Biomaterials Science最新文献

Chronic wounds (CWs) are a significant public health concern and affect 1-2% of the world's population. They are responsible for high morbidity and mortality rates. Bacterial infections caused by Staphylococcus aureus and Pseudomonas aeruginosa are very common in CWs and prevent normal wound healing steps from taking place. Carbon nanofibers (CNFs) have attracted interest due to their inherent antibacterial and blood clotting abilities, as well as mechanical strength. The aim of this research was to engineer coaxial fibers by wet-spinning as new platforms for drug delivery in CW care (promoting rapid blood clotting and consequent tissue regeneration). Coaxial fibers were produced with an outer layer (shell) made of a mechanically resilient polycaprolactone (PCL at 10 wt%) reinforced with carbon nanofibers (CNFs at 50, 100, and 150 μg mL^-1), while the inner layer (core) was made of a highly hydrated mixture of 2 wt% sodium alginate (SA) loaded with ceftazidime (CZ) at 128 μg mL^-1 (minimum bactericidal concentration). The fibers' double-layer structure was verified by scanning electron microscopy. Core-shell fibers were deemed highly flexible and mechanically resilient and resistant to rupture, with such properties being improved with the incorporation of CNFs. Most fibers preserved their structural integrity after 28 days of incubation in physiological-like medium. Furthermore, data reported the ability of CZ combined with CNFs to fight microbial proliferation and showed that the presence of CNFs promoted blood clotting, with PCL/CNFs50 being the most effective from the group. It was found that higher concentrations of CNFs had a detrimental effect, highlighting a concentration-dependent response. The presence of PLC in the fibers resulted in a mitigation of the CNFs' cytotoxic impact on keratinocytes. The incorporation of CZ had no effect on the metabolic activity of the cells. Overall, the results demonstrated the potentialities of the engineered coaxial fibers for applications in wound care.

Correction for 'Biomimetic proteoglycan nanoparticles for growth factor immobilization and delivery' by Nooshin Zandi et al., Biomater. Sci., 2020, 8, 1127-1136, https://doi.org/10.1039/C9BM00668K.

Unleashing T cell function is critical for efficacious cancer immunotherapy. Here, we present an in vivo T cell activation strategy by silencing Casitas B-lineage lymphoma proto-oncogene b (Cbl-b), an intracellular checkpoint, to effectively combat solid tumors. The polymersomes are able to efficiently load and deliver siRNA against cblb to T cells both in vitro and in vivo, successfully silencing the cblb gene expression in primary T cells and enhancing the IL-2 receptor CD25 expression, which in turn enhances T cell function and prevents T cell exhaustion. In vitro and in vivo studies showed that siRNA against cblb caused an effective inhibition of tumor progression in subcutaneous B16-F10 and LLC models, in which a significant increase of effector T cells in peripheral blood mononuclear cells and an increase of effector T cells and a significant decrease of Treg cells in the tumor were clearly observed. This polymersome-mediated down-regulation of the cblb gene in T cells provides a promising approach for activating T cells and enhancing their anti-tumor capacity.

The gut-liver axis plays a crucial role in maintaining metabolic balance and overall human health. It orchestrates various processes, such as blood flow, nutrient transfer, metabolite processing, and immune cell communication between the two organs. Traditional methods, such as animal models and two-dimensional (2D) cell cultures, are insufficient in fully replicating the intricate functions of the gut-liver axis. The emergence of microfluidic technology has revolutionized this field, facilitating the development of organ-on-a-chip (OOC) systems. These systems are capable of mimicking the complex structures and dynamic environments of the gut and liver in vitro and incorporating sensors for real-time monitoring. In this article, we review the latest progress in gut-on-a-chip (GOC) and liver-on-a-chip (LOC) systems, as well as the integrated gut-liver-on-a-chip (GLOC) models. Our focus lies in the simulation of physiological parameters, three-dimensional (3D) structural mimicry, microbiome integration, and multicellular co-culture. All these aspects are essential for constructing accurate in vitro models of the gut and liver. Furthermore, we explore the current applications of OOC technology in the study of the gut and liver, including its use in disease modeling, toxicity testing, and drug screening. Finally, we discuss the challenges that remain and outline potential future directions for advancing GOC and LOC development in vitro.

