheraea assamensis sericin (AAS) and Philosamia ricini sericin (PRS) inhibited 50% of its activity. Inhibitory activity of SS against UVR-induced melanogenesis was assessed by measuring the cellular melanin content, intracellular tyrosinase activity, and reactive oxygen species (ROS) levels in mouse melanoma. SS pretreatment significantly reduced cellular melanin and ROS production in UV irradiated melanocytes compared with SS untreated cells. AAS treatment before UVA or UVB irradiation significantly inhibited tyrosinase activity. Rheological studies showed that the skin care formulation prepared by the addition of AAS to the basic formulation minimally affected its flow properties. Altogether, our results validate that AAS efficiently inhibited UVR-induced melanogenesis and it could be used as a potential antioxidant molecule in skin care cosmeceutics.

Inhibitory role of silk cocoon extract against elastase, hyaluronidase and UV radiation-induced matrix metalloproteinase expression in human dermal fibroblasts and keratinocytes.

Topical delivery of potent antioxidants maintain the redox balance of the skin, which leads to the downregulation of matrix metalloproteinase (MMP) expression and prevents UV radiation-induced photoaging. In this study, we aimed at investigating the inhibitory role of silk cocoon extract (SCE) isolated from the Antheraea assamensis (AA), Bombyx mori (BM), and Philosamia ricini (PR) silk varieties against UV radiation-induced MMP expression. Incubation of elastase and hyaluronidase with Antheraea assamensis silk cocoon extract (AASCE) caused 50% inhibition of activity. The assessment of total collagen content using the Sirius red assay showed that AASCE (10 µg mL-1) and Philosamia ricini silk cocoon extract (PRSCE at 100 µg mL-1 concentration) post-treatment significantly enhanced the total collagen content in UVA1 and UVB irradiated HDF cells, whereas BM silk cocoon extract (BMSCE at 100 µg mL-1 concentration) post-treatment significantly enhanced the total collagen content in UVA1-irradiated HDF cells. Gene expression studies revealed AASCE and PRSCE post-treatment downregulated the expression of interleukin (IL)-6, MMP-1 and upregulated procollagen genes in UV irradiated HDF cells. Gelatin zymography studies with AASCE post-treatment downregulated the release of MMP-2 and MMP-9 by HaCaT cells. The overall results validate AASCE efficiently shielding UV radiation-induced collagen and elastin degradation by downregulation of MMP expression, substantiating its further use as a potent antioxidant complement in skin care formulations.

Coordination-Driven Self-Assembly of Ionic Irregular Hexagonal Metallamacrocycles via an Organometallic Clip and Their Cytotoxicity Potency.

Two new irregular hexagons (6 and 7) were synthesized from a pyrazine motif containing an organometallic acceptor clip [bearing platinum(II) centers] and different neutral donor ligands (4,4'-bipyridine or pyrazine) using a coordination-driven self-assembly protocol. The two-dimensional supramolecules were characterized by multinuclear NMR, mass spectrometry, and elemental analyses. Additionally, one of the macrocycles (6) was characterized by single-crystal X-ray analyses. Macrocycles are unique examples of [2 + 2] self-assembled ensembles that are hexagonal but irregular in shape. These hexagon frameworks require the assembly of only four tectons/subunits. The cytotoxicity of platinum(II)-based macrocycles was studied using various cell lines such as A549 (human lung carcinoma), KB (human oral cancer), MCF7 (human breast cancer), and HaCaT (human skin keratinocyte) cell lines, and the results were compared with those of cisplatin. The smaller macrocycle (7) exhibited a higher cytotoxic effect against all cell types, and its sensitivity was found to be comparable with that of cisplatin for A549 and MCF7 cells. Cell cycle analysis and live propidium iodide staining suggest that the macrocycles 6 and 7 induced a loss of membrane integrity that ultimately might lead to necrotic cell death.

Aggregation induced enhanced and exclusively highly Stokes shifted emission from an excited state intramolecular proton transfer exhibiting molecule.

