Implant failure is primarily caused by infection and dysregulated immune responses, highlighting the need to develop implants with tissue-friendly properties. This study introduces a novel one-step strategy for applying a polyphenol-aminoglycoside (PA) coating on various implant substrates, including titanium, in a simple and efficient manner. The multifunctional PA coating can reduce implant failure through its strong antibacterial, immunomodulatory, and osteoinductive activities. By eliminating bacterial infection, promoting the M2 macrophage phenotype, and restoring oxidative balance, PA-coated implants create a favorable osteoimmune microenvironment that supports the osteogenic differentiation of bone marrow mesenchymal stem cells. Furthermore, the PA-coated implants exhibit potent osseointegration in vivo. Collectively, these findings indicate that surface modification with a PA coating represents a promising strategy to meet the clinical requirements of next-generation dental and orthopedic implants in complex clinical environments.

Background Melasma is a chronic hyperpigmentary disorder with frequent relapse and limited treatment satisfaction. Hydroxy-alpha-sanshool and its derivatives have shown potential in ameliorating photodamage, suggesting possible therapeutic value in melasma. Objective To evaluate the efficacy and safety of topical sanshool and its derivatives in patients with melasma. Methods In this randomized, double-blind, placebo-controlled clinical trial, 68 patients with melasma were assigned to four groups receiving pure sanshool (S), melanin-sanshool (MS), polyphenol-sanshool (PS), or placebo vehicle (NA) once nightly for 12 weeks. Melasma Area and Severity Index (MASI), skin luminance (L-value), and melanin index (MI) were assessed at baseline and at weeks 4, 8, and 12. Results At Week 12, all three sanshool-derived formulations demonstrated significant clinical benefit over placebo. MASI score reductions were -0.87 +/- 0.15 (S), -1.18 +/- 0.15 (MS), and -0.80 +/- 0.15 (PS), versus -0.01 +/- 0.17 in the placebo group (p < 0.001). L-value increased by 0.48 +/- 1.05 (S), 0.91 +/- 1.14 (MS), and 1.06 +/- 0.95 (PS), compared with a slight decrease of -0.23 +/- 1.03 in placebo (p = 0.005). MI decreased by -2.52 +/- 10.91 (S), -7.47 +/- 11.68 (MS), and -5.18 +/- 11.08 (PS), versus an increase of 8.86 +/- 18.95 in placebo (p = 0.009), showing concordant improvements in MASI, skin luminance, and MI. Notably, PS showed the strongest brightening effect (p < 0.001), whereas MS achieved the greatest reduction in pigmentation (p = 0.04). All treatments were well tolerated, and no serious adverse events were observed. Conclusion Topical sanshool-derived formulations significantly improved clinical severity, skin luminance, and pigmentation parameters in patients with melasma compared with placebo. MS and PS formulations showed enhanced effects on selected pigmentation-related outcomes. These findings support the therapeutic potential of sanshool-derived formulations as topical agents for pigmentary skin disorders. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2300077100

Sanshool is a promising skin photoprotective agent with strong UV absorption and great antioxidative activity. However, it faces challenges including poor stability, skin penetration-associated systemic toxicity, and efficacy loss upon chemical modification. To address these issues, amphiphilic hyaluronic acids (HHA) were synthesized and self-assembled to integrate with sanshool via hydrophobic interactions, significantly boosting its photostability by 24

Acne is an inflammatory dermatological disorder largely caused by Cutibacterium acnes (C. acnes), which primarily affects the face, neck, chest, and back, leading to skin impairment. This condition is often associated with post-inflammatory erythema, hyperpigmentation, and scarring, as well as psychosocial and emotional distress. Based on the major pathological characteristics of acne with microbiome colonization, and multiple immune responses, we selected doxycycline, a common clinically used antibiotic and anti-inflammatory drug, and epigallocatechin gallate (EGCG), a polyphenol, to construct topically applicable nanoparticles (NPs). The resulting doxycycline-EGCG (DE) NPs significantly reduced the proportion of dead cells in C. acnes-induced HaCaT cells and demonstrated excellent anti-inflammatory effects through inhibition of NF-κB and STAT3 pathways compared to doxycycline alone. Moreover, the DE NPs exhibited better antibacterial efficacy against C. acnes along with improved antioxidant capacity than doxycycline. In an acne-like mouse model, the DE NPs also effectively suppressed skin inflammation and reduced inflammatory cytokine expression. Overall, this work presents a co-assembly strategy driven by covalent and non-covalent interactions, affording polyphenol-based doxycycline NPs with potent anti-inflammatory, antioxidant and antibacterial properties, and offering new opportunities for safe and effective acne local therapy.

