Vitronectin is a key extracellular matrix glycoprotein, but the functional contribution of specific residues within its N-terminal region to osteoblast activity remains poorly defined. We engineered a recombinant N-terminal fragment of human vitronectin (rVn-FI; residues 20-149) and performed a comprehensive mapping study using 16 overlapping 12-mer peptides to pinpoint the exact bioactive motifs. rVn-FI significantly promoted adhesion, spreading, and migration in HOS and MG-63 osteoblast-like cells, mediated primarily by αvβ3 and αvβ5 integrins. Peptide mapping revealed that two RGD-containing motifs-Vn-FI-P6 (AECKPQVTRGDV) and Vn-FI-P7 (PQVTRGDVFTMP)-were the sole drivers of this activity. Notably, Vn-FI-P7 exhibited a significantly higher inhibitory potency against cell adhesion to vitronectin than Vn-FI-P6, suggesting that the flanking sequences in Vn-FI-P7 provide a superior conformational context for integrin binding. None of the other 14 peptides showed biological activity, confirming the absence of non-RGD-dependent binding sites within the N-terminal fragment (residues 20-149). These results define the precise functional boundaries of the vitronectin N-terminus for osteoblast interaction. Our findings highlight that the flanking sequences in Vn-FI-P7 provide a superior conformational context for RGD-integrin binding, offering specific peptide targets for enhancing the bioactivity of bone tissue engineering scaffolds.

We engineered a cobalt-doped biphasic calcium phosphate (CoBCP) by combining monetite-derived pyrophosphate and β-tricalcium phosphate (β-TCP) with lattice-incorporated Co2+, and evaluated its physicochemical profile and invitro bioactivity relevant to bone regeneration. Thermoanalytical (TGA/DTA), X-ray diffraction with Rietveld refinement, and FTIR/Raman confirmed monetite-pyrophosphate conversion after calcination, phase-pure β-TCP, and an approximately equimolar Co-containing biphasic composition in CoBCP; SEM/EDX verified appropriate microstructure and cobalt incorporation. Conditioned-medium assays in MC3T3-E1 pre-osteoblasts demonstrated cytocompatibility (MTT, crystal violet) and preserved collective migration (wound healing), with CoBCP, BCP, and CoCaP 1100 matching osteogenic medium in 24-h gap closure. Gene expression revealed that CoBCP selectively coordinated early proliferation and osteogenic-angiogenic programs: CDK2 was strongly induced at 3 and 7 days (≈300-fold at day 7 vs. control), RUNX2 rose across groups with BCP/CoBCP approximating osteogenic medium at day 7, and ALP was disproportionately elevated by CoBCP (~8-fold at day 3; ~400-fold at day 7). VEGF was sensitive among ceramics, with modest induction in CoCaP and CoBCP at day 3 and pronounced upregulation in TCP and BCP at day 7, while HIF-1α was highest in CoCaP at day 7, consistent with hypoxia-mimetic signaling. Cytoskeletal/adhesion transcripts diverged over time: β-TCP/BCP upregulated Src and Cofilin at day 7, whereas CoBCP selectively increased FAK, suggesting maturing focal-adhesion signaling. Gelatin zymography detected MMP-2/-9 activity across all groups with comparable magnitudes during the early window. Collectively, CoBCP provides a cytocompatible, bioactive milieu that synchronizes proliferation, adhesion, osteogenesis, and angiogenesis, supporting its potential use in orthopedic and dental bone regeneration; future work will map cobalt dose-response and ion release, and validate efficacy and safety in direct-contact and invivo models.

Effective skin wound healing requires reliable fixation and infection prevention. Inspired by the inclined papillary structure of the tiger's tongue, we developed a biomimetic microneedle patch that integrates mechanical stability with antibacterial function. The patch was fabricated via thermal pressing of polylactic acid (PLA) microneedles followed by localized drug loading at the microneedle tips. Its design includes a clamping structure, a dual-array of inclined drug-releasing PLA microneedles, a nonwoven fabric base, and a flexible adhesive layer. Invitro tests demonstrated a penetration force of 0.25 N, enhanced fixation through biomimetic interlocking, and controlled drug release for antibacterial effects. Invivo studies using a male Wistar rat model showed that the patch secured wounds, reduced inflammation, and promoted collagen deposition. These results demonstrate that this drug-loaded biomimetic microneedle patch promotes the healing of full-thickness skin wounds and exhibits superior efficacy compared to drug-free biomimetic microneedle treatments. This study advances wound care by combining biomechanical and pharmacological strategies. Future work will optimize biocompatibility and explore clinical applications.

