Journal of biomedical materials research. Part A最新文献

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.

Additive manufacturing (AM) can create orthopedic devices with integrated porosity that enables bone fixation post-implantation. While porosity is key in promoting bone ingrowth and long-term fixation, the device must provide adequate mechanical strength and functionality. Since AM process parameters dictate the final mechanical performance of printed parts, identifying key process parameter levels that preserve or improve such behavior in load-bearing devices with integrated porosity is essential. Using a Taguchi design of experiments, gyroid-structured polyether-ether-ketone (PEEK) and polyether-ketone-ketone (PEKK) specimens were fabricated via fused filament fabrication (FFF) AM to examine the impact of nozzle temperature (T_N), chamber temperature (T_Ch), and layer height (LH) on their compressive mechanical behavior. In addition to compression testing, the printed specimens were analyzed using optical microscopy, scanning electron microscopy, and micro-computed tomography. Elevated processing conditions, specifically high T_Ch combined with thick LH, can enhance heat retention, slow crystallization, increase strut thickness, and improve bonding at strut junctions, enabling porous PEEK and PEKK to withstand higher compressive loads. The elastic moduli of all the porous specimens were more sensitive to variations in processing conditions than their yield strength. Notably, the more amorphous PEKK specimens achieved over 87%-88% of PEEK's calculated elastic modulus in this study and 87%-90% of the yield strength without undergoing annealing. These results are promising, considering that, like PEEK, the elastic modulus of the porous PEKK fell within the range of trabecular bone, while its yield strength surpassed that of trabecular bone.

Chronic wounds and bacterial infections present significant challenges in tissue regeneration, demanding the development of advanced bioactive materials that balance biocompatibility, antimicrobial activity, and tunable physical properties. This study explores the multifunctional role of phytic acid (PA) when incorporated into biopolymer films based on konjac glucomannan (KG) and hyaluronic acid (HA), focusing on how the matrix composition modulates PA's effects on film properties relevant to biomedical applications. PA incorporation significantly influenced water uptake, mechanical strength, and surface characteristics in a matrix-dependent manner. In HA-based films, PA promoted matrix compaction, reduced water content, and enhanced antioxidant activity, whereas in KG-based films, PA induced an increase in water retention and less pronounced antioxidant effects. Surface energy and wettability were favorably altered by PA in both systems, supporting potential improvements in cell-material interactions. Cytocompatibility assays confirmed the nontoxic nature of the films, with KG-based formulations demonstrating higher metabolic compatibility. Notably, PA incorporation suppressed bacterial metabolic activity in Pseudomonas aeruginosa and Escherichia coli, especially in HA-based matrices, while Staphylococcus aureus remained largely unaffected. These results underscore the potential of PA as a tunable additive and natural crosslinking agent and highlight the importance of polymer selection in optimizing film functionality. Finally, this work offers valuable insights into the development of sustainable, bioactive materials suitable for tissue engineering such as wound healing.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population, with no curative treatment currently available. Current therapies primarily target late-stage symptoms and are limited by their frequent and invasive intravitreal (IVT) injections. To address oxidative stress-induced inflammation mechanisms relevant to early retinal degeneration, we developed a heme-bound human serum albumin (heme-albumin) complex designed to transiently induce heme oxygenase-1 (HO-1), a cytoprotective enzyme with antioxidant and anti-inflammatory effects. Polydopamine nanoparticles (PDA NPs) were selected as a delivery system due to their ability to scavenge reactive oxygen species (ROS) and degrade under oxidative environments. A previous in vitro study demonstrated that heme-albumin-loaded PDA NPs reduce oxidative damage and inflammatory signaling in retinal pigment epithelium (RPE) cells. This study evaluates the in vivo biocompatibility of IVT-administered heme-albumin and unloaded PDA NPs as independent components in a murine model. At the tested doses, both components showed minimal cytotoxicity with preservation of retinal structure, establishing biocompatible dosing for future evaluation in retinal disease models.

