There is an urgent need for more effective wound healing therapies, particularly wound dressings that not only promote wound closure and reduce scar formation but also retain antibacterial properties. Chitosan, a natural copolymer with inherent hemostatic and antibacterial properties, and mesenchymal stem cell derived exosomes, which promote rapid re-epithelialization, collagen maturation, and scar reduction, were integrated into a single biofunctional dressing. This study evaluated the therapeutic efficacy and underlying mechanisms of this combined approach using a porcine full thickness skin excision model. In vitro, chitosan hydrogel effectively inhibited the growth of Escherichia coli and Staphylococcus aureus across various inoculation concentrations. Exosome treatment significantly suppressed the proliferation and migration of human dermal fibroblasts (HDFs), downregulated mRNA expression of collagen types I and III and α-smooth muscle actin, while upregulating basic fibroblast growth factor and elastin. Furthermore, exosomes markedly increased vascular endothelial growth factor and insulin like growth factor levels, while decreasing hepatocyte growth factor production compared to untreated HDF controls. Exosome treatment also attenuated lipopolysaccharide (LPS) induced inflammatory responses in HDFs, as evidenced by reduced interleukin-1β (IL-1β), IL-6, and IL-8 secretion. Similarly, chitosan hydrogel reduced IL-1β, IL-6, IL-8, and tumor necrosis factor-α expression while enhancing IL-10 levels in LPS-stimulated peripheral blood mononuclear cells. In vivo, the combination of chitosan hydrogel and high-concentration exosomes significantly accelerated wound closure, enhanced epithelialization, minimized wound contraction, and prevented infection. Histological analysis revealed more mature and well developed epidermal and dermal structures, increased epithelial thickness, reduced myofibroblast percentage and inflammatory cell infiltration, enhanced angiogenesis, and greater type I collagen deposition in treated wounds. Collectively, these findings demonstrate that the chitosan-exosome composite harnesses natural antibacterial activity, inflammation modulation ability and regenerative capacity, establishing it as a highly promising biomaterial dressing for promoting cutaneous wound healing.
Uncontrolled hemorrhage remains one of the most critical clinical challenges in trauma, surgery, and minimally invasive dental procedures, highlighting the need for advanced hemostatic biomaterials that integrate rapid coagulation, bioactivity, and structural stability. In this study, electrospun PCL/Starch nanofibrous scaffolds loaded with tranexamic acid (TXA) were developed as a multifunctional hemostatic platform, wherein three complementary components are synergistically integrated at the nanoscale: starch as a bioactive, hydrophilic polymer that enhances blood uptake and promotes platelet adhesion; TXA as a potent antifibrinolytic agent that stabilizes fibrin networks and prevents premature clot degradation; and PCL as a mechanically robust polymer that ensures structural integrity during clinical application. While prior TXA-loaded electrospun systems have predominantly relied on chitosan- or PVA-based matrices, these approaches are associated with batch-to-batch variability, elevated cost, and frequent requirement for chemical crosslinking. In contrast, starch is a naturally abundant, low-cost, and fully biodegradable polysaccharide with an intrinsic hemostatic capacity: its high water absorption and porous structure accelerate blood coagulation by concentrating platelets, red blood cells, and coagulation factors at the injury site, thereby activating the coagulation cascade independently of exogenous drug loading. To the best of our knowledge, based on an extensive review of the available literature, this study represents the first systematic investigation of TXA-loaded PCL/Starch electrospun nanofibers for hemostatic applications, addressing a clear and unmet gap in the field: the absence of a multifunctional scaffold that integrates rapid coagulation induction, fibrinolysis inhibition, and structural stability within a single, scalable, and cost-effective fabrication approach.
