Journal of biomedical materials research. Part A最新文献

Severe acute pancreatitis (SAP) is a prevalent gastrointestinal disease with no effective treatment to control inflammation currently. Macrophages, particularly peritoneal macrophages (PMOs), play a pivotal role in SAP inflammation by polarizing into M1 or M2 phenotypes, which exhibit distinct functional properties and cytokine expression profiles. Galectin-9 (Gal-9) modulates macrophage polarization, but its specific effect on PMOs in SAP remains unclear. In this study, hyaluronic acid-chitosan nanoparticles encapsulating Gal-9 (HA-CS-Gal-9 NPs) were developed for delivery. In vitro, HA-CS-Gal-9 NPs enhanced M2 marker expression and suppressed M1 markers in both naive (M0) and LPS-induced M1 macrophages. In vivo, HA-CS-Gal-9 NPs effectively delivered Gal-9, showing effective uptake by PMOs without notable toxicity, resulting in reduced IL-6, and increased IL-10 expression in PMOs. Treatment with these nanoparticles (NPs) decreased systemic pro-inflammatory cytokines, thereby alleviating pancreatitis severity. These findings demonstrate that Gal-9-loaded NPs robustly promoted M2 macrophage polarization, highlighting a promising therapeutic strategy for SAP.

The incorporation of robust meniscus-to-bone interfaces into tissue-engineered menisci is critical for their clinical translation. Generating gradients in collagen fiber organization and mineral content for tissue-engineered entheses is essential for achieving native tissue-like mechanics; however, engineering such gradients remains challenging. This study presents a tissue-engineered enthesis model consisting of a fibrochondrocyte-seeded cylinder of type I collagen gel with trabecular bone plugs on both ends. Using a tri-chamber bioreactor, spatially controlled biochemical (e.g., TGF-β1 and glucose) and biomechanical stimuli were applied, generating native-like collagen fiber structure and mechanics within tissue-engineered enthesis constructs. Confocal elastography revealed a more uniform local strain distribution and reduced peak strain in the enthesis constructs cultured in a tri-chamber bioreactor compared to those in a single chamber bioreactor, likely attributed to the enhanced collagen fiber organization. To further improve the integration at the collagen–bone plug interface, we introduced partially demineralized bone plugs to the constructs. Partial demineralization improved the mechanical performance of enthesis constructs, decreasing peak strain by > 30% and strain gradients by 50%, while increasing toughness and strain at failure by 50% and 40%, respectively. Overall, these findings highlight the importance of zone-specific biochemical and biomechanical stimuli and biomimetic scaffold materials to improve tissue-engineered implants.

Skin aging is marked by fibroblast decline and extracellular matrix (ECM) degradation, prompting the widespread use of poly-L-lactic acid (PLLA) dermal injectables for activating fibroblasts, stimulating neocollagenesis, and rejuvenating the skin. However, current PLLA formulations show variable efficacy and may trigger undesirable inflammatory responses. In this study, we compared two different PLLA formulations -one containing novel microspherical PLLA (PLLA-LASYNPRO) and the other containing a microflake-like PLLA -to assess their differing effects on human dermal fibroblasts and skin tissue. The results show that PLLA microspheres promote fibroblast migration, ECM synthesis, and wound contraction, while PLLA microflakes inhibit proliferation and elicit inflammatory gene expression. Transcriptomic profiling reveals that PLLA microspheres upregulate genes involved in fat cell differentiation and energy metabolism, with minimal immune activation. In contrast, PLLA microflakes trigger immune pathways and suppress regenerative signals. Importantly, each formulation induces unique long non-coding RNA (lncRNA) signatures, implicating lncRNAs in fibroblast-mediated skin remodeling. These findings highlight the novel design of PLLA microspheres as a critical determinant of their therapeutic outcome, offering a molecular basis for developing safer and more effective skin rejuvenation strategies.

Osteoporosis is an age-related bone disease closely associated with the accumulation of senescent cells in the bone marrow microenvironment, a pathological feature that is not fully addressed by current biomaterial-based therapies. Targeting cellular senescence and its associated inflammatory microenvironment presents a promising strategy for mitigating osteoporosis progression. Glycyrrhizic acid (GA), a naturally occurring triterpenoid, has been shown to alleviate cellular senescence in various age-related disorders. Herein, injectable GA/gelatin methacrylate hydrogel microspheres (GA@GelMA) were developed using microfluidic technology to enable sustained GA release. The microspheres demonstrated multiple functionalities in vitro, including suppression of cellular senescence, induction of M1-to-M2 macrophage polarization, and enhancement of osteogenic differentiation in bone marrow stem cells (BMSCs). In an ovariectomized (OVX) mouse model of osteoporosis, local administration of GA@GelMA microspheres significantly promoted bone formation and alleviated the senescence-associated inflammatory microenvironment. These GA@GelMA microspheres provide a multifunctional strategy integrating osteogenesis promotion and senescence modulation for the treatment of osteoporosis.

