Curcumin-Based Ionic Liquid Hydrogel for Topical Transdermal Delivery of Curcumin To Improve Its Therapeutic Effect on the Psoriasis Mouse Model.

Psoriasis is a systemic, recurrent, chronic autoimmune skin disease. However, psoriasis drugs have poor skin permeability and high toxicity, resulting in low bioavailability and affecting their clinical application. In this study, we propose a curcumin-based ionic liquid hydrogel loaded with ilomastat (Cur-Car-IL@Ilo hydrogel), which can effectively maintain the sustained release of drugs and improve the skin permeability of drugs. We used a model of imiquimod-induced psoriasis and demonstrated that local application of Cur-Car-IL@Ilo hydrogel can improve skin lesions in mice with significantly reduced expression levels of inflammatory factors, matrix metalloproteinase 8, and collagen-I. The expressions of iron death-related proteins SLC7A11 and ASL4 were significantly decreased after treatment with Cur-Car-IL@Ilo hydrogel. Flora analysis showed that the content of anaerotruncus, proteus, and UCG-009 bacteria in the gut of psoriatic mice increased. The levels of paludicola, parabacteroides, prevotellaceae_UCG-001, escherichia-shigella, and aerococcus decreased, and the levels of some of the above bacteria tended to be normal after treatment. Therefore, the curcumin-based ionic liquid hydrogel can be used as a multifunctional, nonirritating, noninvasive, and highly effective percutaneous treatment of psoriasis.

In situ chemoimmunotherapy hydrogel elicits immunogenic cell death and evokes efficient antitumor immune response.

BACKGROUND: Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application. METHODS: Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated. RESULTS: This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses. CONCLUSIONS: Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.

Advanced multifunctional hydrogels for diabetic foot ulcer healing: Active substances and biological functions.

AIM: Hydrogels with excellent biocompatibility and biodegradability can be used as the desirable dressings for the therapy of diabetic foot ulcer (DFU). This review aimed to summarize the biological functions of hydrogels, combining with the pathogenesis of DFU. METHODS: The studies in the last 10 years were searched and summarized from the online database PubMed using a combination of keywords such as hydrogel and diabetes. The biological functions of hydrogels and their healing mechanism on DFU were elaborated. RESULTS: In this review, hydrogels were classified by their active substances such as drugs, cytokines, photosensitizers, and biomimetic peptide. Based on this, the biological functions of hydrogels were summarized by associating the pathogenesis of DFU, including oxidative stress, chronic inflammation, cell phenotype change, vasculopathy, and infection. This review also pointed out some of the shortcomings of hydrogels in present researches. CONCLUSIONS: Hydrogels were classified into carrier hydrogels and self-functioning hydrogels in this review. Besides, the functions and components of existing hydrogels were clarified to provide assistance for future researches and clinical applications.

Biomaterials-Based Strategies to Enhance Angiogenesis in Diabetic Wound Healing.

Amidst the present healthcare issues, diabetes is unique as an emerging class of affliction with chronicity in a majority of the population. To check and control its effects, there have been huge turnover and constant development of management strategies, and though a bigger part of the health care area is involved in achieving its control and the related issues such as the effect of diabetes on wound healing and care and many of the works have reached certain successful outcomes, still there is a huge lack in managing it, with maximum effect yet to be attained. Studying pathophysiology and involvement of various treatment options, such as tissue engineering, application of hydrogels, drug delivery methods, and enhancing angiogenesis, are at constantly developing stages either direct or indirect. In this review, we have gathered a wide field of information and different new therapeutic methods and targets for the scientific community, paving the way toward more settled ideas and research advances to cure diabetic wounds and manage their outcomes.

Advances in Hydrogels for Periodontitis Treatment.

Periodontitis is a common condition characterized by a bacterial infection and the disruption of the body's immune-inflammatory response, which causes damage to the teeth and supporting tissues and eventually results in tooth loss. Current therapy involves the systemic and local administration of antibiotics. However, the existing treatments cannot exert effective, sustained release and maintain an effective therapeutic concentration of the drug at the lesion site. Hydrogels are used to treat periodontitis due to their low cytotoxicity, exceptional water retention capability, and controlled drug release profile. Hydrogels can imitate the extracellular matrix of periodontal cells while offering suitable sites to load antibiotics. This article reviews the utilization of hydrogels for periodontitis therapy based on the pathogenesis and clinical manifestations of the disease. Additionally, the latest therapeutic strategies for smart hydrogels and the main techniques for hydrogel preparation have been discussed. The information will aid in designing and preparing future hydrogels for periodontitis treatment.

