Thermosensitive hydrogel with programmed dual-octenidine release combating biofilm for the treatment of apical periodontitis.

The utilization of intracanal medicaments is an indispensable procedure in root-canal treatment. However, the conventional intracanal medicaments still need improvement regarding antimicrobial efficacy and ease of clinical operation. To address the above issues, OCT/PECT@OCT + ALK composite hydrogel characterized by programming sequential release of dual antimicrobial agents has been proposed. Thanks to the self-assemble ability of amphiphilic copolymer poly(ε-caprolactone-co-1,4,8-trioxa [4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(ε-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT), dual hydrophilic and hydrophobic antimicrobial agents could be easily encapsulated in the hydrogel system and tailored for sequential drug release for a better antibiofilm effect. The hydrophilic octenidine (Octenidine dihydrochloride, OCT-HCl) is encapsulated in the hydrophilic part of hydrogel for instantaneous elevating the drug concentration through bursting release, and the hydrophobic octenidine (Octenidine, OCT) is further loaded into the PECT nanoparticles to achieve a slower and sustained-release profile. Additionally, calcium hydroxide (Ca(OH)2) was incorporated into the system and evenly dispersed among PECT nanoparticles to create an alkaline (ALK) environment, synergistically enhancing the antibiofilm effect with higher efficiency and prolonged duration. The antibiofilm effect has been demonstrated in root-canal models and apical periodontitis rats, exhibiting superior performance compared to clinically used Ca(OH)2 paste. This study demonstrates that OCT/PECT@OCT + ALK composite thermosensitive hydrogel is a potential intracanal medicament with excellent antibiofilm effect and clinical operability.

Bioactive microgel-coated electrospun membrane with cell-instructive interfaces and topology for abdominal wall defect repair.

Current mesh materials used for the clinical treatment of abdominal defects struggle to balance mechanical properties and bioactivity to support tissue remodeling. Therefore, a bioactive microgel-coated electrospinning membrane was designed with the superiority of cell-instructive topology in guiding cell behavior and function for abdominal wall defect reconstruction. The electrostatic spinning technique was employed to prepare a bioabsorbable PLCL fiber membrane with an effective mechanical support. Additionally, decellularized matrix (dECM)-derived bioactive microgels were further coated on the fiber membrane through co-precipitation with dopamine, which was expected to endow cell-instructive hydrophilic interfaces and topological morphologies for cell adhesion. Moreover, the introduction of the dECM into the microgel promoted the myogenic proliferation and differentiation of C2C12 cells. Subsequently, in vivo experiments using a rat abdominal wall defect model demonstrated that the bioactive microgel coating significantly contributed to the reconstruction of intact abdominal wall structures, highlighting its potential for clinical application in promoting the repair of soft tissue defects associated with abdominal wall damage. This study presented an effective mesh material for facilitating the reconstruction of abdominal wall defects and contributed novel design concepts for the surface modification of scaffolds with cell-instructive interfaces and topology.

Bioinspired, Anticoagulative, 19 F MRI-Visualizable Bilayer Hydrogel Tubes as High Patency Small-Diameter Vascular Grafts.

The clinical patency of small-diameter vascular grafts (SDVGs) (ID < 6 mm) is limited, with the formation of mural thrombi being a major threat of this limitation. Herein, a bilayered hydrogel tube based on the essential structure of native blood vessels is developed by optimizing the relation between vascular functions and the molecular structure of hydrogels. The inner layer of the SDVGs comprises a zwitterionic fluorinated hydrogel, avoiding the formation of thromboinflammation-induced mural thrombi. Furthermore, the position and morphology of the SDVGs can be visualized via 19 F/1 H magnetic resonance imaging. The outer poly(N-acryloyl glycinamide) hydrogel layer of SDVGs provides matched mechanical properties with native blood vessels through the multiple and controllable intermolecular hydrogen-bond interactions, which can withstand the accelerated fatigue test under pulsatile radial pressure for 380 million cycles (equal to a service life of 10 years in vivo). Consequently, the SDVGs exhibit higher patency (100%) and more stable morphology following porcine carotid artery transplantation for 9 months and rabbit carotid artery transplantation for 3 months. Therefore, such a bioinspired, antithrombotic, and visualizable SDVG presents a promising design approach for long-term patency products and great potential of helping patients with cardiovascular diseases.

Supramolecular Polymer-Nanomedicine Hydrogel Loaded with Tumor Associated Macrophage-Reprogramming polyTLR7/8a Nanoregulator for Enhanced Anti-Angiogenesis Therapy of Orthotopic Hepatocellular Carcinoma.

Anti-angiogenic therapies targeting inhibition of vascular endothelial growth factor (VEGF) pathway show clinical benefit in hypervascular hepatocellular carcinoma (HCC) tumors. However, HCC expresses massive pro-angiogenic factors in the tumor microenvironment (TME) in response to anti-angiogenic therapy, recruiting tumor-associated macrophages (TAMs), leading to revascularization and tumor progression. To regulate cell types in TME and promote the therapeutic efficiency of anti-angiogenic therapy, a supramolecular hydrogel drug delivery system (PLDX-PMI) co-assembled by anti-angiogenic nanomedicines (PCN-Len nanoparticles (NPs)) and oxidized dextran (DX), and loaded with TAMs-reprogramming polyTLR7/8a nanoregulators (p(Man-IMDQ) NRs) is developed for orthotopic liver cancer therapy. PCN-Len NPs target tyrosine kinases of vascular endothelial cells and blocked VEGFR signaling pathway. p(Man-IMDQ) NRs repolarize pro-angiogenic M2-type TAMs into anti-angiogenic M1-type TAMs via mannose-binding receptors, reducing the secretion of VEGF, which further compromised the migration and proliferation of vascular endothelial cells. On highly malignant orthotopic liver cancer Hepa1-6 model, it is found that a single administration of the hydrogel formulation significantly decreases tumor microvessel density, promotes tumor vascular network maturation, and reduces M2-subtype TAMs, thereby effectively inhibiting tumor progression. Collectively, findings in this work highlight the great significance of TAMs reprogramming in enhancing anti-angiogenesis treatment for orthotopic HCC, and provides an advanced hydrogel delivery system-based synergistic approach for tumor therapy.