Chronic diabetic wounds are difficult to treat because persistent oxidative stress, mitochondrial dysfunction, and impaired stromal-vascular communication jointly delay tissue repair. In this study, we developed a bioinspired hyaluronic acid-catechol-PEG-amine (HA-CPA) hydrogel through dynamic Schiff-base crosslinking for topical diabetic wound management. The HA-CPA hydrogel formed a porous, self-supporting network and showed favorable cytocompatibility and hemocompatibility. Owing to catechol-containing moieties, the hydrogel displayed strong antioxidant activity, with more than 80% radical-scavenging efficiency in DPPH and ABTS assays. Under diabetic-mimicking conditions, HA-CPA hydrogel extracts reduced intracellular reactive oxygen species, helped preserve mitochondrial membrane potential, and improved fibroblast migration and endothelial angiogenic behavior, including tube formation. In a streptozotocin-induced diabetic full-thickness wound model, HA-CPA treatment accelerated wound closure, enhanced collagen deposition, and promoted re-epithelialization without detectable systemic toxicity in major organs. These findings indicate that HA-CPA hydrogel provides a practical wound-dressing platform that combines redox regulation, inflammatory microenvironment modulation, cellular protection, and vascular-supportive activity.
Atherosclerosis progression is closely linked to metabolic dysfunction of plaque macrophages, where inducible nitric oxide synthase (iNOS)-mediated pathological nitric oxide (NO) burst is a key driver of inflammation and oxidative stress. This study designed macrophage membrane-camouflaged liposomes (M-AN@Lip) for the co-delivery of nicotinamide mononucleotide (NMN) and L-arginine (L-Arg), aiming to precisely regulate macrophage NO metabolic homeostasis. In vitro experiments demonstrated that M-AN@Lip effectively increased intracellular NO generation while significantly downregulating the expression of the oxidative stress-related enzyme NAD(P)H quinone oxidoreductase 1 (NQO1), suggesting a reprogramming of macrophage NO metabolism from a pathological iNOS-dominated pathway towards a protective one. This metabolic shift was accompanied by clearance of intracellular reactive oxygen species (ROS), enhancement of the endogenous antioxidant enzyme system, and polarization of macrophages towards an anti-inflammatory M2 phenotype. Ultimately, M-AN@Lip significantly inhibited oxidized low-density lipoprotein (ox-LDL) uptake and foam cell formation by downregulating the expression of scavenger receptors (CD36, MSR1, SRB1). This study demonstrates that a biomimetic nano-system can achieve integrated anti-inflammatory, antioxidant, and anti-foam cell forming effects through the synergistic regulation of NO metabolism, offering a promising novel nanotherapeutic strategy for atherosclerosis.
Achilles tendon injury remains a major clinical challenge because of its limited intrinsic healing capacity and the high risk of disorganized extracellular matrix remodeling during repair. In this study, we developed an injectable gelatin methacryloyl (GelMA) hydrogel loaded with GsMTx4, a mechanosensitive ion channel modulator, for sustained local delivery and evaluated its therapeutic potential for Achilles tendon healing in vitro and in vivo. The hydrogel exhibited favorable physicochemical properties, injectability, and local retention capacity. Biological evaluation showed that treatment with this delivery system was associated with improved cell compatibility, reduced matrix degradation, and enhanced expression of tendon-related markers. In the Achilles tendon injury model, local administration promoted histological repair, improved collagen organization, and alleviated pathological changes in the injured tissue. These beneficial effects were accompanied by modulation of extracellular matrix remodeling and mechanosensitive responses. Collectively, these findings suggest that this injectable GelMA hydrogel-based delivery strategy may serve as a promising local therapeutic approach for improving Achilles tendon repair.
Porous magnesium (Mg) can be a promising material for biomedical application especially implants due to their low density, structure and properties comparable to human bones. In the current work, porous Mg composites were fabricated using powder metallurgy technique with tailored porosities using PMMA particles as space holder (30wt.%, 40wt.%, and 50wt.%.) that decompose on sintering leaving porosity behind. Zinc and manganese were added as alloying elements and hydroxyapatite was added as an additive in proportion of 6wt.%, 8wt.%, 10wt.%, and 12wt.% to influence the mechanical and corrosion properties of porous Mg. The density and porosity were calculated for all samples followed by the compression and corrosion test to evaluate their performance. The porous Mg composites with porosities ranging from 29.64 to 51.34% were developed with compressive strength in the order of 2.63-23.01 MPa and corrosion rate of 1.13-0.6 mm/year. The better performance was exhibited by porous Mg composite with 30wt.% of PMMA and 12wt.% of Hydroxyapatite. The findings indicated that mechanical characteristics and corrosion resistance of porous Mg composites can be successfully controlled by alloying and addition of Hydroxyapatite to make them suitable for biomedical applications.
