Hydrogel Group Research Articles

Applications of a biocompatible alginate/pericardial fluid-based hydrogel for the production of a bioink in tissue engineering.

Enhancing the biocompatibility of biomaterials is a critical aspect of tissue engineering and regenerative medicine. Advances in 3D bioprinting technology, blending natural and synthetic materials for the production of bioink, offer new opportunities to develop highly biocompatible materials that can closely mimic the native tissue environment. In this study, we used pericardial fluid structure (PFS)-based material together with alginate to mimic the extracellular matrix (ECM) and produce a bioink material. Thus, blended alginate with PFS material and MC3T3-E1 pre-osteoblast cell-laden hydrogels characterized by comparing each other, especially alginate hydrogels, and evaluated in terms of biocompatibility for tissue engineering applications. According to the rheological analysis results, all hydrogel groups A, A-PFS (150mg), and A-PFS (1:1) had viscoelastic properties. Mechanical tests showed that the A-PFS (1:1) hydrogel had the most strength properties. Additionally, the viscosity values of the hydrogel solutions were in an applicable range for use in 3D bioprinters. It was also found out that PFS increased the biocompatibility of alginate-based bioink, in terms of cell proliferation and differentiation. Overall, these findings suggest that alginate and pericardial fluid-based materials can be successfully used for bioink production. The resulting hydrogels exhibit viscoelastic properties, appropriate viscosity for 3D bioprinting, and support cell viability, proliferation, and osteogenic differentiation. This research has the potential not only to produce bioink but also to produce injectable hydrogels and drug delivery systems, which can become biocompatible materials that can be used for tissue engineering and regenerative medicine applications.

“Young-Mechanical Niche” biomimetic hydrogel promotes dental pulp regeneration through YAP-dependent mechanotransduction

Aging leads to the irreversible deterioration of the extracellular matrix (ECM), compromising cell self-renewal, differentiation, and tissue regeneration. However, the specific mechanisms by which age-related changes in ECM-mediated cell mechanical microenvironment impair regeneration remain elusive. Human dental pulps (hDPs) provide an ideal model to explore this issue due to their accessibility and distinct mechanical properties. In this study, we discovered that young hDPs exhibit higher stiffness and viscoelasticity (i.e., faster stress relaxation time) compared to aged hDPs. Leveraging these findings, we engineered three groups of biomimetic hydrogels recapitulating the native mechanical microenvironment of young and aged hDPs. Our results demonstrated that Y-Gel, which replicates the high stiffness and viscoelasticity of young hDPs, significantly enhances the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs) in vitro and promotes dental pulp regeneration in vivo more effectively than hydrogels mimicking either aged stiffness (AS-Gel) or aged viscoelasticity (AV-Gel) alone. Moreover, YAP-dependent mechanotransduction, particularly through the YAP/TEAD1/CTGF/Cyr61 signaling pathway, plays a critical role in mediating these regenerative effects, with stiffness emerging as a more dominant factor than viscoelasticity. This study provides new insights into the synergistic role of mechanical factors in regulating cell behavior and offers a promising strategy for optimizing mechanical microenvironment to enhance dental pulp regeneration and potentially other tissue regeneration applications, especially from the mechanomedicine perspective.

APullulan polysaccharide-based flame-retardant polyelectrolyte hydrogel for high-safety flexible zinc ion capacitors

Potential safety hazards such as leakage, flammability and thermal runaway of liquid electrolytes in conventional energy storage devices have seriously hindered their further development. In this work, a flame-retardant polyacrylamide/pullulan/phytic acid (PAM/PUL/PA) hydrogel electrolyte is prepared by using PA as flame-retardant additive, PAM as main polymer chain by one-step radical polymerization method. The PAM/PUL/PA hydrogel shows good flame-retardant properties with limiting oxygen index of up to 58 %, high mechanical performance with stretch up to 1535 % and 92 kPa tensile stress. Zinc ion capacitor (ZIC) assembled with the PAM/PUL/PA hydrogel as electrolyte and separator exhibits high ionic conductivity of 22.54 mS cm−1, high specific capacity of 111.5 mAh g−1 at 0.1 A g−1 and energy density of 97.57 Wh kg−1 at a power density of 49.99 W kg−1, as well as good capacitance retention of 74.6 % even after 10,000 cycles. Furthermore, the ZIC has outstanding flexibility, the capacitance retention rate almost unchanged even after 1000 consecutive bending of deformations. These excellent properties are attributed to the hydrogen bonds easily formed by polar functional groups in hydrogels and the electrostatic interactions with metal ions. This work presented a simple and general pathway to prepare high-safety flexible energy storage devices with multifunctional properties.