The inner filter effect due to self-quenching dominates the normal emission of dyes at higher concentrations, which would limit their applications. Since normal emission was also observed with aggregation induced emission enhancement (AIEE) active excited state intramolecular proton transfer (ESIPT) exhibiting molecules, two new molecules are synthesized and studied to obtain normal emission free AIEE. The molecules are 4-(3-(benzo[d]thiazol-2-yl)-5-tert-butyl-4-hydroxybenzyl)-2-(benzo[d]thiazol-2-yl)-6-tert-butyl phenol (bis-HPBT) and its oxazole analogue (bis-HPBO). Of these molecules, bis-HPBT, which is weakly fluorescent in tetrahydrofuran solution, shows a sudden high enhancement in fluorescence upon addition of 70% water due to the formation of aggregates. Though the normal emission is also observed in tetrahydrofuran, it is completely eliminated in the aggregates, and the aggregates display exclusive tautomer emission. However, bis-HPBO does not emit such an exclusive tautomer emission in the water/tetrahydrofuran mixture. The enhancement in the fluorescence quantum yield of bis-HPBT in 70% water is ∼300 times higher than that in tetrahydrofuran. The modulated molecular structure of bis-HPBT is the cause of this outstanding AIEE. The observation of almost exclusive tautomer emission is a new additional advantage of AIEE from bis-HPBT over other ESIPT molecules. Since the tautomer emission is highly Stokes shifted, no overlap with the absorption spectrum occurs and therefore, the inner filter effect is averted. The aggregated structure acts as a good fluorescence chemosensor for metal ions as well as anions. The aggregated structure is cell permeable and can be used for cell imaging.

Reloadable Silk-Hydrogel Hybrid Scaffolds for Sustained and Targeted Delivery of Molecules.

Tunable repeated drug administration is often inevitable in a number of pathological cases. Reloadable 3D matrices for sustained drug delivery are predicted as a prospective avenue to realize this objective. This study was directed toward sonication-induced fabrication of novel reloadable Bombyx mori silk fibroin (SF) (4, 6, and 8 wt %) hydrogel, injected within 3D porous (8 wt %) scaffolds. The focus was to develop a dual-barrier reloadable depot system for sustained molecular cargo release. Both the varying SF concentration (4, 6, and 8 wt %) and the sonication time (30, 45, and 60 s) dictated the extent of cross-linking, ß-sheet content, and porosity (1-10 µm) influencing the release behavior of model molecules. Release studies of model molecules (trypan blue, TB, 961 Da and bovine serum albumin, BSA, 66 kDa) for 28 days attested that the variations in their molecular weight, the matrix cross-linking density, and the scaffold-hydrogel interactions dictated the release behavior. The Ritger and Peppas equation was further fitted into the release behavior of model molecules from various SF matrices. The hybrid constructs exhibited high compressive strength along with in vitro compatibility using primary porcine chondrocytes and tunable enzymatic degradation as assessed for 28 days. The aptness of the constructs was evinced as a reloadable model molecule (BSA and fluorescein isothiocyanate-inulin, 3.9 kDa) depot system through UV-visible and fluorescence spectroscopic analyses. The novel affordable platform developed using silk scaffold-hydrogel hybrid constructs could serve as a sustained and reloadable drug depot system for administration of multiple and repeated drugs.

Aggregation induced enhanced emission of 2-(2'-hydroxyphenyl)benzimidazole.

In this study, the aggregation induced emission enhancement (AIEE) of 2-(2'-hydroxyphenyl)benzimidazole (HPBI) is reported. To investigate the AIEE process of HPBI, absorption/fluorescence spectroscopy, fluorescence imaging and field emission scanning electron microscopy were employed. A comparative study with 2-phenylbenzimidazole (PBI) divulges the significance of the hydroxyl group in the AIEE process. Further, molecular dynamics simulations have been carried out with explicit solvent molecules to follow the aggregation process of HPBI with time. The obtained molecular dynamics simulation results not only predicted the formation of aggregates but also provided detailed insight and information on the molecular interactions. The cellular studies showed aggregates yield higher fluorescence in the visible region inside HeLa cells in comparison to monomeric compounds which failed to exhibit any visible fluorescence inside the cell. The obtained aggregates were further found to be biocompatible and therefore can be used for bio-imaging applications.