Intradermal Injection of Hybrid Complexes of High- and Low-Molecular-Weight Hyaluronan: Where Do We Stand and Where Are We Headed in Regenerative Medicine?

Hyaluronic acid (HA) is a remarkably multifaceted biomacromolecule, playing a role in regulating myriad biological processes such as wound healing, tissue regeneration, anti-inflammation, and immunomodulation. Crosslinked high- and low-molecular-weight hyaluronic acid hydrogels achieve higher molar concentrations, display slower degradation, and allow optimal tissue product diffusion, while harnessing the synergistic contribution of different-molecular-weight hyaluronans. A recent innovation in the world of hyaluronic acid synthesis is represented by NAHYCO® Hybrid Technology, a thermal process leading to hybrid cooperative hyaluronic acid complexes (HCC). This review summarizes the current literature on the in vitro studies and in vivo applications of HCC, from facial and body rejuvenation to future perspectives in skin wound healing, dermatology, and genitourinary pathologies.

In-Hydrogel Cell-Free Protein Expression System as Biocompatible and Implantable Biomaterial.

Biomaterials capable of delivering therapeutic proteins are relevant in biomedicine, yet their manufacturing relies on centralized manufacturing chains that pose challenges to their remote implementation at the point of care. This study explores the viability of confined cell-free protein synthesis within porous hydrogels as biomaterials that dynamically produce and deliver proteins to in vitro and in vivo biological microenvironments. These functional biomaterials have the potential to be assembled as implants at the point of care. To this aim, we first entrap cell-free extracts (CFEs) from Escherichia coli containing the transcription-translation machinery, together with plasmid DNA encoding the super folded green fluorescence protein (sGFP) as a model protein, into hydrogels using various preparation methods. Agarose hydrogels result in the most suitable biomaterials to confine the protein synthesis system, demonstrating efficient sGFP production and diffusion from the core to the surface of the hydrogel. Freeze-drying (FD) of agarose hydrogels still allows for the synthesis and diffusion of sGFP, yielding a more attractive biomaterial for its reconstitution and implementation at the point of care. FD-agarose hydrogels are biocompatible in vitro, allowing for the colonization of cell microenvironments along with cell proliferation. Implantation assays of this biomaterial in a preclinical mouse model proved the feasibility of this protein synthesis approach in an in vivo context and indicated that the physical properties of the biomaterials influence their immune responses. This work introduces a promising avenue for biomaterial fabrication, enabling the in vivo synthesis and targeted delivery of proteins and opening new paths for advanced protein therapeutic approaches based on biocompatible biomaterials.

Encapsulation of the growth factor neurotrophin-3 in heparinised poloxamer hydrogel stabilises bioactivity and provides sustained release.

Poloxamer-based hydrogels show promise to stabilise and sustain the delivery of growth factors in tissue engineering applications, such as following spinal cord injury. Typically, growth factors such as neurotrophin-3 (NT-3) degrade rapidly in solution. Similarly, poloxamer hydrogels also degrade readily and are, therefore, only capable of sustaining the release of a payload over a small number of days. In this study, we focused on optimising a hydrogel formulation, incorporating both poloxamer 188 and 407, for the sustained delivery of bioactive NT-3. Hyaluronic acid blended into the hydrogels significantly reduced the degradation of the gel. We identified an optimal hydrogel composition consisting of 20 % w/w poloxamer 407, 5 % w/w poloxamer 188, 0.6 % w/w NaCl, and 1.5 % w/w hyaluronic acid. Heparin was chemically bound to the poloxamer chains to enhance interactions between the hydrogel and the growth factor. The unmodified and heparin-modified hydrogels exhibited sustained release of NT-3 for 28 days while preserving the bioactivity of NT-3. Moreover, these hydrogels demonstrated excellent cytocompatibility and had properties suitable for injection into the intrathecal space, underscoring their suitability as a growth factor delivery system. The findings presented here contribute valuable insights to the development of effective delivery strategies for therapeutic growth factors for tissue engineering approaches, including the treatment of spinal cord injury.

Bioavailability enhancement of sildenafil citrate via hydrogel-forming microneedle strategy in combination with cyclodextrin complexation.