Melanin is widely present in nature and plays vital roles in many physiological processes, and melanin-inspired materials with similar structures and properties have attracted increasing attention in recent years. Although several cases of eumelanin and allomelanin-like polymers have been well documented, there is limited attention given to pyomelanin analogues, a kind of brownish melanin pigments from bacteria and fungi. Herein, a facile and robust strategy has been proposed to fabricate pyomelanin-like nanomaterials with controllable morphologies and uniform sizes via the direct accelerated oxidative polymerization of the monomer homogentisic acid. Additionally, the typical properties of the resulting pyomelanin-like nanoparticles, including photothermal effects, antioxidative abilities, and intracellular biocompatibility were carefully demonstrated, and the infectious wound model was established to confirm their promising therapeutic effects in vivo. This work proposes an innovative approach to fabricate new type of melanin-like polymers with great potential in the biomedical field.

Diabetic kidney disease (DKD) represents a major diabetes-related complication and is among the most important causes of end-stage renal disease (ESRD). Current therapies mainly focus on glycemic control but seldom reverse established renal injury. Berberine (BBR) shows promise for DKD through glucose-lowering, anti-inflammatory, and antioxidant effects, yet its translation is limited by poor bioavailability and rapid metabolism. Here, we developed ZIF-BBR-BPNs, a nanoparticle system that encapsulates BBR in a zeolitic imidazolate framework (ZIF) core and applies an epigallocatechin gallate (EGCG) coating to improve stability, systemic exposure, and renal enrichment. In vitro, ZIF-BBR-BPNs decreased oxidative stress, inflammatory activation, and apoptosis, helping maintain glomerular endothelial cell integrity and function. In vivo, the formulation reduced albuminuria and improved renal inflammation, fibrosis, and glomerular damage, with stronger effects than free BBR or metformin. Notably, the formulation increased systemic exposure and enabled passive renal accumulation, supporting sustained therapeutic activity at injury sites. Overall, this multi-target strategy against metabolic stress, oxidative injury, inflammation, and fibrosis enhances BBR efficacy and supports ZIF-BBR-BPNs as a promising candidate for DKD therapy.

Piezocatalytic tumor therapy represents an emerging approach in cancer treatment, leveraging sonosensitizers to generate reactive oxygen species (ROS) under ultrasound (US) irradiation for effective tumor eradication. However, enhancing ROS production efficiency remains a critical challenge in this field. In this study, SrTiO3 (STO) was selected as the base piezocatalytic material, and its performance was optimized through a combined strategy of lithium doping and oxygen vacancy engineering. The modified material (designated 1.5LSTO) exhibits substantially enhanced local electrical responses. As quantified by PFM, its surface potential and piezoelectric (butterfly-type) amplitude were ∼2.23-fold higher than those of the unmodified sample. The optimally modified material, designated as 1.5LSTO, exhibited a 1.44-fold enhancement in piezocatalytic activity compared to pristine STO under US exposure, enabling efficient generation of hydroxyl radicals (•OH) and superoxide anions (• O 2   - ). In vitro experiments demonstrated significant cytotoxicity of 1.5LSTO against tumor cells. Furthermore, in vivo studies using an intestinal tumor-bearing mouse model confirmed that US-activated 1.5LSTO effectively suppressed tumor proliferation and promoted apoptosis. Notably, lithium doping was found to significantly upregulate CD8+ T cell expression, indicating an immunomodulatory effect. The integration of piezocatalysis with immune activation resulted in a multimodal synergistic therapy that substantially improved overall antitumor efficacy. This work provides an innovative material-based strategy for enhancing tumor treatment through functional modulation and synergistic mechanisms.

Long-term exposure to ultraviolet (UV) radiation can cause sunburn, skin aging, and skin cancers. Conventional sunscreens typically combine organic UV filters and inorganic particles for photoprotection, yet concerns remain regarding skin penetration, systemic effects, and reactive oxygen species generation. Inspired by natural photoprotective mechanisms in plants, we develop a series of all-small-molecule sunscreen hydrogels based on natural polyphenols through a facile one-pot assembly process. The resulting hydrogels exhibit efficient UV shielding with high sun protection factors, strong bioadhesion, antioxidant and antibacterial activities, high visible-light transmittance, and low skin penetration tendency. The hydrogels also demonstrate good environmental stability and effective photoprotection in both mice and Bama miniature pigs. This work highlights the potential of bioinspired all-small-molecule assemblies for efficient and safe photoprotection.