Dental pulp stem cell‑derived extracellular vesicles loaded with hydrogels promote osteogenesis in rats with alveolar bone defects.

Alveolar bone defects caused by inflammation, trauma and tumors adversely affect periodontal health, causing tooth loosening or dentition defects, thus affecting denture or implant repair. Advancements in tissue engineering technology and stem cell biology have significantly improved the regenerative reconstruction of alveolar bone defects. The multiple trophic activities of extracellular vesicles (EVs) produced by mesenchymal stem cells play important roles in exerting their therapeutic effects. Several studies have reported the role of dental pulp stem cells (DPSCs) in bone regeneration, but the regenerative effects of DPSC‑EVs on alveolar bone defects are unclear. In the present study, the osteogenic effects of DPSC‑EVs on Hertwig's epithelial root sheath (HERS) cells in vitro and their osteoinductive effects in an alveolar bone defect rat model were investigated. The results showed that DPSC‑EVs significantly promoted the expression of osteogenic genes, such as runt‑related transcription factor 2 and alkaline phosphatase, and increased the osteogenic differentiation capability of HERS. These findings suggested that transforming growth factor β1 inhibition decreased DPSC‑EV‑induced Smad, MAPK and ERK phosphorylation in HERS. In vivo, DPSC‑EV‑loaded hydrogels were transplanted into the alveolar sockets of Sprague‑Dawley rats and observed for eight weeks. The new bone grew concentrically in the DPSC‑EV or DPSC‑EV‑loaded hydrogel group, with greater bone mass than that in the control group, and the bone volume/total volume increased notably. The results confirmed the osteogenic and osteoinductive effects of DPSC‑EVs and DPSC‑Exo‑loaded hydrogels on alveolar bone defects. Due to their low immunogenicity, high stability, good biocompatibility and osteogenic propensity, DPSC‑EV‑loaded hydrogels are a safe cell‑free therapeutic approach for defective alveolar bone regeneration.

Exosomes derived from Umbilical cord mesenchymal stem cell promote hair regrowth in C57BL6 mice through upregulation of the RAS/ERK signaling pathway.

Androgenetic alopecia is one of the common types of hair loss and has become a medical and social problem due to its increasingly young onset. Existing therapies, although effective, have serious side effects and therefore better treatments need to be sought. The aim of this study was to evaluate the efficacy of umbilical cord mesenchymal stem cell-derived exosomes in the treatment of androgenetic alopecia and to investigate the mechanism of exosome regulation of hair growth. First, we randomly divided 20 C57BL/6J mice into blank group, model group, positive control group and exosomal hydrogel group, and mice were treated with hair removal on the back. The mice were injected intraperitoneally with dihydrotestosterone solution except for the blank group. At the end of the experiment, new hairs were collected and the differences in length, diameter and number of hair follicles were compared among the groups; the histopathological changes of hair follicles were observed by HE staining; the expression of androgen receptor mRNA and protein in skin tissues were compared; and the skin tissues were analyzed by real-time PCR, western blotting, immunofluorescence staining and transcriptome sequencing. Finally, the results of transcriptome sequencing experiments were verified by real-time PCR, western blotting and other techniques for the corresponding genes and proteins. Compared with the blank group, mice in the model group had shorter hair length and reduced hair diameter, and pathological observation showed that the total number of hair follicles was significantly reduced and the hair follicles were miniaturized; compared with the model group, mice in the positive control and exosome groups had longer hair length, larger hair diameter and more hair follicles; the androgen receptor mRNA content and protein expression in the skin tissue of mice in the model group were significantly higher than those in the blank group, and the protein expression in the exosome gel group was lower than that in the model group. Similarly, compared with the model group, the expression of stemness-related proteins K15 and CD200 in the skin tissues of mice in the exosome group increased, and the expression of PCNA, a protein related to cell proliferation, increased. The KEGG data showed that the differential genes were mainly enriched in the RAS/ERK pathway. In this study, we demonstrated the therapeutic effect of umbilical cord MSC-derived exosomes on androgenetic alopecia and verified that exosomes regulate hair follicle stem cell stemness through the RAS/ERK pathway to promote hair proliferation and thus hair growth in mice with androgenetic alopecia, providing a potential therapeutic strategy for androgenetic alopecia.