Sildenafil citrate (SIL) as a first-line treatment for erectile dysfunction is currently reported to have poor solubility and bioavailability. Moreover, SIL undergoes first-pass metabolism when taken orally and its injection can lead to discomfort. In this study, we introduce a novel transdermal delivery system that integrates hydrogel-forming microneedles with the inclusion complex tablet reservoir. The hydrogel-forming microneedle was prepared from a mixture of polymers and crosslinkers through a crosslinking process. Importantly, the formulations showed high swelling capacity (>400 %) and exhibited adequate mechanical and penetration properties (needle height reduction < 10 %), penetrating up to five layers of Parafilm® M (assessed to reach the dermis layer). Furthermore, to improve the solubility of SIL in the reservoir, the SIL was pre-complexed with ß-cyclodextrin. Molecular docking analysis showed that SIL was successfully encapsulated into the ß-cyclodextrin cavity and was the most suitable conformation compared to other CD derivatives. Moreover, to maximize SIL delivery, sodium starch glycolate was also added to the reservoir formulation. As a proof of concept, in vivo studies demonstrated the effectiveness of this concept, resulting in a significant increase in AUC (area under the curve) compared to that obtained after administration of pure SIL oral suspension, inclusion complex, and Viagra® with relative bioavailability > 100 %. Therefore, the approach developed in this study could potentially increase the efficacy of SIL in treating erectile dysfunction by being non-invasive, safe, avoiding first-pass metabolism, and increasing drug bioavailability.

Hydrogel dressings for diabetic foot ulcer: A systematic review and meta-analysis.

AIM: To investigate the differences in utility between conventional dressings and hydrogel dressings for the treatment of diabetic foot ulcer (DFU). METHODS: The PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang databases were systematically searched up to 21 January 2023. Fixed/random-effect models were used to calculate the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) for the effect size analysis, with heterogeneity determined by I2 statistics. Subgroup analyses of different classes of hydrogel were also conducted. RESULTS: A total of 15 randomized controlled trials with 872 patients were eligible for the present analysis. Compared with conventional dressings, hydrogel dressings significantly improved the healing rate (OR 4.09, 95% CI 2.83 to 5.91), shortened the healing time (MD -11.38, 95% CI -13.11 to -9.66), enhanced granulation formation (MD -3.60, 95% CI -4.21 to -3.00) and epithelial formation (MD -2.82, 95% CI -3.19 to -2.46), and reduced the incidence of bacterial infection (OR 0.10, 95% CI 0.05 to 0.18). CONCLUSION: The meta-analysis showed that hydrogel dressings are more effective in treating DFU compared with conventional dressings.

A randomized trial evaluating a novel hydrogel packing system compared to standard packing during image-guided high-dose rate brachytherapy boost for cervical cancer.

INTRODUCTION: The purpose of this prospective randomized trial was to compare the use of a novel vaginal hydrogel packing system (BrachyGel) to standard vaginal packing (VP) during high dose rate (HDR) brachytherapy (BT) for locally advanced cervical cancer (LACC). METHODS: This cross-over study included LACC patients receiving HDR BT boost (intracavitary +/- interstitial). All patients received alternating gauze or BrachyGel VP on Arms A and B. Patients, physicians, and physicists evaluated BT characteristics via a 4-point Likert scale. Adverse events (AEs) were prospectively collected and scored per CTCAE. RESULTS: The 20 patients enrolled. The mean bladder D2cc difference between gauze and BrachyGel in Arm A was 0.117 Gray (Gy) and in Arm B 0.013 Gy. The mean difference in rectum D2cc in Arm A and Arm B was -0.189 Gy and -0.191 Gy, respectively. The mean dose to 90% of the high-risk clinical target volume (HR-CTV) for gauze compared to BrachyGel was -0.032 Gy (95% CI: 0.472, 0.409). Patient-reported discomfort was similar with BrachyGel and gauze ("mild/moderate" 70.0% vs 74.0%, respectively). The clarity of VP was similar between BrachyGel and gauze (86.8% vs 89.7%, respectively). The completeness of VP was more frequently "excellent/good" with BrachyGel (79.0%) compared to gauze (56.4%). The ease of packing was more frequently "extremely easy" with BrachyGel (21.2% vs 0%). No serious AEs were reported. CONCLUSION: This randomized trial found no clinically significant difference in OAR or HR-CTV dosimetry between BrachyGel and standard VP. BrachyGel performed well compared to gauze for the patient and physician use experience.