Solid SiO2-Sealed Mesoporous Silica for Synergistically Combined Use of Inorganic and Organic Filters to Achieve Safe and Effective Skin Protection from All-Band UV Radiation.

To effectively shield the full band of ultraviolet (UV) radiation and provide desirable protection, the combination of inorganic and organic filters was often used to protect human skin from the serious harm of UV exposure. However, the incompatibility of different filters and their mutual negative effect limit the production of multifilter sunscreen. In addition, the hazard of reactive oxygen species (ROS) produced by inorganic filters after UV exposure and the skin permeability of organic filters remain unresolved problems. In this study, titanium dioxide (TiO2) and diethylamino hydroxybenzoyl hexyl benzoate (DHHB), two kinds of common filters with complementary UV shielding range, were first encapsulated into large mesoporous silica nanoparticles (MSN, ∼300 nm) to obtain MSN-TiO2 and MSN-DHHB. Also, a SiO2 coating was then made to seal and stabilize the MSN-TiO2 and MSN-DHHB. The structure, UV screen function, and safety of the SiO2-coated filters, MSN-TiO2@SiO2 and MSN-DHHB@SiO2, were evaluated. The good mechanical stability exhibited by the solid SiO2 layer prevented the release and skin penetration of the sealed DHHB and the photocatalysis of TiO2. Furthermore, the combination of MSN-TiO2@SiO2 and MSN-DHHB@SiO2 in sunscreen cream showed excellent UV shielding performance on covering the whole UV radiation range without mutual interference. Therefore, coating SiO2 over MSN is a feasible strategy for entrapping various filters to improve their photostability, preventing skin penetration and ROS generation, and enhancing their compatibility with different sunscreen formulations.

Bioinspired and Inflammation-Modulatory Glycopeptide Hydrogels for Radiation-Induced Chronic Skin Injury Repair.

Clinical wound management of radiation-induced skin injury (RSI) remains a great challenge due to acute injuries induced by excessive reactive oxygen species (ROS), and the concomitant repetitive inflammatory microenvironment caused by an imbalance in macrophage homeostasis. Herein, a cutaneous extracellular matrix (ECM)-inspired glycopeptide hydrogel (GK@TAgel ) is rationally designed for accelerating wound healing through modulating the chronic inflammation in RSI. The glycopeptide hydrogel not only replicates ECM-like glycoprotein components and nanofibrous architecture, but also displays effective ROS scavenging and radioprotective capability that can reduce the acute injuries after exposure to irradiation. Importantly, the mannose receptor (MR) in GK@TAgel exhibits high affinity and bioactivity to drive the M2 macrophage polarization, thereby overcoming the persistent inflammatory microenvironment in chronic RSI. The repair of RSI in mice demonstrates that GK@TAgel significantly reduces the hyperplasia of epithelial, promotes appendage regeneration and angiogenesis, and decreased the proinflammatory cytokine expression, which is superior to the treatment of commercial radioprotective drug amifostine. Collectively, the ECM-mimetic hydrogel dressing can protect the tissue from irradiation and heal the chronic wound in RSI, holding great potential in clinical wound management and tissue regeneration.

Skin-Adaptable, Long-Lasting Moisture, and Temperature-Tolerant Hydrogel Dressings for Accelerating Burn Wound Healing without Secondary Damage.

Developing multifunctional wound dressings, possessing not only skin-like mechanical properties and adaptability, long-lasting moisture, and temperature tolerance that maximally mimics the human skin but also on-demand adhesion without unnecessary bleeding and secondary damage upon peeling, is necessary but remains a challenge. Herein, a novel dual cross-linked and multifunctional hydrogel, termed PSNC hydrogel for polymerized sulfobetaine methacrylate (SBMA), N-(2-amino-2-oxyethyl)acrylamide (NAGA), and 1-carboxy-N-methyl-N-di(2-methacryloyloxy-ethyl)methanaminium inner salt (CBMAX), was fabricated as a wound dressing for burn injuries via one-pot radical polymerization in glycerine (GLY)/H2O solvent. The dual cross-linked network of the PSNC hydrogel combined the double hydrogen bonding of N-(2-amino-2-oxyethyl)acrylamide (NAGA) with a covalently cross-linked zwitterionic network, endowing the hydrogel with skin-like mechanical properties with a high stretchability of 1613.8 ± 79.8%, a tensile strength of 77.5 ± 1.8 kPa, and a tensile modulus of 1.9 ± 0.1 kPa. Moreover, the hydrogel with well-developed adaptability can withstand skin deformation without breaking or debonding attributed to its good tissue adhesiveness and self-healing ability. Further, the utilization of the GLY/H2O binary solvent effectively prevented the crystallization and evaporation of free water, endowing the hydrogel with not only long-lasting moisture but also excellent temperature tolerance in a wide range from -20 to 60 °C. More importantly, the PSNC hydrogel could effectively accelerate wound healing of burn injuries and could be easily removed on-demand with saline without causing secondary damage due to intense hydration. Such a novel PSNC zwitterionic hydrogel could be a promising candidate for the treatment of burn wounds and tissue regeneration.