Electrospun silk fibroin (SF)/poly(vinyl alcohol) (PVA) nanofibrous mats co-loaded with teicoplanin (Tp) and nanoliposomal curcumin (LC) were fabricated to combine extracellular matrix (ECM) mimetic architecture with dual antimicrobial and regenerative functionality. Tp and LC were homogeneously incorporated into SF and PVA, respectively, and electrospun under optimized voltage and flow conditions to yield defect-free fibers. Morphological analysis confirmed a consistent nanofiber diameter and a water uptake of 364.17% ± 42.25%, while in vitro degradation in PBS progressed to 45.74% ± 3.99% mass loss after 28 days. Tensile testing demonstrated a breaking strength of 5.39 MPa, indicating sufficient mechanical integrity for wound application. Drug-release assays revealed a biphasic profile for Tp-an initial burst of 666.31 ± 6.85 μg/mL within the first 24 h, followed by sustained liberation over 4 weeks-whereas curcumin exhibited a steady release rate. Cytocompatibility studies on dermal fibroblasts showed 80.88% ± 1.60% viability, and hemolysis remained below 0.13% ± 0.03%, confirming hemocompatibility. In antimicrobial evaluations, the composite dressings achieved synergistic antibactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa, outperforming single-agent controls. These findings substantiate the T@S/LC@P scaffold as a versatile, infection-resistant dressing, promising accelerated wound healing and preventing microbial colonization.

Glycosaminoglycans (GAGs) like chondroitin sulfate (CS) influence both mechanical properties and biological signals within the tissue microenvironment. CS modifications have been prevalent in a range of biomaterial design strategies, particularly those with a focus on wound healing. Here, we investigate the impact of CS incorporation within a thiolated gelatin (Gel-SH) hydrogel previously established as a promising biomaterial for tendon-to-bone entheseal repair, reporting a dual biological and mechanical effect. We show that CS inclusion increases mesenchymal stem cell metabolic activity and osteo-tendinous differentiation patterns in the Gel-SH biomaterial. Additionally, we demonstrate that inclusion of CS into a Gel-SH hydrogel insertional zone used to link dissimilar tendon and bone specific collagen scaffolds induces favorable local changes in stress-strain behavior. We further show that the mode of incorporation, free incorporation of CS versus covalent tethering of oxidized CS (CSO), clearly impacts these observed effects. Overall, these results highlight promising new motifs to modulate Gel-SH hydrogels for greater promotion of enthesis-associated behavior in resident hMSCs; further, they offer broad insight into design strategies and key considerations for modification of multicompartment materials, namely in consideration of incorporation methods and on the interplay of mechanical and biological properties.

Multidrug-resistant bacterial infections pose a significant challenge in bone tissue engineering, primarily due to the formation of biofilms on implant surfaces, which can impede osteointegration. KR-12, a cationic antimicrobial peptide (AMP) with dual osteoinductive and biofilm-inhibitory properties, represents a promising strategy to address this issue. Poly(lactic-co-glycolic acid) (PLGA) electrospun nanofiber (NF) scaffolds offer biocompatibility, tunable morphology, and support for cell adhesion and proliferation, making them ideal for bone regeneration. While cold atmospheric plasma (CAP) treatment has been explored to enhance peptide functionalization, covalent conjugation of KR-12 to PLGA electrospun NFs has not yet been reported. In this study, KR-12 was incorporated into electrospun PLGA NFs to create a dual-functional scaffold that promotes osteogenic differentiation while inhibiting biofilm formation. Scaffold surface properties were characterized by scanning electron microscopy (SEM) and contact angle measurements, and peptide incorporation was confirmed via fluorescein isothiocyanate (FITC) labeling and FTIR spectroscopy. Human bone marrow-derived mesenchymal stem cells cultured on KR-12-functionalized NFs exhibited enhanced alkaline phosphatase (ALP) activity, calcium and collagen deposition, and upregulated expression of collagen type I (COL1), osteopontin (OPN), and osteocalcin (OCN), as well as positive immunofluorescence staining. Antibacterial and biofilm formation inhibition activities were evaluated against multidrug-resistant MRSA and P. aeruginosa, as well as non-MDR E. coli and S. aureus, demonstrating potent inhibition of biofilm formation. KR-12-functionalized PLGA NFs thus provide a dual-functional platform for infection-resistant bone tissue regeneration, combining osteogenic support with potent inhibition of biofilm formation.