The development of biomaterial scaffolds that combine structural support with biological activation remains critical for bone defect repair. In this study, gelatin-based cryogels (GBCs) that incorporate β-tricalcium phosphate (β-TCP) and hyaluronic acid (HA) were fabricated and optimized to balance porosity and mechanical stability. Increasing the HA concentration increased the water content, swelling ratio, and porosity while reducing the compressive stiffness. The cryogels that contained 0.3% HA exhibited interconnected macropores (200-300 μm after swelling), ∼30% porosity, and a compressive modulus of 3.67 MPa and were selected for biological evaluation. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC)-derived exosomes were incorporated to increase osteogenic bioactivity. Compared with the control treatment, exosome treatment significantly increased MG-63 proliferation, alkaline phosphatase activity, and mineral deposition (p < 0.05). Notably, compared with exosomes alone, exosome-seeded cryogels synergistically increased osteogenic differentiation (p < 0.001). In a rabbit femoral defect model, compared with cryogels without exosomes, exosome-functionalized cryogels promoted denser bone matrix formation and neovascularization. These findings demonstrate that GBCs seeded with exosomes provide a structurally permissive and biologically active microenvironment that improves bone regeneration. This cell-free strategy represents a promising platform for translational bone repair applications.
Exploring biological "orthogonality" between plant and animal kingdoms provides a unique opportunity to mimic biological features of both kingdoms. This novel approach can provide solutions to problems that animal kingdom faces. In this study, we aimed to develop and characterize the Neolamarckia cadamba leaf-derived cellulose scaffolds (NCCS). Fresh Neolamarckia cadamba leaves were decutinized using an n-hexanes-diethyl ether and decellularized using 5% sodium dodecyl sulfate (SDS) for 120h and 2% sodium deoxycholate (SDC) solution for 48h. The leaves incubated in deionized water were acted as controls. Finally, the leaves were bleached in 4% NaOCl solution for 12 h. Histology, DAPI staining, and SEM study of scaffold showed complete decellularization with significantly reduced DNA quantity. Water vapor transmission rate and swelling percentage increased significantly and the scaffolds were hemocompatible. Contact angle revealed a significant increase in hydrophilicity and at maximum load of 2.83 N, percent elongation at break was 0.094 mm/mm. The FT-IR bands were not disturbed, and average roughness (Ra) and root mean square roughness (RMS) (Rq) of NCCS was 193.27 nm and 153.48 nm, respectively. Specific surface area, pore volume, and pore radius of NCCS were increased. The Madin-Darby canine kidney (MDCK) cells were adhered on NCCS and cell viability on decellularized leaf was 88.18% ± 16.12%. Subcutaneously implanted NCCS revealed infiltrated host cells. These characteristics establish NCCS as a sustainable, ethical and cost-effective substitute to mammalian tissue-derived scaffolds for biomedical applications.