The neurovascular unit (NVU), including the blood–brain barrier (BBB), governs the interaction between neural tissue and blood vessels. The BBB is a highly selective interface that regulates molecular exchange between the bloodstream and the central nervous system. This study aimed to develop a structurally relevant, multicellular in vitro NVU model integrating both vascular and brain microenvironments to evaluate BBB function. A fibrous membrane mimicking the basement membrane was fabricated via electrospinning, while a methacrylated hyaluronic acid (MeHA)-collagen hydrogel was used on the brain side. Endothelial cells (ECs) were cultured on the vascular side, and astrocytes, pericytes, and neuronal model cells were embedded within the hydrogel. The model was optimized for cell viability and endothelial monolayer formation. Cell behavior was assessed via immunocytochemistry, and barrier function was evaluated using TEER measurements and permeability assays with fluorescein, 0.4 and 20 kDa dextran, ceftriaxone, and amikacin. CD31 expression was elevated in the multicellular model, indicating improved endothelial integrity. The model achieved a TEER of 166.86 ± 5.75 Ω versus 121.70 ± 13.58 Ω cm² in monoculture. Permeability to tracers was significantly reduced in the multicellular model, and ceftriaxone showed higher transport than amikacin, reflecting human BBB selectivity. This model provides a physiologically relevant platform for neurovascular research and drug screening.

Collagen-like proteins (CLPs) and their congeners can form stable triple helices but show limited fibril-forming ability, restricting their application as biomaterials. To more closely replicate the structural features of natural collagen, we engineered an extended CLP-CLP double domain (CLPdd) genetically encoded with Hydroxyproline (CLPdd-Hyp) and 3,4-dihydroxyphenylalanine (CLPdd-DOPA) using a genetic code expansion strategy. This study presents the first report of the dual incorporation of Hydroxyproline (Hyp) and 3,4-dihydroxyphenylalanine (DOPA) into the CLP double domain (CLPdd), yielding the variant CLPdd-HD, which exhibited significantly enhanced fibrillation, thermal stability, and biomaterial potential. Among the engineered variants, CLPdd-Hyp showed the most pronounced improvements in triple-helical structure, fibrillation behavior, wound healing efficacy, and cell adhesion highlighting its promise as a biomaterial. Biocompatibility assessments further confirmed the suitability of CLPdd variants for biomedical applications. Notably, CLPdd-HD demonstrated exceptional thermal stability and cell-adhesive properties, underscoring its potential for further optimization. This work lays a foundation for tailoring bacterial CLPs through strategic NCAA incorporation, opening new avenues for developing advanced collagen-mimetic biomaterials.

Manufacturers frequently use Ti-6Al-4V for permanently implanted medical devices. While clinically successful, Ti-6Al-4V corrodes at modular taper interfaces in both the hip and knee. Additionally, additive manufacturing (AM) can develop biomaterials with the potential to improve upon Ti-6Al-4V's properties. In this study, we used AM to generate Ti-Nb-Zr-Sn, comparing the admixture to classically melted Ti-Nb-Zr and wrought-annealed Ti-6Al-4V. We asked (1) how does manufacturing alter Ti-Nb-Zr biomaterial structure; (2) do resulting structural differences govern corrosion and semiconducting properties; and (3) does biomaterial chemistry and structure affect cell metabolic activity? To answer these questions, we first used scanning electron microscopy and electron backscattered diffraction to characterize microstructure. Then, we elucidated the corrosion properties and semiconducting performance in 0.1 M H₂O₂ and PBS solutions. Next, we measured the cell metabolic activity after 24 and 72 h. Manufacturing profoundly altered the Ti-Nb-Zr biomaterials, with AM processes generating a columnar microstructure consisting of elongated grains. This contrasted with the equiaxed β grains of the alloy produced by melting processes. However, these structural changes had little effect on the corrosion or semiconducting properties. Additionally, both Ti-Nb-Zr-Sn and Ti-Nb-Zr exhibited increased corrosion resistance and decreased defect densities over Ti-6Al-4V in 0.1 M H₂O₂. Finally, we documented superior cell metabolic properties on polished and as-built Ti-Nb-Zr-Sn surfaces after 72 h. Combined, these results suggest an inhibitory effect of ZrO₂ oxides on reactive oxygen species and support the continued characterization of Ti-Nb-Zr-Sn as a candidate biomaterial.

The combination of superior mechanical properties, corrosion resistance, and biological characteristics makes Ti-6Al-4V a widely used biomaterial. However, its clinical application as an orthopedic implant is limited by its hardness and weak osseointegration capacity. This study focuses on the development of a functionally graded biomaterial that has increased bioactivity and decreased mechanical mismatch with living tissue. In this scope, a novel radially functionally graded Ti-5Mo/hydroxyapatite (HA) biocomposite was successfully fabricated via pressure-assisted sintering using a specially designed mold that enabled directional HA enrichment toward the outer surface. This architectural design addresses the persistent challenge of combining mechanical reliability with biological functionality in load-bearing implants. Comprehensive characterization was performed, including x-ray diffraction (XRD), Rietveld refinement, optical and scanning electron microscopy (SEM/EDX), atomic force microscopy (AFM), contact angle measurements, and in vitro cytotoxicity assays using L929 fibroblast cells. Mechanical behavior was assessed through Brazilian splitting, three-point bending, microhardness, and tribological testing under both dry and corrosive conditions. The biocomposite exhibited a dual-phase α + β titanium matrix and HA-derived oxides in the surface layers, with a graded increase in porosity and hardness from the core to the periphery. Mechanical tests revealed a bending modulus of 22.4 GPa, close to that of cortical bone, while the surface showed enhanced roughness, hydrophilicity (contact angle 35.3°), and corrosion resistance. In vitro results confirmed the material's biocompatibility and superior cell viability in HA-rich regions. These findings demonstrate that the developed Ti-5Mo/HA FGM offers a structurally and biologically optimized solution for orthopedic and dental implant 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.