Oral ulcers are the most common disease of the oral mucosa, and the pathogenesis is caused by a local overload of reactive oxygen species (ROS) that precipitates tissue breakdown, which, in turn, leads to the formation of ulcers. Here, we report a one-step oxidative copolymerization strategy to synthesize pH/ROS dual-responsive protocatechualdehyde taurine nanoparticles (PAT NPs) by cross-linking protocatechualdehyde and taurine (Tau). These PAT NPs combine excellent biocompatibility and multiple functions, such as efficient scavenging of free radicals, neutralization of lipopolysaccharide, protection of mitochondria, inhibition of M1 macrophage polarization, promotion of M2 polarization, promotion of anti-inflammatory activity and promotion of cell migration and angiogenesis. The animal ulcer model demonstrated that the PAT NPs can simultaneously inhibit inflammation, promote vascularization, and significantly shorten ulcer healing time, providing a new paradigm for the translation of natural polyphenol-taurine nanomaterials in the field of oral mucosal repair.

Black color is the most typical feature of natural and synthetic melanins, which results from the complex packing and chemical disorder of the molecular structure within melanins. From nature and beyond nature, breaking through the black color boundary, expanding the scope of inherent functions, and establishing clearer structure-function relationship of melanin is necessary but hard due to the inherent chaos structure caused by random covalent coupling and supramolecular assembly. Herein, starting from melanin-inspired monomers, we chose and assembled typical organic acceptor molecules (TCNB/TCNQ) with melanin-inspired donor molecules to prepare a series of colorful melanin-inspired pigments through the co-crystallization strategy. The resulting colorful melanin-inspired pigments exhibited multiple colors and different rod-like morphologies compared with many melanin-like polymers. Particularly, green DHI/TCNQ powder presented excellent photothermal efficiency (similar to 69.8%) for antibacterial application. This work would provide new structure-function tailoring strategy toward the design of melanin-like polymers with highly ordered structures and desirable properties.

Oral mucosal wound repair remains a crucial clinical challenge, as the humid and highly dynamic oral microenvironment creates complex conditions that limit the efficacy of conventional treatment strategies. Bioadhesives have emerged as promising biomaterials that effectively address the key limitations of conventional treatments and open new avenues for oral mucosal wound repair. Herein, an ultrasound-responsive lipoic acid-based bioadhesive with in situ polymerization and targeted adhesion capabilities for oral mucosal wounds has been designed. Lipoic acid (LA) was used as the monomer and dissolved in tris(hydroxymethyl) aminomethane (Tris) solution to prepare the hydrogel precursor. Due to the unique disulfide five-membered ring in LA, the precursor rapidly gelled in situ under ultrasound stimulation after being injected onto oral wounds, ensuring precise and stable adhesion. The results demonstrated that the ultrasound-responsive polylipoic acid (UPLA) hydrogel exhibited appropriate adhesive strength and mechanical properties, while cell experiments indicated that this material possessed satisfactory biocompatibility and could promote the migration of human oral keratinocytes (HOKs). In vivo animal experiments further showed that the hydrogel achieved reliable adhesion to the rat oral mucosa and significantly accelerated wound healing processes. Notably, this therapeutic effect was attributed to the hydrogel's ability to promote epithelial regeneration and restoration of epithelial integrity, while simultaneously reducing local inflammatory responses at the wound site. This UPLA bioadhesive integrates in situ gelation, stable mucosal adhesion, and active wound-healing promotion, thereby providing a novel and promising candidate material for clinical oral mucosal wound repair.

The physical eradication of bacterial biofilms is fundamentally limited by rapid post-treatment regeneration. A strategy that integrates physical destruction with biological suppression is therefore highly coveted. Herein, we introduce a strategy to chemically reprogram magnetic liquid metals (LMs) into intelligent antibiofilm nanocomposites. Through a one-step metal-phenolic coordination, we coat the LM with a natural polyphenol (baicalin, BA), creating a nanoplatform (MBA) that executes a synergistic "destroy-and-pacify" mission. This design establishes a self-reinforcing loop: magnetic actuation provides the mechanical force to breach the biofilm matrix, enhancing the penetration of the BA coating. Concurrently, the BA-mediated inhibition of quorum sensing and EPS synthesis pre-weakens the biofilm, making it more susceptible to physical ablation. This reciprocal potentiation leads to exceptional efficacy, more than doubling the clearance efficiency of mature P. aeruginosa biofilms on implants in a murine model and achieving a level of eradication unattainable by monotherapies. This work establishes a new paradigm for designing smart theranostic microrobots, paving the way for programmable platforms to tackle complex biological barriers.