Injectable alginate chitosan hydrogel as a promising bioengineered therapy for acute spinal cord injury

Dealing with spinal cord injuries presents problematic due to multiple secondary mechanisms. Beyond primary concerns like paralysis and disability, complications including urinary, gastrointestinal, cardiac, and respiratory disorders, along with substantial economic burdens may occur. Limited research focuses on modeling and treating contusion and compression injuries. Tissue engineering emerges as an innovative treatment, targeting lesion pathophysiology. This study was evaluated implanting injectable biomaterials into injury-induced cavity before glial scar formation, avoiding tissue incisions and minimizing further damage. The efficacy of injectable alginate/thiolated chitosan hydrogel was investigated for acute spinal cord injury induced by Vanický method in Wistar rats. Three days post-injury, hydrogel was administrated through microinjection after laminectomy. After 60 days, the hydrogel group demonstrated notable motor function enhancement compared to the control by the BBB locomotor test (P < 0.05). However, no statistically significant differences were observed in MRI assessment concerning lesion severity. Stereological and histopathological evaluations revealed a reduction in vacuole volume and the presence of axon profiles within the scaffold (P < 0.05), alongside reduced infiltration of inflammatory and Gitter cells in the hydrogel group, although the latter was not statistically significant compared to the control. Thiolated chitosan/ alginate hydrogel implantation may be regarded as a promising treatment to enhance motor function by restraining destructive processes post-acute spinal cord injury.

Modifying functional groups of straw-based hydrogel provide soil N2O mitigation potential by complete denitrification

Farmed soil is considered to contribute more than 60% anthropogenic N2O emission which plays critical role in global warming potential. Straw-based hydrogels with abundant functional groups are commonly used in environmental and agronomic applications primarily as adsorbents. Those functional groups could mediate electron transfer in the process of adsorbates and might also regulate N2O emission. However, it was still unclear whether and how these functional groups affect the process. To address this knowledge gap, we employed spectral analysis and a robotized incubation system to determine mechanisms of different functional groups in influencing soil N2O. The results indicated that the straw-based hydrogel was capable of significantly reducing the emission of N2O in denitrification, and the electrochemical properties of the hydrogel had promoting effect of the microbial genetic potential for N2O reduction. Specifically, carboxymethyl (R-COO) and primary amine groups (R-NH2) promoted complete denitrification through electron supply. Furthermore, R-NH2 had a significant negative correlation with N2O emissions. To further verify the role of specific structures and functional groups in denitrification, we conducted an experiment using pure lignin as a template. This experiment resulted in an increase in R-NH2 content to 13.2% and a decrease in N2O emissions by 49.1% compared with straw hydrogel. These results prove the feasibility of straw-based hydrogel as a redox system to accelerate complete denitrification, and the electron-donating functional groups were significantly related to the reduction rate of N2O. Finally, based on these mechanisms, functional group targeted grafting technology was proposed to improve its ability to mitigate N2O emission reduction.

Hydrogel encapsulating gold nanoparticles for targeted delivery of nitroglycerin to reduce post-cardiac dysfunction inflammation by inhibiting the Wnt/β-catenin signaling pathway.