Objective: To evaluate the effects of carbon monoxide-releasing molecule-3 (CORM-3) on Enterococcus faecalis biofilm inhibition and eradication, and assess its biosafety. Methods: CO release kinetics were measured by UV spectrophotometry. Mature biofilm eradication was assessed using 72-h biofilm models with crystal violet staining and XTT assay. Colonization inhibition was observed by scanning electron microscopy (SEM). Expression of biofilm-associated genes (esp, gelE, fsrB, cylL) was quantified by RT-qPCR. Cytocompatibility was evaluated in human oral keratinocytes (HOK) and human gingival epithelial cells (HGE). Systemic toxicity was assessed in SD rats through hematological and histopathological analyses. Results: CORM-3 released CO time-dependently with a half-release time of approximately 1.5 min. Treatment with 200 μM and 400 μM CORM-3 achieved biofilm clearance rates of 42.8 ± 5.8% and 65.3 ± 4.7%, with metabolic activity reductions of 38.5 ± 6.2% and 61.7 ± 5.3%, respectively. SEM revealed significantly reduced bacterial adhesion in treated groups. RT-qPCR showed 400 μM CORM-3 downregulated esp, gelE, fsrB, and cylL expression by 64.2%, 68.7%, 55.3%, and 42.1%, respectively. Cell viability remained above 87% after 24 h exposure to 400 μM CORM-3. No hematological abnormalities or organ damage were observed following 7-day intraperitoneal administration. Conclusion: CORM-3 exhibits dual anti-biofilm activity against E. faecalis through controlled CO release, inhibiting bacterial colonization and preventing recolonization while eradicating mature biofilms, with favorable biocompatibility at effective concentrations, supporting its potential as an adjunctive agent in endodontic treatment.
This study compares the in vivo behavior (epidural thickness and complication rate including the development of cerebrospinal fluid fistula, CSF-fistula) of the newer dura sealant HEMOPATCH® (HP) with that of the well-established patch TACHOSIL® (TS) in early postoperative magnetic resonance imaging (MRI) and during the clinical course after supratentorial cranial surgery. This retrospective cohort study included 58 patients with complete datasets (HP group n = 39, TS group n = 19). Inclusion criteria were supratentorial surgery, use of one dura sealant (HP or TS), re-implantation of the bone flap, and MRI within 3 months after surgery. We measured the thickness of the used dura sealant in axial T1-weighted sequences of postoperative MRI on the area of suture (central) and on two peripheral spots. Additionally, we examined the incidence of surgical revisions due to hemorrhage, infection, and wound healing disorders. The mean central thickness of HP and TS were 0.49 cm and 0.55 cm, respectively. This difference in size was not statistically significant (p = 0.066). The peripheral epidural thickness of HP (d = 0.36 cm) was significantly smaller than of TS (d = 0.42 cm; p = 0.014) in one of two points of peripheral measurement. Similarly, the two groups did not differ significantly in the complication rate needing surgical revision, including CSF fistula (HP 3/39 vs TS 3/19; p = 0.34). The biological behavior in terms of growth, swelling, induction of wound healing disorders, hemorrhage, and development of CSF-fistula showed no statistically significant difference within this small descriptive cohort.
Protein-based biomaterials are widely used in tissue engineering and regenerative medicine; however, many conventional materials suffer from limitations including immunogenicity, low stability, and risks associated with animal-derived sources. In this context, keratin derived from human hair has attracted increasing attention due to its inherent biocompatibility and cysteine-rich structure, which provides reactive thiol (-SH) groups suitable for chemical modification. In the present study, reductively extracted keratin was utilized to preserve thiol functionality, enabling site-selective modification via thiol-maleimide chemistry using an aminoethyl maleimide (AEM) linker. Through this approach, heparin, a clinically established anticoagulant, was immobilized onto keratin films under mild aqueous conditions. The resulting keratin-heparin films exhibited effective suppression of thrombin-induced coagulation, whereas unmodified keratin showed no anticoagulant activity. Furthermore, spectroscopic and colorimetric analyses confirmed successful heparin conjugation and surface presentation, and no measurable heparin release was detected, indicating stable surface immobilization. Overall, these results demonstrate that thiol-specific functionalization provides a selective, stable, and animal-free platform for anticoagulant surface modification, highlighting the potential of keratin-based materials for blood-contacting biomedical applications.