Fabrication and Mechanical Characterization of Hydrogel Infused Network Silk Scaffolds.

Development and characterization of porous scaffolds for tissue engineering and regenerative medicine is of great importance. In recent times, silk scaffolds were developed and successfully tested in tissue engineering and drug release applications. We developed a novel composite scaffold by mechanical infusion of silk hydrogel matrix into a highly porous network silk scaffold. The mechanical behaviour of these scaffolds was thoroughly examined for their possible use in load bearing applications. Firstly, unconfined compression experiments show that the denser composite scaffolds displayed significant enhancement in the elastic modulus as compared to either of the components. This effect was examined and further explained with the help of foam mechanics principles. Secondly, results from confined compression experiments that resemble loading of cartilage in confinement, showed nonlinear material responses for all scaffolds. Finally, the confined creep experiments were performed to calculate the hydraulic permeability of the scaffolds using soil mechanics principles. Our results show that composite scaffolds with some modifications can be a potential candidate for use of cartilage like applications. We hope such approaches help in developing novel scaffolds for tissue engineering by providing an understanding of the mechanics and can further be used to develop graded scaffolds by targeted infusion in specific regions.

High-strength silk protein scaffolds for bone repair.

Biomaterials for bone tissue regeneration represent a major focus of orthopedic research. However, only a handful of polymeric biomaterials are utilized today because of their failure to address critical issues like compressive strength for load-bearing bone grafts. In this study development of a high compressive strength (~13 MPa hydrated state) polymeric bone composite materials is reported, based on silk protein-protein interfacial bonding. Micron-sized silk fibers (10-600 µm) obtained utilizing alkali hydrolysis were used as reinforcement in a compact fiber composite with tunable compressive strength, surface roughness, and porosity based on the fiber length included. A combination of surface roughness, porosity, and scaffold stiffness favored human bone marrow-derived mesenchymal stem cell differentiation toward bone-like tissue in vitro based on biochemical and gene expression for bone markers. Further, minimal in vivo immunomodulatory responses suggested compatibility of the fabricated silk-fiber-reinforced composite matrices for bone engineering applications.

Current advances in engineering meniscal tissues: insights into 3D printing, injectable hydrogels and physical stimulation based strategies.

The knee meniscus is the cushioning fibro-cartilage tissue present in between the femoral condyles and tibial plateau of the knee joint. It is largely avascular in nature and suffers from a wide range of tears and injuries caused by accidents, trauma, active lifestyle of the populace and old age of individuals. Healing of the meniscus is especially difficult due to its avascularity and hence requires invasive arthroscopic approaches such as surgical resection, suturing or implantation. Though various tissue engineering approaches are proposed for the treatment of meniscus tears, three-dimensional (3D) printing/bioprinting, injectable hydrogels and physical stimulation involving modalities are gaining forefront in the past decade. A plethora of new printing approaches such as direct light photopolymerization and volumetric printing, injectable biomaterials loaded with growth factors and physical stimulation such as low-intensity ultrasound approaches are being added to the treatment portfolio along with the contemporary tear mitigation measures. This review discusses on the necessary design considerations, approaches for 3D modeling and design practices for meniscal tear treatments within the scope of tissue engineering and regeneration. Also, the suitable materials, cell sources, growth factors, fixation and lubrication strategies, mechanical stimulation approaches, 3D printing strategies and injectable hydrogels for meniscal tear management have been elaborated. We have also summarized potential technologies and the potential framework that could be the herald of the future of meniscus tissue engineering and repair approaches.

3D Bioprinted Human Skin Model Recapitulating Native-Like Tissue Maturation and Immunocompetence as an Advanced Platform for Skin Sensitization Assessment.