The discovery of nitric oxide's role in biological processes like platelet function, vasodilation, cell permeability, and inflammation has advanced our understanding of organic nitrate therapy's hemodynamic and nonhemodynamic effects. Short-term use of organic nitrates prevents left ventricular enlargement and infarct expansion. However, information on their long-term impact on LV remodeling in post-acute cardiac dysfunction patients is limited. In this study, we utilized an innovative active hydrogel with gelatin (Gel)/polyethylene glycol (PEG)/polylactic acid (PLA) encapsulating gold nanoparticles (AuNPs)-based drug delivery system for the sustained release of nitroglycerin (NTG). Gel/PEG/PLA/NTG/AuNPs hydrogel-based system is a non-transplant surgical method that can adhere to the surface of the heart and deliver the drug directly to the epicardium. Cardiac dysfunction was induced by ligating the left anterior descending coronary artery. Echocardiograms were used to study the pre- and post-operative hemodynamics. Hematoxylin and eosin (H&E) and Masson's trichrome stain (MTS) stainingrevealed that the acute myocardial infarction (AMI) rats' group had irregularly shaped fibers and a lack of transverse striations, whereas Gel/PEG/PLA/NTG/AuNPs hydrogel group showed significant improvement. Rats in the Gel/PEG/PLA hydrogel group demonstrated marked vasodilation, compared to the AMI group. Mechanistically, we determined that hydrogel disrupts the initiation of post-cardiac dysfunction via inhibiting Wnt/β-catenin transcriptional activation. Hence, the Gel/PEG/PLA/NTG/AuNPs hydrogel group effectively protected against ischemic injury and inflammation in AMI, demonstrating a novel method for treating acute cardiac dysfunction.

Activity of SNEDDS Hydrogel Ethyl Acetate Fraction of Kadara Dompu (Caesalpinia bonduc) Seed Extract on Blood Sugar Levels and Wounds Healing in Diabetic Rats Model Based on Collagen Tissue Distribution Histo Pathological Observations

High blood glucose levels can cause fatal complications, one of which is gangrene. Gangrene is a chronic condition and very difficult to cure. The final solution that will be carried out is amputation so as not to cause a more serious condition. Treatment for diabetic gangrene in general is by administering broad spectrum antibiotics. The use of antibiotics is starting to experience resistance, so alternatives to traditional drug therapy are being developed to suppress the occurrence of resistance. The results of the phytochemical screening of the ethyl acetate fraction of the Kadara seeds contained both hydrophilic and lipophilic saponin and flavonoid compounds. Flavonoids function as anti-fungal, anti-septic and cell regeneration or repair, while saponins can stimulate collagen growth and stimulate the growth of new cells. This research is a development of previous research on the effectiveness of the SNEDDS formula for Ethylacetate Fraction of Kadara Fruit Seed Flesh Extract against S.epidermidis and E.coli bacteria that cause diabetic gangrene in vitro. To facilitate the delivery of SNEDDS preparations, a topical preparation formulation is needed, one of which is Hydrogel. This study aims to determine the effect of administering SNEDDS hydrogel ethyl acetate fraction of Kadara fruit seed extract on blood sugar levels and the extent of wound healing in diabetic rats based on the distribution of collagen tissue through histopathological observations. This research began with maceration to obtain a thick extract, followed by fractionation and making SNEDDS hydrogel preparations. Evaluation of preparations and activity tests is carried out. Research results show that the SNEDDS hydrogel fraction of ethyl acetate fruit seed extract can reduce blood sugar on day 10 but is still in the hyperglycemic category from 487 mg/dL to 286 mg/dL. The density of collagen connective tissue formed by SNEDDS hydrogel from the ethyl acetate fraction was the highest (57.07%), with positive control (41.28%) and negative control (17.93%). Statistical data shows that the positive control group is significantly different from the negative control with a value of p= 0.025&lt;0.05 and the positive control group is not significantly different from the SNEDDS hydrogel fraction ethyl acetate group with a value of p=0.166&gt;0.05. Meanwhile, the SNEDDS hydrogel group with the ethyl acetate fraction was significantly different from the negative group, p value = 0.003 &lt;0.005.

Chitosan/Fibroin Biopolymer-Based Hydrogels for Potential Angiogenesis in Developing Chicks and Accelerated Wound Healing in Mice.