In this study, composite hydrogel scaffolds of cellulose nanocrystals (CNC) and β-glucan with poly(acrylic acid) (PAA) were synthesized, and their effects on accelerating skin wound healing were investigated. CNC was extracted from hardwood and β-glucan from oat flour, and after chemical crosslinking and photopolymerization, CNC-g-β-glucan/PAA composite hydrogels were prepared. The scaffolds' biological properties were evaluated using MTT assay, in vitro degradation in simulated wound fluid, DAPI staining, FESEM analysis, histological examinations, and immunofluorescence in an animal model. Biocompatibility results indicated that scaffolds containing β-glucan (particularly samples S2 and S3) showed the highest cell viability compared to other groups (p < 0.01). Degradation studies revealed a relatively rapid degradation profile. Moreover, in wound healing assessment, these scaffolds significantly increased epidermal thickness, reduced inflammatory cells, and enhanced the expression of bioactive markers including Col-1, VEGF, and TGF-β. FESEM observations also revealed proper fibroblast spreading and favorable adhesion on the scaffold surface. Overall, the data suggest that incorporating β-glucan into the CNC network improves biological and regenerative performance, likely mediated in part by its immunomodulatory activity, making CNC-g-β-glucan/PAA scaffolds a promising option for wound healing and skin tissue engineering applications.
Significant craniomaxillofacial (CMF) bone defects after trauma, tumor removal, or congenital disabilities are a major clinical challenge. Therefore, new methods are continually sought to improve treatment effectiveness. In this context, next-generation biomaterials deserve special attention. Sericin, a protein component of silk, demonstrates regenerative potential. Current evidence suggests that sericin actively stimulates osteogenesis by promoting the differentiation of osteoprogenitor cells and upregulating key markers, including Runx2, osteocalcin, and osteopontin. In addition, it exhibits a favorable biocompatibility profile and promising immunomodulatory properties. By exerting anti-inflammatory effects, sericin may promote a pro-healing polarization of M2 macrophages and reduce TNF-α expression. The antimicrobial potential of sericin-based biomaterials is also highlighted, though the evidence remains debated and further validation is needed, particularly for grafts and scaffolds used in CMF regeneration. Sericin also appears to promote angiogenesis and the organized deposition of mineralized extracellular matrix, which are crucial factors in bone regeneration. In preclinical animal models, sericin-based biomaterials have shown statistically significant improvements in the healing of calvarial, alveolar, and long bone defects. Despite these encouraging findings, the translation of sericin into clinical practice remains limited, with only two human studies available, primarily for minor applications in oral surgery. This review summarizes the current literature focusing on sericin-based biomaterials and relates the available evidence to potential applications in CMF regeneration. In a structured manner, it begins with the physical and biological properties of sericin, proceeds to cellular and tissue interactions, and presents preclinical and clinical evidence, critically evaluating the advantages and limitations.
Bone and cartilage regeneration remains a major clinical challenge due to the limited intrinsic repair capacity of musculoskeletal tissues. Biomaterial strategies capable of regulating stem cell behavior at the single-cell level offer new opportunities for precise control of tissue regeneration. Herein, we developed tannic acid-metal (TA-metal) coordination systems incorporating Fe3+, Sr2+, and Mg2+ ions as single-cell nano-coatings to modulate the pericellular microenvironment of bone marrow-derived mesenchymal stem cells (BMSCs). The physicochemical properties of the TA-metal coatings, including protein adsorption, surface morphology, surface charge, ion release behavior, and elemental composition, were systematically characterized. All TA-metal systems formed conformal coatings on individual cells with excellent cytocompatibility and showed detectable retention during early culture. The TA-metal nano-coatings significantly regulated cell morphology and cytoskeletal organization in a metal ion-dependent manner. Notably, TA-Sr and TA-Mg coatings promoted enhanced cell spreading and well-organized actin structures. Tri-lineage differentiation assays revealed distinct lineage-specific regulatory effects. TA-Fe nano-coatings preferentially enhanced adipogenic differentiation, whereas TA-Sr coatings significantly promoted chondrogenic matrix production while supporting osteogenic differentiation. TA-Mg nano-coatings exhibited the strongest osteogenic potential, as evidenced by increased alkaline phosphatase activity and extracellular matrix mineralization. Collectively, these results demonstrate that TA-metal single-cell nano-coatings enable programmable, ion-specific regulation of stem cell fate within an identical coordination framework. This cell-level biomaterial strategy provides a versatile platform for skeletal tissue engineering and cell-based regenerative therapies.
