Journal of biomedical materials research. Part B, Applied biomaterials最新文献

Polycaprolactone (PCL) electrospun nanofiber dressings loaded with lipophosphonoxin (LPPO) have shown antibacterial activity and pro-healing potential. To optimize dressing thickness for partial-thickness skin wounds and evaluate translational relevance. We compared PCL dressings with areal weights of 10, 20, and 30 g/m² (with or without 7 wt.% LPPO) in a porcine model using partial-thickness wounds. Standard comparators were Aquacel Ag⁺ (antibacterial control) and Jelonet (standard control). Healing was assessed macroscopically and histologically (hematoxylin and eosin, keratins-10 and -14 immunohistochemistry). Systemic LPPO exposure was measured by LC-MS/MS in plasma and liver. A clinical case (STSG donor site) used a 15 g/m² NANO dressing. Thinner dressings (10 and 20 g/m²), whether unloaded (NANO) or LPPO-loaded (NANO-LPPO), supported rapid re-epithelialization from wound edges and hair follicles and yielded complete closure in wounds, comparable to controls. The 30 g/m² variants of both NANO and NANO-LPPO were associated with persistent inflammation and delayed re-epithelialization. LC-MS/MS showed plasma concentrations of LPPO below the quantification limit and very low liver levels. The clinical case mirrored the porcine findings: timely re-epithelialization of the STSG donor site with 15 g/m² NANO was comparable to Jelonet. Dressing thickness influenced healing quality in the porcine model. Partial-thickness wounds treated with 10-20 g/m² NANO dressings showed superior outcomes compared with 30 g/m², with negligible systemic LPPO exposure. In the clinical case, a 15 g/m² NANO dressing supported timely re-epithelialization of the STSG donor site, comparable to standard care. These findings justify further clinical development of PCL NANO-LPPO dressings.

Pulp capping is vital for maintaining pulp health in restorative dentistry, traditionally using Mineral Trioxide Aggregate (MTA) due to its high bioactivity and biocompatibility. Recently, tricalcium silicate from white Portland cement (TSWPC) has gained attention as a cost-effective alternative. This study investigates how the addition of nanosilica (NS) affects the bioactivity and mechanical properties of a resin-based TSWPC-ZrO₂ formulation for pulp capping. Two formulations, TSWPC-ZrO₂ and TSWPC-SiO₂-ZrO₂, were prepared and tested for compressive strength, flexural strength, and elastic modulus in accordance with ISO 9971-1 and ISO 4049. Hydration-driven bioactivity (pH, Ca²⁺/OH^- release), NIH/3 T3 viability, and cell attachment were monitored for 28 days. NS increased 24 h compressive strength from 105 ± 6 MPa to 116 ± 4 MPa and elastic modulus from 7.19 ± 0.27 GPa to 7.55 ± 0.32 GPa, but reduced flexural strength from 83 ± 5 MPa to 61 ± 7 MPa. Both cements generated alkaline conditions (pH 8.0-9.5) and sustained Ca²⁺ release (≤ 31 mg L^-1), with no significant differences between groups. The NS formulation showed higher cell viability after 72 h (244% ± 22%) and enhanced fibroblast attachment. The results indicate that nanosilica accelerates hydration and improves compressive stiffness without compromising bioactivity, offering a mechanically robust, cost-effective alternative to Mineral Trioxide Aggregate for vital-pulp therapy.