Potential therapies for wound management remain one of the most challenging affairs to date. Biopolymer hydrogels possess inherent properties that facilitate the healing of damaged tissue by creating a supportive and hydrated environment. Chitosan/fibroin hydrogels were formulated with poly (vinyl pyrrolidone) and cross-linked using 3-aminopropyl (diethoxy) methylsilane (APDEMS) for the aforementioned function. The hydrogels were characterized through Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy, and their swelling response was observed using a variety of solvents. Additionally, hydrogels were investigated for biomedical applications. As the amount of fibroin added to the hydrogels increased, the swelling ratio decreased. The analysis of chorioallantoic membrane (CAM) assay revealed that higher concentrations of fibroin in the hydrogel were directly correlated with increased angiogenesis. The intragroup comparison showed that the vascular number in the CPF5 group was significantly increased (p ≤ 0.05) compared to other hydrogel groups. The wound healing efficiency of the prepared hydrogels showed that the rate of wound reduction (99.06%) was remarkably (p ≤ 0.05) high in the hydrogel group with a greater fibroin content against control (67.03%). Histological findings of wounded tissues corroborate the abovementioned results, showing dense fibrous connective tissues in the fibroin group compared to the control. The results of this work provide thorough preclinical evidence that chitosan-fibroin biopolymers are involved in enhanced angiogenesis in growing chicks and speed up wound healing in mice without any obvious toxicity.

Evaluation of a Kenaf Nanocrystalline Cellulose-based Hydrogel Containing Platelet Lysate for Full-thickness Wound Healing

Introduction: Healing full-thickness wounds is often challenging and time-consuming, with complications such as scarring and infections. The standard treatment, split skin grafting, has limitations due to the availability of healthy donors and suitability for immunocompromised patients. Method: Autologous platelet lysate (PL) has been popular for tissue regenerative potential because it contains growth factors (GF) and is a safer option for bedridden patients with weak immune systems. However, PL has inconsistent clinical efficacy, high costs, and a short half-life. To address these issues, this study explores a novel delivery system by fabricating a chitosan/nanocrystalline cellulose (CS/NCC) hydrogel to sustainably deliver autologous PL to the wound site. Notably, NCC was prepared from kenaf bast fibers using acid hydrolysis and integrated into the CS matrix through physical entrapment without any chemical crosslinkers. The composite hydrogel was then enriched with autologous PL and further characterized for its physicochemical properties, in vitro GF release, and compatibility with skin cells. At the molecular level, gene expression of wound healing genes was facilitated using qPCR, revealing that the PL-supplemented hydrogel upregulated the expression of extracellular matrix genes. An in vivo study using a full-thickness wound model demonstrated that the CS-NCC-PL hydrogel dressing achieved 81.8% wound closure within 14 days, compared to the control groups. Result: Histological analysis indicated enhanced re-epithelialization, angiogenesis, and collagen deposition. Particularly, the CS-NCC-PL hydrogel group showed a significantly higher hydroxyproline content (60.62 ± 11.46 μg/100 mg) by day 14. Immunohistochemistry results revealed elevated levels of α-SMA and CD31, markers of myofibroblast presence and angiogenesis, peaking at day 7. Conclusion: These findings suggest that the CS-NCC-PL hydrogel is a promising personalized wound dressing for bedridden patients, offering improved healing outcomes in hospital settings.

Protective effect of carvacrol hydrogel on the alveolar bone in rats with periodontitis.

This study aimed to investigate the protective effect and mechanism of carvacrol hydrogel on the alveolar bone in rats with periodontitis. A thermosensitive hydrogel supported by carvacrol was prepared using poloxamer and hydroxypropyl methyl cellulose as matrix. SD rats were randomly divided into blank group, periodontitis group, blank hydrogel group, and low-, medium-, and high-dose hydrogel groups. The periodontitis symptoms and the CT structure of the alveolar bone were observed. The changes in liver, spleen, kidney, and periodontal tissues were observed. The related indexes of bone metabolism in serum were detected. The expression of osteoprotegerin (OPG) and nuclear transcription factor-κB (NF-κB) pathway proteins was determined by Western blot. The levels of inflammatory factors were assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Carvacrol hydrogel had good slow release, biocompatibility, and cell adhesion. The periodontitis of rats in the carvacrol hydrogel group was significantly alleviated, the expression of OPG protein in gingival tissue was significantly increased (P<0.01), and the levels of receptor activator of NF-κB ligand (RANKL), receptor activator of NF-κB (RANK), NF-κB protein, and inflammatory factors were significantly decreased (P<0.01). Carvacrol hydrogel can regulate the OPG and NF-κB pathways, reduce alveolar bone absorption, and improve periodontal inflammation.

Drug-Loaded Mesoporous Polydopamine Nanoparticles in Chitosan Hydrogels Enable Myocardial Infarction Repair through ROS Scavenging and Inhibition of Apoptosis.

