Chronic infected wounds experience delayed healing due to persistent bacterial colonization, excessive accumulation of reactive oxygen species (ROS), and prolonged inflammation. Although adhesive hydrogels are promising as wound dressings, challenges in achieving strong tissue adhesion coupled with adequate internal cohesion have hindered their clinical application. Here, we developed a multifunctional adhesive hydrogel designed around a cohesion–adhesion balance strategy for infected wound treatment. Specifically, we synthesized a gelatin microsphere-reinforced adhesive hydrogel (Gel-GM) by embedding gelatin microspheres (GMs) and the antimicrobial peptide LL-37 into a dopamine-grafted alginate network. Incorporation of GMs strengthened the hydrogel network through increased intermolecular interactions, enhancing cohesive strength while preserving sufficient exposed catechol groups to ensure interfacial adhesion. In vitro studies demonstrated that Gel-GM significantly improves ROS scavenging, promotes anti-inflammatory M2 macrophage polarization, and enhances fibroblast proliferation and migration. Additionally, LL-37 confers potent antibacterial activity by disrupting bacterial membranes via electrostatic interactions. In vivo evaluations revealed that Gel-GM possesses robust antibacterial and anti-inflammatory properties, effectively accelerating infected wound healing. Collectively, this study emphasizes the potential of employing a cohesion–adhesion balance approach to engineer multifunctional adhesive hydrogels for managing infected wounds.

The delicate balance of oral microbiota is frequently disrupted by exogenous discoloration and biofilm formation, thus requiring integrated antibacterial and whitening strategies. Conventional peroxide treatments often damage the integrity of tooth enamel, while nanocatalysts pose cytotoxicity risks. In this work, we designed a biocompatible polydopamine-engineered barium titanate nanocomposite (BTO@PDA_x). By optimizing polydopamine (PDA) shell thickness, BTO@PDA_0.5 exhibited superior excellent piezoelectric catalytic activity. Under ultrasound irradiation, PDA enhanced reactive oxygen species (ROS) generation by promoting charge carrier separation at the BTO interface, thereby accelerating chromogen degradation kinetics. Antibacterial assays and tooth whitening studies confirmed that BTO@PDA_0.5 could effectively inhibit microorganisms and degrade pigments with extremely low cytotoxicity. This study designed a highly biocompatible organic-inorganic composite piezoelectric material, providing a new strategy for oral health care.

Chronic bacterial infections are a key pathological factor hindering wound healing, significantly increasing the incidence of wound sepsis. Existing therapeutic strategies exhibit certain limitations, leading to a continuous decline in clinical efficacy. Therefore, there is an urgent need for the development of novel antibacterial materials to mitigate the risks associated with bacterial infections. In this study, a new antibacterial strategy is proposed, utilizing the flexoelectric polarization of manganese dioxide (MnO₂) nanoflowers (NFs) to generate reactive oxygen species (ROS) at the site of infected wounds, achieving in situ and broad-spectrum bacterial eradication. Upon external ultrasound (US) stimulation, the flexoelectric polarization induced in the MnO₂ NFs results in the generation of abundant ROS on the material surface, which disrupts the integrity of bacterial cell membranes, leading to their inactivation. Compared to conventional photodynamic therapy, this strategy achieves higher ROS generation efficiency (65.3% methylene blue (MB) degradation in 25 min) without light dependency. In vitro experiments confirmed the antibacterial efficacy, with the inactivation rates for Escherichia coli and Staphylococcus aureus reaching 66.22% and 70.67%, respectively. Furthermore, excellent antibacterial effects were observed at the site of infected wounds, promoting wound healing. The integration of the flexoelectric effect into material-based antibacterial strategies holds promise for expanding the range of novel antibacterial materials in the future.

Aging is characterized by the progressive accumulation of molecular and cellular damage, leading to disrupted bone homeostasis and reduced osteogenic potential. Mitochondrial dysfunction, a hallmark of aging, results in elevated reactive oxygen species levels and reduced mitochondrial membrane potential, which significantly impairs osteogenesis of osteoprogenitors cells. Inspired by the naturally occurring intercellular mitochondria transfer during tissue healing process, which activates and enhances cellular reparative functions, this study investigated whether mitochondria replenishment could restore osteogenic capacity of aged human periodontal ligament stem cells (hPDLSCs) and promote bone defect repair. Our findings demonstrate that mitochondria replenishment effectively restores mitochondrial function, enhances osteogenic differentiation of aged hPDLSCs, as well as facilitates bone defect repair in vivo. Mechanistically, mitochondria supplementation upregulates the mitochondrial anchoring protein A-kinase anchoring protein 1 (AKAP1) and activates the cAMP/PKA signaling pathway in mitochondria-receipient hPDLSCs. This study underscores the therapeutic potential of mitochondrial supplementation in reversing aging-related impairments in hPDLSCs and identifies the AKAP1-regulated cAMP/PKA pathway as a key mechanism. These findings offer a promising strategy for overcoming aging-associated challenges in bone regeneration.

Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate, prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy. Thus, the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.

Nano-engineering-based tissue regeneration and local therapeutic delivery strategies show significant potential to reduce the health and economic burden associated with craniofacial defects, including traumas and tumours. Critical to the success of such nano-engineered non-resorbable craniofacial implants include load-bearing functioning and survival in complex local trauma conditions. Further, race to invade between multiple cells and pathogens is an important criterion that dictates the fate of the implant. In this pioneering review, we compare the therapeutic efficacy of nano-engineered titanium-based craniofacial implants towards maximised local therapy addressing bone formation/resorption, soft-tissue integration, bacterial infection and cancers/tumours. We present the various strategies to engineer titanium-based craniofacial implants in the macro-, micro- and nano-scales, using topographical, chemical, electrochemical, biological and therapeutic modifications. A particular focus is electrochemically anodised titanium implants with controlled nanotopographies that enable tailored and enhanced bioactivity and local therapeutic release. Next, we review the clinical translation challenges associated with such implants. This review will inform the readers of the latest developments and challenges related to therapeutic nano-engineered craniofacial implants.