The significant global burden of periodontitis has increased over the past few decades. However, the regeneration and reconstruction of periodontal tissue remain major challenges in clinical practice. Successful periodontal treatment relies on the regulation of calcium signaling. Bone mesenchymal stem cell-derived exosomes (BMSC Exo) hold great potential for promoting calcium influx to enhance osteogenic differentiation, modulate the inflammatory microenvironment, and promote angiogenesis, but their therapeutic efficiency is limited by inadequate stability. To overcome this problem, a mild and facile approach using protocatechualdehyde was employed to modify BMSC Exo (PA@BMSC Exo) through covalent and noncovalent polyphenolic interactions. The resulting PA@BMSC Exo system enhanced the stability against external stress and augmented its ability to induce intracellular calcium entry. Osteogenesis in human periodontal ligament stem cells (hPDLSCs) and integrated periodontal regeneration in periodontitis were observed following PA@BMSC Exo treatment. Furthermore, these multifunctional PA@BMSC Exo also promoted immunoinflammatory regulation and neovascularization. Bioinformatic analysis based on RNA sequencing (RNA-seq) predicted that the osteogenic differentiation of hPDLSCs was enhanced by calcium influx mediated through the voltage-gated calcium channel Cav3.3. Intracellular Ca2+ levels were further validated in hPDLSCs, as well as in RAW264.7 cells and human umbilical vein endothelial cells (HUVECs). Overall, a facile engineered PA@BMSC Exo system was successfully developed to reverse periodontal destruction by orchestrating calcium signaling and the entire periodontal microenvironment, potentially opening a new avenue for the clinical treatment of chronic periodontitis.

Intracerebral hemorrhage (ICH) is associated with high mortality and disability, and ineffective hematoma resolution contributes substantially to secondary brain injury and poor functional recovery. Although macrophage-mediated erythrophagocytosis has been recognized as an important mechanism for endogenous hematoma clearance, strategies that simultaneously enhance hematoma resolution and remodel the toxic perihematomal milieu remain limited. Herein, we developed a synergistic nanotherapeutic platform based on natural polyphenol-derived nanofibers fabricated through the co-assembly of bexarotene (Bex) and epigallocatechin gallate (EGCG). In this formulation, Bex was incorporated to promote macrophage-mediated erythrophagocytosis, while the EGCG-derived polyphenol scaffold provided antioxidant, anti-inflammatory, and ironmodulating functions to alleviate perihematomal microenvironmental stress. The Bex-EGCG nanofibers enhanced endogenous hematoma clearance, reduced inflammation and oxidative stress, attenuated secondary brain injury, and improved neurological recovery after ICH. Overall, this study presents a dual-functional nanofiber delivery strategy that combines Bex-mediated erythrophagocytosis promotion with polyphenolmediated perihematomal milieu remodeling, providing a multifunctional therapeutic approach for ICH.

Graphitic carbon nitride (g-C3N4) is capable of efficiently absorbing electromagnetic waves in the visible light range, thereby generating reactive oxygen species (ROS) with excellent antibacterial activity. However, the ROS produced by photocatalysis exhibit non-selectivity toward bacterial cells, which may lead to oxidative damage to surrounding tissues during the sterilization process. This inherent limitation has hindered the practical application of g-C3N4 in the biomedical field. In this work, surface modification of g-C3N4 nanomaterials was carried out using polyphenols. The modified g-C3N4 nanomaterials not only displayed a significantly enhanced photocatalytic antibacterial effect but also avoided oxidative damage to normal cells and tissues induced by excessive ROS. Furthermore, the polyphenol layer anchored on the surface of the nanomaterials facilitated the loading and targeted delivery of drugs, enabling a dual antibacterial effect through the synergy of photocatalysis and drug therapy. This synergetic effect further improved the overall antibacterial efficacy and expanded the potential application scope of g-C3N4. Additionally, combining modified g-C3N4 with hydrogels yielded composite hydrogels, which exhibited excellent antibacterial and wound-healing-promoting effects in infected wound repair. This study provides a referenceable strategy for photocatalytic materials in biomedicine.

