The host immune response effecting on biomaterials is critical to determine implant fates and bone regeneration property. Bone marrow stem cells (BMSCs) derived exosomes (Exos) contain multiple biosignal molecules and have been demonstrated to exhibit immunomodulatory functions. Herein, we develop a BMSC-derived Exos–functionalized implant to accelerate bone integration by immunoregulation. BMSC-derived Exos were reversibly incorporated on tannic acid (TA) modified sulfonated polyetheretherketone (SPEEK) via the strong interaction of TA with biomacromolecules. The slowly released Exos from SPEEK can be phagocytosed by co-cultured cells, which could efficiently improve the biocompatibilities of SPEEK. In vitro results showed the Exos loaded SPEEK promoted macrophage M2 polarization via the NF-κB pathway to enhance BMSCs osteogenic differentiation. Further in vivo rat air-pouch model and rat femoral drilling model assessment of Exos loaded SPEEK revealed efficient macrophage M2 polarization, desirable new bone formation, and satisfactory osseointegration. Thus, BMSC-derived Exos–functionalized implant exerted osteoimmunomodulation effect to promote osteogenesis.

The critical effects that impair diabetic wound healing are characterized by poor vascularization and severe peripheral neuropathy. Current management strategies for diabetic wound healing are unsatisfactory, due to the paucity of neurovascular regeneration at the wound site. Importantly, conductivity in skin tissue is reported to be essential for modulating myriad biological processes especially vascular and nerve regeneration. Herein, an extracellular matrix (ECM)-based conductive dressing is synthesized from an interpenetrating polymer network hydrogel composed of gelatin methacryloyl, oxidized chondroitin sulfate (OCS), and OCS-polypyrrole conductive nanoparticles that can promote diabetic wound repairing by enhancing local neurovascular regeneration. The conductive hydrogels combine the advantageous features of water-swollen hydrogels with conductive polymers (CPs) to provide tissue-matching electrical conductivity and mechanical properties for neurovascular regeneration. In vitro and in vivo studies show that the conductive hydrogel can promote neurovascular regeneration by increasing intracellular Ca 2+ concentration, which subsequently promotes phosphorylation of proteins in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways. Furthermore, the conductive hydrogel stimulates full-thickness diabetic wound repair on day 14 by promoting local neurovascular regeneration and collagen deposition. These findings corroborate that the ECM-based conductive interpenetrating network hydrogel dressing significantly promotes wound repairing due to its neurovascular regeneration properties, suggesting that they are suitable candidates for diabetic wound repair.

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Photothermal hydrogel adhesives have yielded promising results for wound closure and infected wound treatment in recent years. However, photothermal hydrogel bioadhesives with on-demand removability without additional nanomaterials-based photothermal agents have rarely been reported in the literature. In this work, an injectable intrinsic photothermal hydrogel bioadhesive with an on-demand removal trait is developed through dynamic cross-linking of gelatin (Gel), tannic acid (TA) quinone, and borax for closing skin incisions and accelerating methicillin-resistant Staphylococcus aureus (MRSA) infected wound healing. The TA quinone containing polyphenol and quinone groups with multifunctional adhesiveness and intrinsic photothermal performance confer the hydrogel adhesive with near-infrared (NIR) responsive antibacterial activity. The cross-linking of pH-sensitive boronic ester (polyphenol−B) and Schiff base bonds endow the hydrogel with great self-healing capacity and on-demand removability. Moreover, the hydrogel possesses good biocompatibility, injectability, and hemostasis. The in vivo experiment in a rat cutaneous incision model and full-thickness MRSA-infected wound model indicate that the smart hydrogel can close wounds efficiently and treat infected ones, demonstrating its superiority in noninvasive treatment of cutaneous incisions and enhancing infected full-thickness wound healing.