In this study, we synthesized mesoporous polydopamine nanoparticles (MPDA NPs) using an emulsion-induced interface assembly strategy and loaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic attraction to form EGCG@MPDA NPs. In the post myocardial infarction (MI) environment, these interventions specifically aimed to eliminate reactive oxygen species (ROS) and facilitate the repair of MI. We further combined them with a thermosensitive chitosan (CS) hydrogel to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel). Utilizing in vitro experiments, the EGCG@MPDA/CS hydrogel exhibited excellent ROS-scavenging ability of H9C2 cells under the oxidative stress environment and also could inhibit their apoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular ejection fraction (LVEF) in infarcted rat models post injection for 28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ± 0.78%, P < 0.05). In comparison to the PBS group, histological analysis revealed a substantial increase in left ventricular (LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58 ± 0.03 to 1.39 ± 1.11 mm, P < 0.05). This work presents a novel approach to enhance MI repair by employing the EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local oxidative stress by ROS and stimulates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.

PH-RESPONSIVE INTERPENETRATING POLYMER NETWORK HYDROGEL MICROBEADS OF POLYACRYLAMIDE-G-GUM KONDAGOGU AND SODIUM ALGINATE FOR GASTROPROTECTIVE DRUG DELIVERY: IN VITRO-IN VIVO CHARACTERIZATIONS

The present work aims to design interpenetrating polymer network (IPN) mediated hydrogel microbeads of hydrolyzed polyacrylamide-g-gum kondagogu (H-pAAm-g-GK) and sodium alginate (SA) for pH-sensitive gastroprotective drug delivery of diclofenac sodium (DS). In brief, the pAAm-g-GK was prepared using microwave irradiation, followed by conversion into a pH-sensitive polymer (H-pAAm-g-GK) using alkaline hydrolysis. Then, DS-loaded IPN microbeads were made utilizing an ionotropic gelation method using Ca+2 ions and glutaraldehyde (GA) as a crosslinking agent. After this, different characterizations, such as FT-IR, DSC, PXRD, swelling analysis, drug entrapment, drug release study, in vivo anti-inflammatory activity, etc., were performed. The amorphous state of DS in the microbeads was validated by thermograms and diffractograms, whereas SEM analysis confirmed the spherical shape of the obtained DS-loaded H-pAAm-g-GK@SA mediated microbeads. The pulsatile swelling analysis assured the H-pAAm-g-GK@SA mediated microbeads showed significantly increased swelling as the pH switched from 1.2 to 7.4. Additionally, the microbeads exhibit a 15% DS release in a pH 1.2 buffer medium, while a substantial 94% of the drug was released in a pH 7.4 buffer. It assured the DS release was drastically augmented as the pH of the surrounding medium was switched from acidic to alkaline. Principally, the COOH- groups of hydrogels offer ionization at higher pH levels, wherein the osmotic pressure within the microbeads rises, resulting in more swelling and higher drug release. Finally, the in vivo anti-inflammatory activity assured pH-sensitive sustained release of DS. In conclusion, the H-pAAm-g-GK@SA mediated pH-sensitive IPN hydrogel microbeads show potential in the design of gastroprotective oral delivery systems for DS. In the future, H-pAAm-g-GK can be used for the design of pH-sensitive IPN hydrogel microbeads for targeted delivery.

Thermosensitive and injectable chitosan-based hydrogel embedding umbilical cord mesenchymal stem cells for β-cell repairing in type 2 diabetes mellitus