Enhanced immunomodulation and periodontal regeneration efficacy of subgingivally delivered progranulin-loaded hydrogel as an adjunct to non-surgical treatment for Class II furcation involvement in dogs.

AIM: To evaluate the effect of subgingival delivery of progranulin (PGRN)/gelatin methacryloyl (GelMA) complex as an adjunct to scaling and root planing (SRP) on an experimental periodontitis dog model with Class II furcation involvement (FI). MATERIALS AND METHODS: A Class II FI model was established, and the defects were divided into four treatment groups: (a) no treatment (control); (b) SRP; (c) SRP + GelMA; (d) SRP + PGRN/GelMA. Eight weeks after treatment, periodontal parameters were recorded, gingival crevicular fluid and gingival tissue were collected for ELISA and RT-qPCR, respectively, and mandibular tissue blocks were collected for micro computed tomography (micro-CT) scanning and hematoxylin and eosin (H&E) staining. RESULTS: The SRP + PGRN/GelMA group showed significant improvement in all periodontal parameters compared with those in the other groups. The expression of markers related to M1 macrophage and Th17 cell significantly decreased, and the expression of markers related to M2 macrophage and Treg cell significantly increased in the SRP + PGRN/GelMA group compared with those in the other groups. The volume, quality and area of new bone and the length of new cementum in the root furcation defects of the PGRN/GelMA group were significantly increased compared to those in the other groups. CONCLUSIONS: Subgingival delivery of the PGRN/GelMA complex could be a promising non-surgical adjunctive therapy for anti-inflammation, immunomodulation and periodontal regeneration.

Enhanced delivery of doxorubicin for breast cancer treatment using pH-sensitive starch/PVA/g-C3N4 hydrogel.

This study introduces a starch/PVA/g-C3N4 nanocarrier hydrogel for pH-sensitive DOX delivery in breast cancer. DOX was loaded into the nanocarrier with 44.75 % loading efficiency and 88 % Entrapment Efficiency. The release of DOX from the starch/PVA/g-C3N4 hydrogel was pH-sensitive: DOX was released faster in the acidic environment pertinent to cancer tumors (with a pH level of 5.4) than in the surrounding regular tissue environment carrying a more neutral environment (pH 7.4). The release kinetics analysis, encompassing zero-order, first-order, Higuchi, and Korsmeyer-Peppas models, revealed significant fitting with the Higuchi model at both pH 5.4 (R2 = 0.99, K = 9.89) and pH 7.4 (R2 = 0.99, K = 5.70) levels. Finally, we found that hydrogel was less damaging to healthy cells and more specific to apoptotic cells than the drug's free form. The starch/PVA/g-C3N4 hydrogel had low toxicity for both normal cells and breast cancer cells, whereas DOX loaded into the starch/PVA/g-C3N4 hydrogel had higher toxicity for cancer cells than the DOX-only control samples, and led to specific high apoptosis for cancer cells. The study suggests that DOX can be loaded into a starch/PVA/g-C3N4 hydrogel to improve the specificity of the drug's release in cancer tumors or in vitro breast cancer cells.

In vitro and in vivo anti-inflammatory properties of an active fucoidan fraction from Sargassum fusiforme and a fraction-based hydrogel.

In a previous study, we separated an active fucoidan (JHCF4) from acid-processed Sargassum fusiforme, then analyzed and confirmed its structure. In the present study, we investigated the potential anti-inflammatory properties of JHCF4 and a JHCF4-based hydrogel in vitro and in vivo. JHCF4 reliably inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages, with an IC50 of 22.35 µg/ml. Furthermore, JHCF4 attenuated the secretion of prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, indicating that JHCF4 regulates inflammatory reactions. In addition, JHCF4 downregulated iNOS and COX-2 and inhibited the activation of the MAPK pathway. According to further in vivo analyses, JHCF4 significantly reduced the generation of reactive oxygen species (ROS), NO production, and cell death in an LPS-induced zebrafish model, suggesting that JHCF4 exhibits anti-inflammatory effects. Additionally, a JHCF4-based hydrogel was developed, and its properties were evaluated. The hydrogel significantly decreased inflammatory and nociceptive responses in carrageenan (carr)-induced mouse paws by reducing the increase in paw thickness and decreasing neutrophil infiltration in the basal and subcutaneous layers of the toe epidermis. These results indicate that JHCF4 exhibits potential anti-inflammatory activity in vitro and in vivo and that JHCF4-based hydrogels have application prospects in the cosmetic and pharmaceutical fields.