Mimicking the natural bone extracellular matrix containing intrinsic topo graphy and electrical signals is an effective way to modulate bone regeneration. However, simultaneously coupling of the intrinsic mechanobiology and electrical cues of implant to modulate bone regeneration remains ignored. Here, the authors report in situ designation of titanium dioxide (TiO 2 ) nanocone/bismuth oxide (Bi 2 O 3 ) nanodot heterojunctions on bone implant surface to electro-biomechanically trigger osseointegration at bone/implant interface. TiO 2 nanocone/Bi 2 O 3 nanodot heterojunctions exhibit built-in electric field at the nanoscale interface and elastic modulus equivalent to that of bone tissue. The nano-heterojunctions significantly promoted the attachment, spreading, and osteogenic differentiation of bone marrow mesenchymal stem cells in vitro, and the osteogenesis in vivo. The authors also show that the effects of nano-heterojunctions on osteogenesis are mediated by yes-associated protein biomechanical signal pathway and intracellular enrichment induced Phosphatidylinositol 3-kinase signal pathway. Their findings highlight the coupling of topographical and electric parameters of biomaterials for modulating cell behaviors.

The vulnerability of hydrogel electronic materials to mechanical damage due to their soft nature has necessitated the development of self‐repairing hydrogel electronics. However, the development of such material with underwater self‐repairing capability as well as excellent mechanical properties for application in aquatic environments is highly challenging and has not yet been fully realized. This study designs a tough and highly efficient underwater self‐repairing supramolecular hydrogel by synergistically combining weak hydrogen bonds (H‐bonds) and strong dipole–dipole interactions. The resultant hydrogel has high stretchability (up to 700%) and toughness (4.45 MJ m−3), and an almost 100% fast strain self‐recovery (10 min). The underwater healing process is rapid and autonomous (98% self‐repair efficiency after 1 h of healing). Supramolecular hydrogels can be developed as soft electronic sensors for physiological signal detection (gestures, breathing, microexpression, and vocalization) and real‐time underwater communication (Morse code). Importantly, the hydrogel sensor can function underwater after mechanical damage because of its highly efficient underwater self‐repairing capability.

Cancer residues around the surgical site remain a significant cause of treatment failure with cancer recurrence. To prevent cancer recurrence and simultaneously repair surgery-caused defects, it is urgent to develop implantable biomaterials with anticancer ability and good biological activity. In this work, a functionalized implant is successfully fabricated by doping the effective anticancer element selenium (Se) into the potassium−sodium niobate piezoceramic, which realizes the wireless combination of electrotherapy and chemotherapy. Herein, we demonstrate that the Se-doped piezoelectric implant can cause mitochondrial damage by increasing intracellular reactive oxygen species levels and then trigger the caspase-3 pathway to significantly promote apoptosis of osteosarcoma cells in vitro. Meanwhile, its good biocompatibility has been verified. These results are of great importance for future deployment of wireless electro-and chemostimulation to modulate biological process around the defective tissue.

Blood vessels play an important role in bone defect repair and growth, and a critical challenge of bone defect repair is the promotion of blood vessel formation. Most of the current methods promote vascularization by adding specific growth factors, which are costly and easy to inactivate. In this study, we developed a covalently cross‐linked aminated bioactive glass nanoparticle‐chondroitin sulfate methacrylate (ABGN‐CSMA) organic‐inorganic composite hydrogel with angiogenic properties. The amino groups of the ABGNs form covalent bonds with the carboxyl groups on CSMA. Surface amination modification of BGNs not only improved the dispersion of BGNs in CSMA but also significantly improved the mechanical properties of the composite hydrogel. The largest storage modulus (1200 Pa), the largest loss modulus (560 Pa) and the strongest resistance to deformation of the hydrogel are seen at 10% concentration of ABGNs. Simultaneously, the local pH stability and sustained ion release of the composite hydrogel are conducive to cell adhesion, proliferation, and angiogenesis. This work provides evidence for the development of covalently cross‐linked organic‐inorganic composite hydrogels with angiogenic properties.