Repairing large bone defects is a significant clinical challenge. In this context, cellulose nanomaterials, such as bacterial nanocellulose (BNC), cellulose nanofibrils (CNF), and cellulose nanocrystals (CNC), have emerged as promising alternatives due to their natural origin and mechanical properties. Particularly noteworthy is their chemical malleability, which thereby confers specific functionalities. This comprehensive literature review evaluates the efficacy of nanocellulose scaffolds for the repair of critical bone defects, with a focus on the impact of surface modifications. The effects of inserting bioactive functional groups and adding metal ions are analyzed invitro and invivo models. The parameters evaluated include material mineralization (production and precipitation of biogenic apatite, Ca/P ratio), cell adhesion and proliferation, bioadsorption, degradation, and toxicity. The results discussed provide valuable insights into the chemical and biological processes of bone formation, supporting a new paradigm: cellulose is no longer just an "eco-friendly filler" but has become a programmable structural scaffold. The trends highlighted in this review open new avenues for the treatment of bone diseases and tissue regeneration.

The vagina is a fibromuscular tube-shaped organ that plays critical roles in menstruation, pregnancy, and female sexual health. Vaginal tissue constituents, including cells and extracellular matrix components, contribute to tissue structure, function, and prevention of injury and pathology. However, much microstructural function remains unknown, including how the fiber-cell and cell-cell interactions influence macromechanical properties. A deeper understanding of these interactions will provide critical information needed to reduce and prevent vaginal pathologies. Our objective for this work is to design a novel tissue-mimicking biomaterial for vaginal tissue engineering, and characterize its biological and mechanical performance in the vaginal microenvironment. We successfully created fiber-reinforced hydrogels of gelatin-elastin electrospun fibers infiltrated with gelatin methacryloyl hydrogels. Further, we extensively characterized its relevant mechanical behavior, including tensile and tear properties. We also demonstrate initial biocompatibility and stability of the composites using primary vaginal epithelial cells in acidic vaginal conditions. This work significantly advances progress in vaginal tissue engineering by developing a physiologically relevant novel material with tunable properties, equipped to investigate biomechanical and cellular mechanisms underlying vaginal function, pathology, and therapeutic intervention.

Osteomyelitis (OM) is caused by the entry of septic cells into bone tissue. Due to systemic antibiotic side effects and drug resistance, local administration is a strategy for treating OM. In this study, a biodegradable, injectable thermosensitive hydrogel containing vancomycin hydrochloride (VA) was developed to reduce drug resistance and prolong the therapeutic efficacy of Staphylococcus aureus by sustained topical delivery of VA. VA was loaded into an injectable butyl glycidyl ether-modified methylcellulose hydrogel (MC-BGE), and VA-loaded MC-BGE hydrogel (VA@MC-BGE) was obtained. The gelation time of VA@MC-BGE at 37°C was approximately 10 min. Invitro, the hydrogel released ~40% of its VA payload within the first 4 days, followed by a sustained release that reached 91.0% cumulative release by Day 28. During this period, mass-loss measurements showed ~67% degradation of the hydrogel. The invitro study showed that the VA@MC-BGE had stronger antimicrobial activity against S. aureus for at least 7 days and could reduce the cytotoxicity of VA with high osteoblast viability (> 85%) over 72 h. VA@MC-BGE inhibited S. aureus infection and improved inflammation and oxidative stress in osteoblasts. The invivo study showed that the hydrogel was able to degrade gradually invivo and that only a small amount of hydrogel remained at 28 days. The hydrogel was also not significantly toxic to major organs. In an OM rat model, injecting the VA@MC-BGE into the site of tibial infection in rats further reduced bone infection and improved bone regeneration compared to free VA. In conclusion, insitu thermosensitive MC-BGE hydrogels encapsulating VA have slow-release properties and good biocompatibility, which are promising for the treatment of OM.

RNAseq analysis showed that human bone marrow stromal cells (BMSCs) express neurogenic factors, including semaphorins 3A and 3C (sema3A; sema3C) when grown on titanium substrates. Sema3A causes BMSCs to differentiate into osteoblasts invitro and promotes osseointegration invivo, suggesting that sema3C may also contribute to peri-implant bone formation. Human BMSCs were cultured on smooth/hydrophobic (PT), microrough/hydrophobic (SLA), and microrough/hydrophilic (modSLA) Ti substrates. Production of sema3C was sensitive to surface characteristics and was mediated by integrins α2, and β1, BMP2, and Wnt5A, but not Wnt11 or sema3A. Sema3C did not affect differentiation of hBMSCs, but inhibited osteoclast differentiation and activity. Conditioned media from hBMSCs grown on modSLA reduced osteoclast differentiation of RAW264.7 cells. Blocking sema3C with anti-sema3C antibodies partially mitigated its inhibitory effect on resorption. However, sema3C did not affect macrophage polarization. Treatment of human umbilical vascular endothelial cells (HUVECs) with modSLA conditioned media increased angiogenesis at 24 h. BMSCs produced sema3C as two variants; the 95 kDa protein was stored in the ECM, whereas the 65 kDa protein was released to the media. Treatment with 65 kDa sema3C inhibited substrate-dependent osteoblastic differentiation of hBMSCs; 95 kDa sema3C had no effect. In conclusion, this study showed that BMSCs produce sema3C in a surface-dependent manner. The 65 kDa sema3C inhibits osteoblast differentiation and the 95 kDa sema3C directly inhibits osteoclastogenesis, resorption, and angiogenesis. Our findings indicate that sema3A and 3C modulate peri-implant bone formation through differential actions on multiple cell types present in the peri-implant environment to promote new bone formation.