Osteoporosis treatment using alendronate (ALN) is limited by poor oral bioavailability and gastrointestinal side effects. To address this limitation, this study developed a graphene oxide (GO)-enhanced soluble microneedle (MN) system for transdermal administration of ALN to treat osteoporosis. The MNs were fabricated from polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) using a two-step casting method, forming a drug-loaded core-barrier outer layer. The incorporation of GO significantly improved mechanical strength, with penetration efficiency reaching 66∼88%, and enhanced swelling capacity (PP/GO-ALN swelling ratio: 299%). In vitro release studies showed no significant difference between PP-ALN and PP/GO-ALN MNs in a dialysis bag model, while ex vivo skin permeation demonstrated that PP/GO-ALN MNs achieved significantly higher cumulative drug permeation (1069.53 µg/cm2) over 24 h compared to PP-ALN MNs (712.89 µg/cm2). Furthermore, GO conferred notable antibacterial activity, and the PP/GO-ALN formulation synergistically promoted osteoblast proliferation (cell viability: 107.42%, p < 0.05). These findings demonstrate that the GO-ALN MN system possesses mechanical properties, transdermal delivery, antibacterial effects, and biocompatibility. It provides a highly promising non-invasive strategy for the treatment of osteoporosis.
This study aimed to develop a novel topical treatment for Pseudomonas aeruginosa ( P. aeruginosa )-induced bacterial keratitis (BK) using silver nanoparticles (Ag NPs), addressing critical limitations of current antibiotics, such as poor ocular penetration and microbial resistance. Ag NPs were synthesized via silver-cysteine conjugation and characterized by UV-Vis spectroscopy, zeta potential, dynamic light scattering (DLS), TEM, XRD, and XPS. In vitro, the nanoparticles exhibited potent antibacterial activity against P. aeruginosa with minimal cytotoxicity toward human corneal epithelial cells (HCECs). Notably, they also retained observable activity against methicillin-resistant Staphylococcus aureus (MRSA), suggesting potential for addressing drug-resistant infections. In a mouse model of P. aeruginosa -induced bacterial keratitis, topical application of the Ag NPs effectively ameliorated the infection without harming healthy ocular tissues, demonstrating favorable biocompatibility and strong therapeutic potential. Overall, Ag NPs represent a promising topical nanotherapeutic for BK, offering enhanced ocular bioavailability, retained activity against drug-resistant strains, and favorable biocompatibility, highlighting their strong potential for clinical translation in ocular infection management.
Keratin-based electrospun nanofibers have gained increasing attention as promising biomaterials for drug delivery and tissue engineering due to their intrinsic biocompatibility, bioactivity, and controlled biodegradability. Keratin is rich in functional groups and natural cell-recognition motifs, enabling favorable cell-material interactions, including enhanced adhesion, proliferation, and differentiation. When processed into nanofibrous scaffolds via electrospinning, keratin can closely replicate the nanoscale architecture of the native extracellular matrix, offering high surface area and interconnected porosity that support therapeutic loading and tissue regeneration. This review critically summarizes recent progress in the fabrication of keratin-based electrospun nanofibers, with particular emphasis on electrospinning parameters, keratin-polymer blending strategies, and surface modification approaches used to tailor fiber morphology, mechanical properties, and degradation behavior. Methods for incorporating small-molecule drugs, proteins, growth factors, and nanoparticles are discussed, highlighting their influence on encapsulation efficiency, release profiles, and biological performance. Key biomedical applications are reviewed, including wound healing, skin and soft-tissue repair, bone and cartilage regeneration, and localized cancer therapy, where keratin nanofibers have demonstrated improved healing outcomes, reduced infection, and enhanced tissue integration compared with conventional biomaterial systems. Current challenges related to keratin source variability, limited mechanical strength for load-bearing applications, scalability, and regulatory translation are analyzed. Finally, future perspectives are outlined, focusing on hybrid and stimuli-responsive keratin-based nanofibers and sustainable processing strategies, underscoring their potential as clinically relevant platforms for advanced biomaterials applications.