Bone tissue engineering aims to address critical-sized defects by developing biomimetic scaffolds that promote repair and regeneration. This study introduces a material extrusion-based embedded bioprinting approach to fabricate dense cellular constructs within methacrylated hyaluronic acid (MeHA) hydrogels enhanced with bioactive microparticles. Composite matrices containing human bone allograft or tricalcium phosphate (TCP) particles were evaluated for their rheological, mechanical, and osteoinductive properties. High cell viability (>95%) and uniform strand dimensions were achieved across all bioprinting conditions, demonstrating the method's ability to preserve cellular integrity and structural fidelity. The inclusion of bone or TCP particles did not significantly alter the viscosity, crosslinking kinetics, or compressive modulus of the MeHA hydrogels, ensuring robust mechanical stability and shape retention. However, bone allograft particles significantly enhanced osteogenic differentiation of human mesenchymal stem cells (hMSCs), as evidenced by increased alkaline phosphatase (ALP) activity and calcium deposition. Notably, osteogenesis was observed even in basal media, with a dose-dependent response to bone particle concentration, highlighting the intrinsic bioactivity of allograft particles. This study demonstrates the potential of combining embedded bioprinting with bioactive matrices to create dense, osteoinductive cellular constructs. The ability to induce osteogenesis without external growth factors positions this platform as a scalable and clinically relevant solution for bone repair and regeneration.

Extracellular vesicles (EVs) are small membrane-bound sacs released by cells that play crucial roles in intercellular communication. They transport biomolecules between cells and have both diagnostic and therapeutic potential. Artificial EVs, designed to mimic natural EVs, have been developed using various methods. In this study, Lactobacillus plantarum was used to create Lactobacillus-derived artificial EVs (LAEs) for skin rejuvenation and anti-aging. LAEs demonstrated monodispersity and effectively improved adverse gene expression and wound healing in fibroblasts. They also modulated aging-related genes and improved skin conditions in humans. Their simplicity, promptness, and lack of animal-derived sources make LAEs a promising alternative to natural EVs. LAEs have the potential to overcome the technical limitations of artificial EVs and advance EVs or exosome-based technologies for comprehensive skin rejuvenation.

Chronic wounds remain in a state of disrupted healing, impeding neurite outgrowth from injured nerves and poor development of new blood vessels by angiogenesis. Current therapeutic approaches primarily focus on the restoration of vascularization and overlook the need of nerve regeneration for complete healing. Vascular endothelial growth factor (VEGF) is a critical growth factor supporting angiogenesis in wound healing, promoting vascularization and has also demonstrated neuro-protective capabilities in both central and peripheral nervous system. While the delivery of pro-regenerative recombinant growth factors has shown promise, gene delivery offers greater stability, reduced off-target side effects, diminished cytotoxicity, and lower production costs. In this context, the overarching goal of this study was to develop a VEGF-activated scaffold with the potential to provide a multifaceted response that enhances both angiogenesis and nerve repair in wound healing through the localized delivery of plasmid encoding VEGF (pVEGF) encapsulated within the GET peptide system. Initially, delivery of pVEGF/GET nanoparticles to dermal fibroblasts led to higher VEGF protein expression without a compromise in cell viability. Transfection of dermal fibroblasts and endothelial cells on the VEGF-activated scaffolds resulted in enhanced VEGF expression, improved endothelial cell migration and organization into vascular-like structures. Finally, the VEGF-activated scaffolds consistently displayed enhanced neurogenic ability through improved neurite outgrowth from neural cells in in vitro and ex vivo models. Taken together, the VEGF-activated scaffold demonstrates multifaceted outcomes through the induction of pro-angiogenic and neurogenic responses from dermal, vascular and neural cells, illustrating the potential of this platform for the healing of chronic wounds.