A thermosensitive and injectable hydrogel composed of chitosan (CS), chitosan biguanide hydrochloride (CSG) and collagen (CO) could embed umbilical cord mesenchymal stem cells (UC-MSCs), then was applied for the type 2 diabetes mellitus (T2DM) treatment in vivo. UC-MSCs could adhere well on CS/CSG/CO hydrogel surface and cell division could be clearly observed. Especially, UC-MSCs maintained alive till they grew in CS/CSG/CO hydrogel for 8 days, while the amount of UC-MSCs was limited due to the steric hindrance in hydrogel. To T2DM mice contrastive treatment by intraperitoneal injection for thirteen weeks, UC-MSCs + Hydrogel group could improve the impaired glucose tolerance, maintain glucose homeostasis in vivo, and restore islet morphology for T2DM mice. The immunofluorescence staining and western blot experiments further displayed that both the nuclear antigen Ki67 for cell proliferation and pancreatic duodenal homeobox-1 (Pdx1) expression in UC-MSCs + Hydrogel group were significantly higher than the expressions in untreated T2DM group and treated UC-MSCs + PBS group, which indicated that UC-MSCs + Hydrogel elevated β cell transcriptional activity. Moreover, the positivity rates of iNOS and CD163 in UC-MSCs + Hydrogel group were generally decreased and increased, respectively, compared to those in untreated T2DM group and treated UC-MSCs + PBS group. It displayed that UC-MSCs + Hydrogel could reduce M1 macrophage expression and increase M2 macrophage polarization in T2DM mice.

Near-Infrared Stimuli-Responsive Hydrogel Promotes Cell Migration for Accelerated Diabetic Wound Healing.

Diabetic wound healing including diabetic foot ulcers is a major clinical challenge, which could bring an increased level of mortality and morbidity. However, conventional wound dressings exhibit limited healing efficacy due to their lack of active modulation for the healing process. Here, a near-infrared (NIR) stimuli-responsive composite hydrogel dressing with the synergistic effect of both mechanical contraction and epithelial-mesenchymal transition (EMT) was developed to facilitate cell migration and vascularization for diabetic wound healing. In the methacrylated gelatin-based composite hydrogel, N-isopropylacrylamide and polydopamine nanoparticles were incorporated to endow the composite hydrogel with thermosensitive and photothermal properties. Linagliptin (LIN) was loaded into the composite hydrogel, and the drug release rate could be controlled by NIR laser irradiation. NIR-triggered on-demand active contraction of wound area and LIN release for biological stimulation were potentially realized in this responsive system due to the thermally induced sol-gel transition of the composite hydrogel. The release of loaded LIN could effectively promote cell migration by activating EMT and enhancing angiogenesis. In the full-thickness skin defect model, the LIN-loaded composite hydrogel with NIR laser irradiation had the highest wound closure rate as compared with the pure hydrogel and LIN-loaded hydrogel groups. Therefore, this composite hydrogel can serve as an excellent platform for promoting wound healing and will find more practical value in clinical treatment.

Injectable Tannin-Containing Hydroxypropyl Chitin Hydrogel as Novel Bioactive Pulp Capping Material Accelerates Repair of Inflamed Dental Pulp.

Conventional pulp capping materials have limited anti-inflammatory capacity. It is necessary to develop more effective pulp capping material for the treatment of inflamed pulps. Tannic acid (TA) is a natural, water-soluble polyphenol with antimicrobial and anti-inflammatory properties. This study aimed to investigate the effects of a tannin-containing hydroxypropyl chitin hydrogel (HPCH/TA hydrogel) as an innovative pulp capping material. The physicochemical properties of the composite hydrogels were characterized. The effects of HPCH/TA hydrogel as a pulp capping material were evaluated in vitro and in vivo. The underlying mechanism of the anti-inflammatory effects of HPCH/TA hydrogel was explored. The HPCH/TA hydrogel demonstrated favorable temperature sensitivity, injectability, and antibacterial properties. In vitro, the HPCH/TA hydrogel effectively promoted the proliferation of human dental pulp cells and inhibited interleukin-1β, interleukin-6, and tumor necrosis factor-α expression, possibly by suppressing the nuclear factor kappa-B pathway. In vivo, on the fourth day after capping, the HPCH/TA hydrogel group showed lower inflammatory scores compared to the control and iRoot BP Plus (commercial pulp capping material) group. By the sixth week, complete reparative dentin formation was observed in the HPCH/TA hydrogel group, with no difference in thickness compared to the iRoot BP Plus group. Collectively, the HPCH/TA hydrogel holds promise as a bioactive pulp capping material for promoting the repair of inflamed pulp in vital pulp therapy.

An Injectable Thermosensitive Hydrogel with Antibacterial and Antioxidation Properties for Accelerating Wound Healing.