In this study, coatings based on calcium titanate (CT) were applied onto titanium substrates using sol-gel process combined with dip-coating. In addition to physical and chemical characterization, we evaluated the impact of this surface modification on the expression of key genes involved in cell adhesion, extracellular matrix (ECM) remodeling, and early osteogenic commitment in pre-osteoblasts (MC3t3-E1, Subclone 4). X-ray diffraction (XRD) confirmed the presence of cubic alpha-calcium titanate (CaTiO3) strongly bonded to the titanium surface. Although the coating reduced surface roughness, high dipping speeds induced the formation of thicker layers with microcracks due to thermal expansion mismatches. Increased dipping speeds, however, improved surface wettability. Electrochemical analysis revealed enhanced corrosion behavior, attributed to the formation of a stable oxide layer. Biological assays (MTT and crystal violet) confirmed the absence of cytotoxic effects in both direct and indirect contact conditions. Gene expression analysis showed significant upregulation of Itgb1, Fak, Col1a1, and Runx2 in cells cultured with conditioned media from CT-coated surfaces, indicating enhanced integrin-mediated adhesion, ECM deposition, and early osteogenic differentiation. These molecular responses were accompanied by cytoskeletal remodeling, evidenced by increased phosphorylation of cofilin, suggesting enhanced actin filament stabilization. Collectively, sol-gel CT-based layers exhibit beneficial properties as surface coatings and promote a favorable microenvironment for cell adhesion, matrix remodeling, and osteogenic signaling, without inducing cytotoxicity, underscoring their potential for biomedical applications.
Precisely targeting the site of bacterial infection while reducing harm to healthy tissues has turned into the primary aim of bacterial infection treatment. Based on this background, an acidity-triggered aggregation nanomaterial Cu2+/ZIF-8@PDA-GCS (CZPG) based on bimetallic doped metal-organic frameworks was designed. The zinc-based metal-organic framework doped with Cu2+, namely Cu2+/ZIF-8 (CZ), was first synthesized, followed by modification with polydopamine (PDA) and glycol chitosan (GCS) to endow the CZ with photothermal properties and pH-sensitive charge characteristics, respectively. Under normal physiological conditions, the potential value of CZPG is approximately neutral, and it shows poor affinity to normal tissue cells, but the surface potential of CZPG flips to positive potential at the site of acidic bacterial infection. This allows CZPG to aggregate and adhere on the surface of negatively charged bacteria to ensure the spatial accuracy of CDT/PTT and thus enhance the antibacterial effect.
To address the limitations associated with current bone graft materials, particularly the slow resorption of deproteinized bovine bone minerals and the adverse effects of high-dose BMP-2, we developed an innovative tripartite regeneration platform. This platform employs a decalcified dentin matrix (DDM) as a physiological carrier for the spatio-temporal co-delivery of BMP-2 and Nell-1, representing a novel combined strategy. The DDM particles, optimized to a size range of 500-1000 μm through EDTA hierarchical decalcification (achieving 70% decalcification), exhibited a marked increase in pulp tubule diameter, cross-sectional area, and porosity. Scanning electron microscopy (SEM) analysis confirmed that the absence of a smear layer and the presence of uniform tubules facilitated osteoblast infiltration. In a rat model with critical-sized skull defects, the synergistic DBN structure (comprising DDM, BMP-2, and NELL-1) resulted in nearly complete bone regeneration within 8 weeks, significantly enhancing bone volume and bone mineral density. This bionic platform addresses the "bone-induced inflammation paradox" by utilizing the hierarchical topological structure of DDM and the synergistic dynamics of two factors: the rapid release of BMP-2 and the sustained release of NELL-1. This approach surpasses the clinical gold standard and satisfies the FDA's efficacy criteria for the repair of critical size defects.