Orthopedic biomaterials must both prevent infection and support bone regeneration. To achieve both outcomes with bioactive glass nanoparticles (BGNs), rational nanoarchitectural design is required to decouple and tune silver-ion (Ag+) and calcium-ion (Ca2+) release, balancing antibacterial efficacy with osteogenic compatibility. Herein, we synthesized four BGN types via a modified sol-gel route: solid spheres, Ag-doped solid spheres, core-shell mesoporous BGNs, and Ag-doped core-shell mesoporous BGNs. Core-shell architectures were generated by alkaline etching followed by calcium impregnation, and silver was introduced during synthesis. Comprehensive characterization (scanning/transmission electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy) confirmed homogeneous amorphous glass networks with spatially distinct Ca and Ag distributions in the mesoporous particles. Brunauer-Emmett-Teller analysis showed high-surface-area mesoporous BGNs (≈860 m2/g) versus solid spheres (≈17 m2/g), with markedly greater pore volume. Inductively coupled plasma mass spectrometry revealed sustained Ag+ and Ca2+ release over 21 days within sub-microgram-per-milliliter levels, consistent with the core-shell design. These physicochemical features translated into superior biological performance: Ag-doped mesoporous BGNs accelerated mineralization in simulated body fluid, exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli, and supported the viability and osteogenic differentiation of human mesenchymal stem cells. In ovo biocompatibility testing found no vascular irritation in the Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM). Altogether, nanostructural tuning, particularly combining mesoporosity with a core-shell architecture, can optimize ion-release behavior and biological function in BGNs, advancing multifunctional nanoglasses for regenerative and antimicrobial applications.

Fascia lata (FL) is frequently employed as a grft source in reconstructive surgery. To minimize unwanted responses from the host immune system, several decellularization treatments have been proposed. Effective treatments should aim at avoiding the deterioration of the physical and mechanical properties of the implanted tissue. In this work, we carried out a mechanical characterization of FL specimens from human dead donors, both in their native-physiological condition and upon decellularization with three commonly used detergents, t-octyl-phenoxypolyethoxyethanol (Triton X-100), sodium dodecyl sulfate (SDS), and tri-n-butyl phosphate (TnBP). Uniaxial tensile tests were used to characterize the elastic stiffness and ultimate stresses of the tissue, and Digital Image Correlation (DIC) was applied to monitor the strain evolutions and meso-mechanical deformation responses. None of the investigated decellularization protocols was found to lead to a significant deterioration of the FL mechanical properties, suggesting the applicability of these chemical treatments for graft preparation and usage in clinical practice. The application of DIC also allowed us to get a first estimate of the FL Poisson ratio as well as to draw attention to the inhomogeneity of strain distributions, suggesting that the use of average engineering strains can lead to an oversimplification of the actual deformation field.

Extensive cutaneous injuries with impaired regenerative capacity present substantial risks to both public health and socioeconomic systems. Current skin substitutes remain inadequate in fully replicating native tissue architecture and physiological functionality. While fish skin-derived gelatin-methacrylate (F-GelMA) serves as a principal scaffold material invitro skin models, it has weak mechanical properties and limited mechanical strength, which necessitates supplementation with viscosity-enhancing additives. We created functional invitro 3D extracellular matrix mimics with composite hydrogels based on F-GelMA and the thickener carboxymethyl cellulose (CMC). The physicochemical properties and bioactivity of the hydrogel scaffolds were assessed through testing their rheological properties, swelling behavior, degradation characteristics, and biocompatibility. It was discovered that the F-GelMA/CMC hydrogel bioscaffold loaded with adipose-derived stem cells (ADSCs) expedited wound healing by facilitating wound re-epithelialization, enhancing wound collagen formation, accelerating the deposition of myofibroblasts at the wound site, promoting angiogenesis, stimulating the proliferation and differentiation of keratinocytes, and suppressing skin wound inflammation.