As a new type of wound dressing, hydrogels have attracted more and more attention. However, traditional hydrogel wound dressings lack inherent antibacterial properties and are difficult to match irregular wounds, which leads to an easy wound bacterial infection. To solve the problems associated with traditional hydrogels, in this research, a thermosensitive hydrogel (PFLD) for wound dressings was developed based on Poloxamer 407 (PF127), lysine (Lys), and 3,4-dihydroxyphenylacetic acid (DOPAC). Rheological tests indicated that the PFLD hydrogel possesses injectability, adaptability to deformation, and sufficient mechanical strength for wound dressing applications. In addition, it could in situ gel at 33 °C, which indicated that the hydrogel could undergo sol-to-gel transition under body temperature. Upon using it in wound treatment, it could adapt to irregular wounds to achieve full coverage of the wound and promote the rapid hemostasis of wound bleeding. Due to the presence of DOPAC in the hydrogel, it exhibited excellent antibacterial and antioxidant properties on the wounds. The skin defect model showed that the wound shrinkage was the fastest after PFLD hydrogel treatment. On day 14, the wound shrinkage rates were 81.68 and 99.77% for the control and PFLD hydrogel groups, respectively. Therefore, the PFLD hydrogel has a broad application prospect as a dressing for the treatment of irregular wounds.

In vivo endocultivation of CAD/CAM hybrid scaffolds in the omentum majus in miniature pigs

PurposeCorrection of bony mandibular defects is a challenge in oral and maxillofacial surgery due to aesthetic and functional requirements. This study investigated the potential of a novel hybrid scaffold for bone regeneration and degradation assessment of the ceramic within the omentum majus over 6 months and the extent to which rhBMP-2 as a growth factor, alone or combined with a hydrogel, affects regeneration. Materials and methodsIn this animal study, 10 Göttingen minipigs each had one scaffold implanted in the greater omentum. Five animals had scaffolds loaded with a collagen hydrogel and rhBMP-2, and the other five animals (control group) had scaffolds loaded with rhBMP-2 only. Fluorochrome injections and computed tomography (CT) were performed regularly. After 6 months, the animals were euthanized, and samples were collected for microCT and histological evaluations. ResultsFluorescent and light microscopic and a CT morphological density evaluation showed continuous bone growth until week 16 in both groups. Regarding the ratio of bone attachment to the Zr02 support struts, the rhBMP-2 loaded collagen hydrogel group showed with 63% a significantly higher attachment (p > 0.001) than the rhBMP-2 control group (49%). ConclusionIn this study, bone growth was induced in all omentum majus specimens until post-operative week 16. Furthermore, hydrogel and rhBMP-2 together resulted in better bone-scaffold integration than rhBMP-2 alone. Further studies should investigate whether implantation of the scaffolds in the jaw after an appropriate period of bone regeneration leads to a stable situation and the desired results.

Accelerated cartilage regeneration through immunomodulation and enhanced chondrogenesis by an extracellular matrix hydrogel encapsulating Kartogenin

Articular cartilage is crucial for the functional integrity of joints yet vulnerable to a spectrum of injuries. The adverse immune microenvironment ensuing from injury, coupled with the intrinsic property of the tissue characterized by limited cellularity, poses a significant challenge to the reconstruction of cartilage defect. In this study, an extracellular matrix hydrogel derived from porcine small intestinal submucosa (SIS) with encapsulation of Kartogenin (KGN) has been designed for the cartilage repair and regeneration. The SIS hydrogel, which possessed a three-dimensional porous structure akin to the natural cartilage, has provided a scaffold essential for the progenitor cells engaged in the repair process and sustained release of KGN. As shown by in vitro experiments, the KGN could recruit host endogenous bone marrow-derived mesenchymal stem cells (BMSCs) and induce them to differentiate into chondrocytes, thus enabling in situ cartilage regeneration without cell transplantation. Notably, the bioactive component of SIS was further revealed to possess excellent immunomodulatory capacity to induce the phenotypic shift from M1 to M2 macrophages, which could enhance the chondrogenic differentiation of BMSCs indirectly. Additionally, in vivo experiments showed that the regenerated tissues of the composite SIS hydrogel group were close to the natural hyaline cartilage. Leveraging the combined effects of KGN and SIS hydrogel, this innovative composite material shows great potential as a biomaterial for effective cartilage repair and regeneration.