Oxidative stress is a central pathological driver in diabetic nephropathy (DN), leading to excessive reactive oxygen species (ROS) generation, chronic inflammation and progressive renal fibrosis. Effective modulation of oxidative imbalance thus represents a vital therapeutic strategy for mitigating DN progression. Here, we developed a bioinspired polyphenolic nanoplatform by first constructing polymerized grape seed polyphenol nanoparticles via enzymatic polymerization, followed by supramolecular assembly with the bioactive polyphenol resveratrol. This design combined the intrinsic bioactivity of polyphenols with active resveratrol integration, yielding a stable and biocompatible strategy that alleviated DN and enabled superior restoration of renal structure and function. In diabetic models, it promoted coordinated recovery of renal morphology, key structural proteins and physiological function, suggesting potential advantages for long-term renal protection beyond short-term biochemical improvement. These findings demonstrated that enzymatically engineered polyphenolic nanotherapeutics provided a potent and biocompatible approach for oxidative regulation and functional renal restoration in DN therapy.

Severe hemorrhage and wound inflammation are major risk factors contributing to high mortality after tissue trauma. Therefore, there is an urgent need to develop emergency materials that can rapidly and effectively close wounds while simultaneously controlling bleeding and infection. Although current clinical bioadhesives can fill surgical voids and support tissue repair, they generally lack sufficient adhesive strength and anti-inflammatory properties, which limit their effectiveness in inflammatory wound environments. In this study, a kind of bioadhesive hydrogel was developed using a simple heating and mixing strategy with natural building blocks, including polysaccharides, lipoic acid, and natural polyphenol extracts. Through multiple non-covalent interactions (such as hydrogen bonding and electrostatic interactions), the resulting bioadhesive hydrogels exhibited excellent tissue adhesion and hemostatic properties. Moreover, these hydrogels also demonstrated outstanding anti-inflammatory effects, biocompatibility, and favorable biodegradability, effectively promoting both linear and burn wound healing. This work presents a novel strategy for achieving strong bioadhesion using natural molecules and provides a promising approach for the development of multifunctional wound dressings designed to support tissue regeneration.

Polyphenolic flavonoids have shown promising therapeutic effects in spinal cord injury (SCI) due to their outstanding antioxidative and anti-inflammatory functions. However, some of their inherent physicochemical properties such as poor water solubility, low stability and bioavailability, and strong biological metabolism, severely limit the clinical applications. Moreover, the current polyphenolic flavonoid delivery systems have some problems such as sophisticated preparation processes, low yields, high cost, and lack of targeted traceless release. To address those critical issues, we have proposed a general, facile and robust delivery strategy to prepare functional nanoparticles (NPs) through one-pot assembly of polyphenolic flavonoids and their molecular adaptors. Polyethylene glycol (PEG), one of the most widely used biocompatible polymers, and o-aldehyde phenylboric acid, a kind of small molecule adapters, were selected to form NPs with flavonoids. In addition to excellent anti-inflammatory and antioxidant properties, resulting NPs have also demonstrated possess the targeted enrichment of high reactive oxygen species levels in damaged areas and long-term blood circulation stability, which worked well for SCI therapy. This strategy takes the most commonly used PEG as an example, which can be further applied to many other types of hydrophilic polymers with amino groups, such as polysaccharides, peptides and proteins etc.

Developing adhesive sensor devices for extreme environments necessitates properties like fast preparation, cost-effectiveness, robust environmental adhesion, stability, and superior sensing capabilities, which are in high demand. In this research, ionic liquids with diverse chemical bonds were employed as solvents for copolymerization with lipoic acid (LA) under mild conditions to produce lipoic acid-based ionic gels, leveraging the rapid ring-opening polymerization of LA during heating. The findings indicated that the prepared poly-lipoic acid ionic gels displayed outstanding adhesive strength (120 kPa), rapid self-healing abilities (ca.10 s),exceptional resistance to extreme environmental conditions (-196 degrees C), and remarkable sensing performance (331ms). The developed poly-lipoic acid ionic gel is easy to prepare, exhibits enduring adhesion at ultra-low temperatures, and holds promise for adhesive sensing applications in extreme environments, introducing a novel design strategy for advancing next-generation adhesive materials.