Critically-sized bone defects that cannot spontaneously heal on their own remain a significant problem in the clinic. Synthetic polymeric implants are promising therapies for improving bone healing as they are highly tunable and avoid the potential complications associated with autologous bone grafts. However, biostable implants such as poly(methyl methacrylate) (PMMA) suffer from numerous shortcomings including negligible biodegradability and limited osseointegration with bone. Hydrolytically-degradable polymeric implants such as poly(caprolactone) (PCL) or poly(lactic-co-glycolic acid) (PLGA) have shown promise facilitating bone growth before being resorbed, but matching the degradation rate of these polyesters with the rate of bone regeneration continues to be an engineering challenge. To address these limitations with current synthetic bone implant materials, cell-degradable polymer/hydroxyapatite composites were developed as in situ-curing bone substitutes. The polymeric component was formulated from a thioketal (TK) dithiol linker and a tri-functional epoxy to facilitate rapid crosslinking upon deployment. To enable biologically-responsive implant resorption, the TK unit is specifically cleaved by cell-produced reactive oxygen species (ROS). TK bone substitutes possessed tunable curing and mechanical properties, were selectively degraded in dose-dependent concentrations of ROS, were non-cytotoxic, and demonstrated significantly greater bone regeneration capacity than PMMA in a critically-sized rat skull defect model. These combined results highlight the therapeutic potential of cell-degradable bone void fillers compared against conventional polymeric bone implants.

Parkinson's disease is a neurodegenerative condition associated with the progressive loss of dopaminergic neurons. This leads to neurological impairments with heightening severity and is globally increasing in prevalence due to population ageing. Cell transplantation has demonstrated significant promise in altering the disease course in the clinic, and stem cell-derived grafts are being investigated. Current clinical protocols involve systemic immunosuppression to prevent graft rejection, which could potentially be avoided by encapsulating the therapeutic cells in a locally immunosuppressive biomaterial matrix before delivery. Here we report the progression of an immunomodulatory encapsulation system employing ultrapure alginate hydrogel beads alongside tacrolimus-loaded microparticles in the encapsulation of dopaminergic neuron progenitors derived from human induced pluripotent stem cells (hiPSCs). The hiPSC-derived progenitors were characterised and displayed robust viability after encapsulation within alginate beads, producing dopamine as they matured in vitro. The encapsulation system effectively reduced T cell activation (3-fold) and protected progenitors from cytotoxicity in vitro. The alginate bead diameter was optimised using microfluidics to yield spherical and monodisperse hydrogels with a median size of 215.6 ± 0.5 μm, suitable for delivery to the brain through a surgical cannula. This technology has the potential to advance cell transplantation by locally protecting grafts from the host immune system.

Interactions between cells and the extracellular matrix (ECM) alter cellular behaviors, including adhesion, migration, proliferation, and differentiation via focal adhesions that link the ECM to the actin cytoskeleton as an intracellular signaling pathway. Although nanomaterials with various mechanical, geometrical, and topographical features have been used to provide a variety of cell-ECM interactions, it remains unclear how their nanostructured surfaces affect cellular behavior. In this study, we investigated focal adhesion dynamics during the migration and proliferation of HeLa cells on silica bead (SB) arrays with various nanotopographies. Cell adhesion was altered according to the surface curvature and pinhole size of the SB arrays, and cell morphology was determined by the ratio of the adhesive and non-adhesive areas of cells on the SB arrays. In turn, this triggered different focal adhesion dynamics in cells. In addition, we demonstrated the rapid migration and high proliferation characteristics of rounded cells with weak adhesion based on confocal microscopy analysis and migration trajectory on SB arrays, indicating focal adhesion dynamics-mediated cell migration and proliferation on nanostructured surfaces.