Ferrous sulphate triggers ferroptosis in Candida albicans and cures vulvovaginal candidiasis in a mouse model.

Candida albicans is the most leading cause of life-threatening fungal invasive infections, especially for vulvovaginal candidiasis (VVC). Resistance and tolerance to common fungicide has risen great demands on alternative strategies for treating C. albicans infections. In the present study, ferroptosis has been proven to occur in C. albicans by directly exposed to FeSO4 via induing hallmarks of ferroptosis, including Fe2+ overload burden, ROS eruption and lipid peroxidation. Transcriptomic profile gave the great hints of the possible mechanism for fungal ferroptosis that FeSO4 disturb pathways associated to ribosome, tyrosine metabolism, triglyceride metabolism and thiamine metabolism, thus mobilizing death-related gene synthesis. Inspired by the results, a FeSO4-loaded hydrogel was prepared as an antifungal agent to treat C. albicans infection. This hydrogel exhibited excellent dressing properties and maintained superior antifungal activity by characterization tests. Besides, mice treated by this composite hydrogel displayed excellent therapeutic efficacy. These results highlighted the potential therapeutic use of FeSO4 as an innovative strategy in treating C. albicans infections by targeting ferroptosis.

Advances and Trends of Photoresponsive Hydrogels for Bone Tissue Engineering.

The development of static hydrogels as an optimal choice for bone tissue engineering (BTE) remains a difficult challenge primarily due to the intricate nature of bone healing processes, continuous physiological functions, and pathological changes. Hence, there is an urgent need to exploit smart hydrogels with programmable properties that can effectively enhance bone regeneration. Increasing evidence suggests that photoresponsive hydrogels are promising bioscaffolds for BTE due to their advantages such as controlled drug release, cell fate modulation, and the photothermal effect. Here, we review the current advances in photoresponsive hydrogels. The mechanism of photoresponsiveness and its advanced applications in bone repair are also elucidated. Future research would focus on the development of more efficient, safer, and smarter photoresponsive hydrogels for BTE. This review is aimed at offering comprehensive guidance on the trends of photoresponsive hydrogels and shedding light on their potential clinical application in BTE.

Injectable and Conductive Nanomicelle Hydrogel with α-Tocopherol Encapsulation for Enhanced Myocardial Infarction Repair.

Substantial advancements have been achieved in the realm of cardiac tissue repair utilizing functional hydrogel materials. Additionally, drug-loaded hydrogels have emerged as a research hotspot for modulating adverse microenvironments and preventing left ventricular remodeling after myocardial infarction (MI), thereby fostering improved reparative outcomes. In this study, diacrylated Pluronic F127 micelles were used as macro-cross-linkers for the hydrogel, and the hydrophobic drug α-tocopherol (α-TOH) was loaded. Through the in situ synthesis of polydopamine (PDA) and the incorporation of conductive components, an injectable and highly compliant antioxidant/conductive composite FPDA hydrogel was constructed. The hydrogel exhibited exceptional stretchability, high toughness, good conductivity, cell affinity, and tissue adhesion. In a rabbit model, the material was surgically implanted onto the myocardial tissue, subsequent to the ligation of the left anterior descending coronary artery. Four weeks postimplantation, there was discernible functional recovery, manifesting as augmented fractional shortening and ejection fraction, alongside reduced infarcted areas. The findings of this investigation underscore the substantial utility of FPDA hydrogels given their proactive capacity to modulate the post-MI infarct microenvironment and thereby enhance the therapeutic outcomes of myocardial infarction.

Polyvinyl alcohol hydrogel implant for the treatment of hallux rigidus is associated with a high complication rate and moderate failure rate at short-term follow-up: a systematic review.