Chronic wounds, such as diabetic foot ulcers (DFUs), venous leg ulcers, and pressure sores, are non-healing or poorly healing wounds that present a clinical and financial burden on the healthcare system. Conventional wound care modalities, including wound dressings, negative pressure therapy, and growth factor delivery, have demonstrated limited success, especially in the case of chronic or refractory wounds. Recently, exosome-containing scaffolds have emerged as a promising strategy for regenerative medicine in chronic wound healing. Exosomes are nano-sized extracellular vesicles containing various bioactive factors that can promote regeneration through their regenerative, anti-inflammatory, angiogenic, and proliferative properties, which are involved in the processes of wound healing. In particular, hydrogels have been identified as a favorable platform for exosome delivery due to their excellent biocompatibility, tunable physicochemical properties, and ECM-mimetic nature. This review will highlight the biology of exosomes, different strategies for the incorporation of exosomes with scaffolds, and advances in scaffold fabrication strategies with a focus on electrospinning and three-dimensional bioprinting. Challenges to clinical translation, such as standardization and regulation of exosomes, and future research perspectives will also be discussed.

This study utilized a novel semi-rigid shell barrier system for bone regeneration in a rabbit's calvarial defects. A semi-rigid shell barrier system (SSBS) is comprised of a semi-rigid shell (SRS) and a covering semi-resorbable membrane (SRM). The rabbit's bilateral calvarial defects were divided into five groups and covered with the SSBS (SRS + SRM), the SRM, the d-PTFE (PF), the collagen membrane (CM), and the empty defect (ED) without grafting material. Bone regeneration capacity was evaluated using new bone volume from micro-CT and bone area from histomorphometry at 4 weeks and 12 weeks post-operatively (six defects per group per time point). At 4 and 12 weeks, the SSBS showed significantly highest bone volumes (24.53% ± 1.34%, 35.96% ± 1.51%) and the SRM (25.23% ± 1.75%, 29.25% ± 2.75%), the PF (18.69% ± 1.32%, 29.72% ± 3.00%), the CM (16.93% ± 1.32%, 26.26% ± 1.97%), and the ED (18.39% ± 2.14, 21.63% ± 2.60%). Histomorphometry of the new bone area also showed the same trend as the bone volume. Histological features of the SSBS and SRM showed substantial new bone formation that nearly bridged the defects, demonstrating effective space-maintaining ability and bone infiltration into the material, indicative of osteoinductive properties. The novel semi-rigid shell barrier system proved good in vivo biocompatibility, bone regeneration capacity, and osteoinductive properties.

Osteoporosis is a highly prevalent systemic skeletal disease and a major risk factor for bone fractures. With the increase in population aging worldwide, the prevalence of osteoporosis has also increased. Nevertheless, there are unmet treatment demands for osteoporosis. Strontium plays a crucial role in bone biomineralization. Naringin is a flavanone glycoside with antiosteoporosis effects. Accordingly, this study synthesized strontium-doped mesoporous hydroxyapatite (Hap-Sr) particles and combined them with naringin (NHap-Sr) for use in osteoporosis treatment. Specifically, mesoporous Hap particles were doped with Sr at various molar ratios (10%, 20%, and 30%) through coprecipitation and then combined with naringin (NHap-Sr). These particles were characterized using X-ray diffractometry, transmission electron microscopy, and Zetasizer analysis. Thermogravimetric analysis was conducted to determine the naringin loading efficiency. Various cell models were used to evaluate the potential cytotoxicity and effects of NHap-Sr on bone turnover markers. The results indicated that Ca²⁺ ions were replaced with Sr²⁺ ions, expanding the Hap crystal lattice. Moreover, Hap-Sr20% was the optimal sample for the formation of a mesoporous structure with a particle size of 740-1600 nm and a naringin loading efficiency of 8.5%. NHap-Sr20% upregulated the mRNA expression levels of alkaline phosphatase, osteocalcin, osteoprotegerin, and receptor activator of nuclear factor kappa-B ligand in osteoblast-like cells without imposing cytotoxic effects or impairing mitochondrial membrane potential, demonstrating its ability to promote bone formation. Overall, combining Sr-doped Hap and naringin is a promising osteoporosis treatment strategy.

