Journal of biomedical materials research. Part A最新文献

Vascular graft infection is a rare but life-threatening condition, primarily occurring after 30 days post-surgery. Meta-analysis has shown that antimicrobial coatings on graft materials do not prevent these infections. Moreover, infections still occurs even though studies have shown that there is no bacterial proliferation or bacterial penetration of common vascular graft material. The time frame of infection, meta-analysis, and in situ studies suggest that bacteria present at the suture site are introduced into the surrounding tissue or that systemically circulating bacteria may be surviving, proliferating, diffusing slowly, and evading host immune defense in synthetic vascular grafts. De novo vascular graft materials, such as tissue-engineered vascular graft material and decellularized vasculature may provide an in situ platform for studying survival, proliferation, and diffusion in tissue and tissue-like materials. In this study, we used confocal microscopy to image the penetration depth of bacteria over time as a proxy for the diffusion of Staphylococcus aureus and Escherichia coli into alginate, GelMA, and decellularized porcine vascular tissue. We quantified viable bacteria breakthrough as a function of biomaterial type. We found that the penetration depth over time was similar in all three biomaterials, however E. coli broke through much less from tissue than from engineered materials, while S. aureus had higher breakthrough in the GelMa but otherwise equal rates. These results point to the possibility of interstitial growth control relative to surface coatings as a future target for engineering infection resistance in engineered vascular grafts.

Bone tissue regeneration for large defects presents a significant challenge, demanding scaffolds that combine robust mechanical support alongside a bioactive environment. Hydrogels represent a promising solution for bone regeneration due to their biocompatibility, tunable properties, and crosslinked three-dimensional (3D) networks mimicking the natural extracellular matrix (ECM). However, their mechanical properties remain suboptimal for restoring bone defects effectively. This study introduces a novel bilayer laminate scaffold, integrating a biostable fiber-reinforced composite (FRC) with a biodegradable, 3D-printed hyaluronic acid (HA)-based hydrogel. To enhance bioactivity, bioactive glass (BAG) was incorporated into the hydrogel layer. Comprehensive characterization confirmed the scaffold's chemical and morphological properties, as well as its controlled degradation, sustained ion release, and bioactivity. Additionally, the study revealed that the BAG-induced alkaline pH shift (up to 9.24) affected hydrazone crosslinking efficiency, resulting in reduced hydrogel stiffness (86 ± 8 Pa versus 150 ± 4 Pa in control). The system showed excellent cytocompatibility, supporting high viability and proliferation of human bone marrow stem cells (BMSCs) embedded within the hydrogel component. The developed scaffolds promoted osteogenic differentiation, as evidenced by increased ALP activity and upregulated expression of osteogenic marker genes. Nevertheless, BAG incorporation did not enhance early osteogenic differentiation compared to control scaffolds. In conclusion, this bilayer scaffold offers a promising platform for bone tissue engineering (TE), providing some insights into the chemical interplay between inorganic fillers and hydrogel matrix for optimizing future scaffold designs.

Biomaterial-based skeletal muscle tissue engineering approaches have largely focused on mimicking the 3D aligned architecture of native muscle, which is critical for guiding myotube formation and force transmission. In contrast, fewer studies incorporate glycosaminoglycan (GAG)-mediated biochemical cues despite their known role in regulating myogenesis and growth factor sequestration. In this study, we develop aligned collagen-GAG (CG) scaffolds using directional freeze-drying and systematically vary GAG type by incorporating GAGs of increasing sulfation levels (hyaluronic acid, chondroitin sulfate, and heparin). While all scaffold variants support myoblast adhesion, metabolic activity, and myotube alignment, heparin-modified CG scaffolds significantly enhance myoblast metabolic activity and myogenic differentiation as measured by myosin heavy chain (MHC) expression and myotube size. We additionally show that heparin-modified scaffolds sequester and retain significantly higher levels of insulin-like growth factor-1 (IGF-1), a potent promoter of myogenesis, compared to other scaffold groups. Together, these results highlight the importance of tailoring GAG type in CG scaffolds for targeted applications and underscore the promise of heparin-modified CG scaffolds as a material platform for skeletal muscle tissue engineering.

Glioblastoma is the most common primary malignant brain tumor with a 5-year survival rate < 5%. The standard of care involves surgical resection followed by treatment with the alkylating agent temozolomide (TMZ). GBM cells that evade surgery eventually become resistant to TMZ and lead to recurrence of tumors in patients. With only four drugs currently FDA-approved for GBM treatment, there is a need for a clinically relevant model capable of accelerating the identification of new therapies. Microgels are microscale (~10–1000 μm) hydrogel particles that can be used to encapsulate cells in a tailorable 3D matrix. Microdroplets offer short diffusion lengths relative to conventional hydrogel constructs (> 1 mm) to limit spatial distributions of hypoxia and potentially screen therapeutics in a controlled and physiologically relevant environment. Here, we establish a method to encapsulate GBM cells in gelatin and polyethylene glycol (PEG) microgels. We show that microgel composition can affect cell morphology and further, that collections of GBM-laden hydrogels can be used to quantify the effect of single versus metronomic doses of TMZ. GBM metabolic activity is maintained in microgel culture and GBM cells display drug response kinetics similar to previously established literature using macro-scale hydrogel constructs. Finally, we show microgels can be integrated with a liquid handler to enable high-throughput screening using cell-laden microgels.

Postoperative infections remain a major complication after spinal fusion surgery, often caused by biofilm-forming bacteria that resist short-term antibiotic prophylaxis. Vancomycin (VAN) is sometimes delivered locally during surgery; however, levels diminish rapidly, leaving patients vulnerable to late-onset infections. We developed a composite hydrogel integrating perfluorohexane-based emulsions within alginate or fibrin matrices to enable both sustained and ultrasound-triggered VAN release. Water-in-oil-in-water emulsions were prepared using fluorosurfactant-stabilized perfluorohexane as the volatile oil phase, then embedded in hydrogels and exposed to ultrasound (2.5 MHz, 5.5 MPa peak negative pressure) to initiate acoustic droplet vaporization for triggered release. Drug release was quantified spectrophotometrically and with fluorescent-labeled VAN, while antibacterial efficacy was tested against Staphylococcus aureus. Hydrogels directly loaded with free VAN exhibited burst release (~55%–67% within 24 h) followed by limited sustained release, which is suboptimal for prolonged coverage. In contrast, emulsion-loaded hydrogels reduced premature leakage, retaining > 70% VAN on Day 1 and providing gradual baseline release. Ultrasound application enhanced VAN release up to 8.75-fold in alginate and 27.5-fold in fibrin hydrogels after 7 days (p < 0.0001), supporting both continuous and on-demand delivery. Only alginate-emulsion hydrogels showed measurable antibacterial activity, as drug-matrix interactions in fibrin prevented release; ultrasound-treated samples displayed significantly greater efficacy over 7 days (p < 0.05 vs. no ultrasound). This dual-mode delivery platform enables spatial and temporal control of VAN release, combining early prophylaxis with ultrasound-triggered reinforcement, and holds promise for improving infection prevention in orthopedic surgeries by aligning drug delivery with clinical timelines.