PURPOSE: Moderate-to-severe hallux rigidus is a debilitating pathology that is optimally treated with surgical intervention. Arthrodesis produces reliable clinical outcomes but is limited by restriction in 1st metatarsophalangeal joint range of motion. The advent of polyvinyl alcohol hydrogel (PVA) implants have produced early promise based on initial trials, but more recent studies have called into question the efficacy of this procedure. The purpose of this systematic review was to evaluate the clinical and radiological outcomes following the use of PVA for hallux rigidus. METHODS: The MEDLINE, EMBASE and Cochrane library databases were systematically reviewed using the preferred reporting items for systematic reviews and meta-analyses guidelines. 18 studies were included. RESULTS: In total, 1349 patients (1367 feet) underwent PVA at a weighted mean follow-up of 24.1 ± 11.1 months. There were 168 patients (169 feet) included in the cheilectomy cohort and 322 patients (322 feet) included in the arthrodesis cohort. All 3 cohorts produced comparable improvements in subjective clinical outcomes. Postoperative imaging findings in the PVA cohort included joint space narrowing, peri-implant fluid, peri-implant edema and erosion of the proximal phalanx. The complication rate in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 27.9%, 11.8% and 24.1%, respectively. The failure rates in the PVA cohort, cheilectomy cohort and arthrodesis cohort was 14.8%, 0.3% and 9.0%, respectively. CONCLUSION: This systematic review demonstrated that PVA produced a high complication rate (27.9%) together with concerning postoperative imaging findings at short-term follow-up. In addition, a moderate failure rate (14.8%) and secondary surgical procedure rate (9.5%) was noted for the PVA cohort. The findings of this review calls into question the efficacy and safety of PVA for the treatment of hallux rigidus. LEVEL OF EVIDENCE: IV.

Perspective insights into versatile hydrogels for stroke: From molecular mechanisms to functional applications.

As the leading killer of life and health, stroke leads to limb paralysis, speech disorder, dysphagia, cognitive impairment, mental depression and other symptoms, which entail a significant financial burden to society and families. At present, physiology, clinical medicine, engineering, and materials science, advanced biomaterials standing on the foothold of these interdisciplinary disciplines provide new opportunities and possibilities for the cure of stroke. Among them, hydrogels have been endowed with more possibilities. It is well-known that hydrogels can be employed as potential biosensors, medication delivery vectors, and cell transporters or matrices in tissue engineering in tissue engineering, and outperform many traditional therapeutic drugs, surgery, and materials. Therefore, hydrogels become a popular scaffolding treatment option for stroke. Diverse synthetic hydrogels were designed according to different pathophysiological mechanisms from the recently reported literature will be thoroughly explored. The biological uses of several types of hydrogels will be highlighted, including pro-angiogenesis, pro-neurogenesis, anti-oxidation, anti-inflammation and anti-apoptosis. Finally, considerations and challenges of using hydrogels in the treatment of stroke are summarized.

Characterization and application of in situ curcumin/ZNP hydrogels for periodontitis treatment.

BACKGROUND: Periodontitis is a chronic inflammatory disease that occurs in tooth-supporting tissues. Controlling inflammation and alleviating periodontal tissue destruction are key factors in periodontal therapy. This study aimed to develop an in situ curcumin/zinc oxide (Cur/ZNP) hydrogel and investigate its characteristics and effectiveness in the treatment of periodontitis. METHODS: Antibacterial activity and cytotoxicity assays were performed in vitro. To evaluate the effect of the in situ Cur/ZNP hydrogel on periodontitis in vivo, an experimental periodontitis model was established in Sprague‒Dawley rats via silk ligature and inoculation of the maxillary first molar with Porphyromonas gingivalis. After one month of in situ treatment with the hydrogel, we examined the transcriptional responses of the gingiva to the Cur/ZNP hydrogel treatment and detected the alveolar bone level as well as the expression of osteocalcin (OCN) and osteoprotegerin (OPG) in the periodontal tissues of the rats. RESULTS: Cur/ZNPs had synergistic inhibitory effects on P. gingivalis and good biocompatibility. RNA sequencing of the gingiva showed that immune effector process-related genes were significantly induced by experimental periodontitis. Carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1), which is involved in the negative regulation of bone resorption, was differentially regulated by the Cur/ZNP hydrogel but not by the Cur hydrogel or ZNP hydrogel. The Cur/ZNP hydrogel also had a stronger protective effect on alveolar bone resorption than both the Cur hydrogel and the ZNP hydrogel. CONCLUSION: The Cur/ZNP hydrogel effectively inhibited periodontal pathogenic bacteria and alleviated alveolar bone destruction while exhibiting favorable biocompatibility.