This research focuses on creating innovative biogenic cerium oxide nanoparticles with multifunctional capabilities to improve treatment strategies for myocardial infarction and enhance cardiac care. The study specifically examined how curcumin-capped silver nanoparticles (Cur@CeO₂NPs) influence oxidative stress resulting from isoproterenol (ISO)-induced myocardial injury. A range of sophisticated characterization methods, such as UV-vis spectroscopy, FTIR, TEM, and XRD, verified that the environmentally produced Cur@CeO₂NPs had a cubic structure and demonstrated significant interactions with curcumin compounds. In this investigation, adult male Wistar rats were used and divided into three groups: a control group, one subjected to ISO injections, and a third group treated with Cur@CeO₂NPs. After the completion of the experiments, the levels of enzymes CK-MB and LDH were measured, and the expression of inflammatory markers HIF1α, TNF-α, and IL-6 was assessed through quantitative reverse transcription PCR (qRT-PCR). Histological changes in heart tissues resulting from ISO exposure were also evaluated using Hematoxylin and Eosin (H&E) staining. The results revealed a significant reduction in the inflammatory markers TNF-α and IL-6 in the Cur@CeO₂NPs treated group. This outcome validated the anti-inflammatory and antioxidant effects of Cur@CeO₂NPs, suggesting their protective role against cardiac injury. The study concludes that Cur@CeO₂NPs help restore redox balance and reduce inflammation, suggesting their potential protective properties. Nonetheless, further investigations are warranted to clarify their effects on inflammatory responses related to myocardial infarction.

Placental-derived biomaterials are rising in popularity for use in treating severe skin injuries due to their abundant pro-healing factors which result in improved healing outcomes. Clinical use of human-derived placental products, however, is limited by high costs, donor availability, and high variability (due to age, health, and genetic factors). Porcine-derived placental biomaterials have structure and pro-healing factors similar to human placental materials, and can be mass produced on a larger scale, with reduced variability and cost. In this study, porcine-derived placental biomaterials were compared to human-derived placental biomaterials in a full-thickness skin defect rat model. Porcine-derived placental powder (PP), porcine-derived placental membrane (PM), and human-derived amniotic membrane (HM) were tested and compared to no treatment in 36 rats. At 3, 7, and 14 days, rats were euthanized, and defects were excised for H&E and picrosirius red staining. Analyses included wound area measurement, gross inflammation and histological inflammation scoring, qualitative assessments via H&E staining, and quantification of collagen in defects via picrosirius staining over the 14-day healing process. No statistical differences were found between treatment groups at each timepoint for percent difference to adjacent control defect measurements including wound area, histological inflammation scoring, and collagen quantification analyses. PP treated defects had lower gross inflammation scores compared to HM at Day 3 (p = 0.048). Trends observed in wound area measurements, gross and histological inflammation scores, and collagen quantification suggested that PP treated defects induced greater healing efficacy at earlier timepoints. Additionally, PP defects had more rapid and robust crust formation which may have contributed to improved healing outcomes based on reduced inflammation, improved hair follicle growth, re-epithelialization, collagen formation, and protection during wound dressing changes.

The immunotoxicological evaluation of collagen-based medical devices typically relies on wild-type rodent models, but interspecies differences may cause biases in immune response. To address this, we developed a human Type III collagen transgenic mouse model. In accordance with ISO/TS 10993-20 guidelines, we assessed the immunotoxicity of human collagen and recombinant/cell-engineered collagens (CCs) using this model, alongside wild-type controls. The full-length human COL3A1 gene was integrated into C57BL/6J mice, with expression confirmed through mRNA and peptide analysis. Mice were injected with human placental stromal protein (positive control), two recombinant humanized collagens (RC-1, RC-2), and CC. The experimental design adhered to GB/T 16886.20 (ISO 10993-20) and YY/T 1465 standards, with assessments including serum antibody detection at multiple timepoints (0-90 days) and terminal analyses at 30 and 90 days, focusing on splenic lymphocyte subsets and local tissue reactions. Results showed that transgenic mice had lower antibody levels compared to wild-type controls, with wild-type mice displaying significantly higher antibody responses at 60 days. These findings suggest altered immune recognition patterns in transgenic mice. The study also indicated that recombinant/CCs triggered only transient immune responses, with no sustained activation. This model provides new insights for refining immunoevaluation strategies for collagen-based materials.