Physiologically-relevant in vitro skin models hold the utmost importance for efficacy assessments of pharmaceutical and cosmeceutical formulations, offering valuable alternatives to animal testing. Here, an advanced immunocompetent 3D bioprinted human skin model is presented to assess skin sensitization. Initially, a photopolymerizable bioink is formulated using silk fibroin methacrylate, gelatin methacrylate, and photoactivated human platelet releasate. The developed bioink shows desirable physicochemical and rheological attributes for microextrusion bioprinting. The tunable physical and mechanical properties of bioink are modulated through variable photocuring time for optimization. Thereafter, the bioink is utilized to 3D bioprint "sandwich type" skin construct where an artificial basement membrane supports a biomimetic epidermal layer on one side and a printed pre-vascularized dermal layer on the other side within a transwell system. The printed construct is further cultured in the air-liquid interface for maturation. Immunofluorescence staining demonstrated a differentiated keratinocyte layer and dermal extracellular matrix (ECM)-remodeling by fibroblasts and endothelial cells. The biochemical estimations and gene-expression analysis validate the maturation of the printed model. The incorporation of macrophages further enhances the physiological relevance of the model. This model effectively classifies skin irritative and non-irritative substances, thus establishing itself as a suitable pre-clinical screening platform for sensitization tests.

Secondary Chemical Cross-Linking to Improve Mechanical Properties in a Multifaceted Biocompatible Strain Sensor.

A new conductive and transparent organohydrogel is developed with high stretchability, excellent mechanical, self-healing, antifreezing, and adhesive properties. A simple one-pot polymerization method is used to create polyacrylamide cross-linked through N,N'-methylenebis(acrylamide) (MBAA) and divinylbenzene (DVB). The dual chemical cross-linked gel network is complemented by several physical cross-links via hydrogen bonding and π-π interaction. Multiple chemical and physical cross-links are used to construct the gel network that allows toughness (171 kPa), low modulus (≈45 kPa), excellent stretchability (>1100%), and self-healing ability. The use of appropriate proportions of the water/glycerol binary solvent system ensures efficient environment tolerance (-20 to 40 °C). Phytic acid is used as a conductive filler that provides excellent conductivity and contributes to the physical cross-linking. Dopamine is incorporated in the gel matrix, which endows excellent adhesive property of the gel. The organohydrogel-based strain sensors are developed with state-independent properties, highly linear dependence, and excellent antifatigue performance (>100 cycles). Moreover, during the practical wearable sensing tests, human motions can be detected, including speaking, smiling, and joint movement. Additionally, the sensor is biocompatible, indicating the potential applications for the next generation of epidermal sensors.

Omentum Extracellular Matrix-Silk Fibroin Hydroscaffold Promotes Wound Healing through Vascularization and Tissue Remodeling in the Diabetic Rat Model.

Nonhealing diabetic wounds are often associated with significant mortality and cause economic and clinical burdens to the healthcare system. Herein, a biomimetic hydroscaffold is developed using omentum tissue-derived decellularized-extracellular matrix (dECM) and silk fibroin (SF) proteins that associate the behavior of a collagenous fibrous scaffold and a hydrogel to reproduce all aspects of the provisional skin tissue matrix. The chemical cross-linker-free in situ gelation property of the two types of SF proteins from Bombyx mori and Antheraea assamensis ensures the adherence of dECM with surrounding tissue on the wound bed, circumventing further suturing. The physicochemical and mechanical properties of the composite hydroscaffold (SF-dECM) were thoroughly evaluated. The hydroscaffolds were found to support the growth and proliferation of human dermal fibroblasts and influence the angiogenic potential of endothelial cells under in vitro conditions. Furthermore, the healing efficacy of the composites was evaluated by generating full-thickness wounds on a streptozotocin-induced diabetic rat model. The presence of dECM components in the composite facilitated the rate of wound closure, granulation tissue formation, and re-epithelialization by providing intrinsic cues to advance the inflammatory stage and stimulating angiogenesis. Collectively, as an off-the-shelf wound dressing requiring only a single topical administration, the SF-dECM hydroscaffold is a promising, cost-effective dressing for the management of chronic diabetic wounds.