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 in vitro and in vivo 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 development of bone regenerative substitutes capable of orchestrating osteogenesis within inflammatory immune microenvironments remains a critical challenge. This study investigates the dual-functional immunomodulatory peptide DP7-C as a microRNA (miRNA) co-delivery system to regulate osteogenic differentiation and macrophage polarization synchronously. Through systematic screening of DP7-C/miRNA nanocomplexes (miR-21, -26a, -29a, -34a, -124, -125a) in bone marrow mesenchymal stem cells (BMSCs) and RAW264.7 macrophages, we identified DP7-C/miR-124 as the optimal nanocomplex, demonstrating synergistic osteoimmunomodulatory effects. Results demonstrated that the DP7-C/miR-124 combination raised the expression of anti-inflammatory factors in inflammatory macrophages and decreased the expression of pro-inflammatory factors. It also stimulated the production of osteogenesis-related proteins BMP2 and Runx2 to promote BMSC osteogenesis. Mechanistic studies revealed bidirectional cellular crosstalk, where DP7-C/miR-124 enhanced IL-10-mediated anti-inflammatory macrophage polarization while reciprocally promoting BMSC differentiation through paracrine modulation. These findings establish DP7-C/miRNA nanocomplexes as next-generation osteoimmunomodulatory biomaterials that concurrently resolve inflammation and amplify bone regeneration through epigenetic-immune circuit regulation, offering a promising strategy for functionalized bone defect repair in inflammatory microenvironments.

Surface modification of titanium-based orthopedic implants has been investigated over the last decades to promote better bone-to-implant association, osseointegration, and fracture healing. Yet, post-surgical failure of coated orthopedic implants occurs due to poor adhesive strength, fatigue failure, high wear rate of coated materials, low biocompatibility, limited osseointegration, and stress-shielding effect. Therefore, there is an unmet clinical need to develop a smart coating strategy. Herein, we have created an electrospun nanofibrous coating for Ti-implants using piezoelectric Polyvinylidene fluoride (PVDF) polymer reinforced with osteoconductive nanofiller Zinc oxide (ZnO). We have found that by varying the ZnO content from 0.5 to 2.0 wt.% in the PVDF matrix, we can modulate the electrospun coating's mechanical, thermal, physicochemical stability, and piezoelectric characteristics. Our results proved that PVDF-ZnO nanofibrous coatings exhibit almost ~3-4 fold increase in the piezoelectric d₃₃ coefficient as well as output voltage, compared to pure PVDF using Piezo-responsive Force Microscopy (PFM). Furthermore, electrically poled piezoelectric PVDF-ZnO nanofibers also demonstrated a significant increment (~5-fold) in collagen deposition, hydroxyapatite formation, and improved bio- and hemo-compatibility compared to unpoled nanofibers. Furthermore, through the in vitro experiments, we have confirmed that the piezoelectric PVDF-ZnO nanofibrous activates calcium-calmodulin mediated cellular pathway to induce cell adhesion, proliferation, and cell spreading in the osteoblast cells. Nonetheless, using the biomimetic mechanical bioreactor, we have investigated the piezoelectricity-mediated increased focal adhesion and enhanced F-actin production under the physiologically relevant (i.e., 1%) mechanical strain in bone cells. Moreover, the current study elucidates the piezoelectric-based smart, multifunctional coating strategies for developing an osteoconductive implant.