Effective wound healing requires dressings that support tissue regeneration while combating infection, particularly from multidrug-resistant (MDR) pathogens. This study developed and evaluated a multifunctional nanocomposite wound dressing composed of quail egg white (Qeg-W) and gelatin (GLT) embedded with rGO-ZnO-Ag nanoparticles. Nanocomposite films were prepared by incorporating rGO-ZnO-Ag into Qeg-W and applied to full-thickness skin wounds in rats. Wound closure was monitored over 21 days, and tissue samples were collected for histological assessment. Antimicrobial activity against MDR pathogens was evaluated using inhibition zone and MIC assays. The nanocomposite demonstrated robust antimicrobial activity against S. aureus, E. coli, P. aeruginosa, Salmonella enterica, and C. albicans (inhibition zones 14-30 mm; MICs 150-200 μg/mL). All wounds reached complete closure by day 21; however, NP-treated wounds were associated with significantly reduced scar thickness (~4.5-fold vs. GLT, p < 0.0001), while GLT-Qeg-W + NP wounds showed ~2-fold reduction vs. GLT-Qeg-W (p < 0.01). Histopathological evaluation indicated trends toward improved epidermal restoration and regeneration of dermal glands and hair follicles. Overall, GLT-Qeg-W nanocomposites embedded with rGO-ZnO-Ag nanoparticles exhibited strong standalone antimicrobial activity and were associated with reduced scarring and improved tissue organization. These findings suggest the potential of this sustainable, multifunctional system as a wound dressing, while highlighting the need for further studies to confirm these effects in larger cohorts.

Effective wound healing depends on coordinated fibroblast-macrophage cross-talk that governs the transition from inflammation to regeneration. Here, we evaluated whether a glycosaainoglycan (GAG)-based viscoelastic scaffold composed of chitosan, chondroitin sulfate, and hyaluronic acid (CH-(CS-HA)) can modulate this cross-talk and promote regenerative repair. In vitro coculture studies demonstrated excellent cytocompatibility and significant phenotypic modulation. In fibroblasts, α-SMA (acta2) expression increased ~4.4-fold, and fibronectin (fn1) was markedly upregulated at 96 h in the CH-(CS-HA) + conditioned media (CM) group. Importantly, the Col-I/Col-III (col1a1/col1a3) ratio decreased from ~2.1 to ~1.1 over time, while the TGF-β1/TGF-β3 (tgfb1/tgfb3) ratio shifted from ~2.0 to ~0.7, indicating antifibrotic ECM remodeling. In macrophages, CD86 (Cd86) expression decreased from ~2.8-fold to ~1.5-fold, whereas CD206 (Mrc1) increased from ~3.4-fold to ~6.7-fold between 48 and 96 h, confirming M2 polarization. The TGF-β1/TGF-β3 (tgfb1/tgfb3) ratio similarly declined from ~1.0 to ~0.3, reinforcing an anti-inflammatory phenotype. In a full-thickness rat wound model, CH-(CS-HA) treatment achieved ~91% wound closure by day 17 compared to ~63% in controls. Gene expression in healed tissue showed elevated tgfb3 (~6.4-fold) relative to tgfb1 (~4.3-fold), increased col1a1 (~5.3-fold) with reduced col1a3 (~2.7-fold), and enhanced acta2 and fn1 expression, consistent with organized matrix maturation. Histology confirmed complete re-epithelialization and early hair follicle regeneration. Collectively, these findings demonstrate that CH-(CS-HA) orchestrates immune-stromal cross-talk to promote inflammation resolution, balanced ECM remodeling, and functional tissue regeneration.