ACS Biomaterials Science & Engineering最新文献

Radiofrequency (RF) tissue welding is an innovative tissue anastomosis technique that utilizes bioimpedance to convert electrical energy into thermal energy, enabling the connection and reconstruction of tissues via the denaturation and crosslinking of proteins. However, the high temperatures generated in this process often lead to excessive thermal damage to tissues, thereby adversely impacting cellular activity and impeding tissue repair in practical applications. In this study, we developed a polyacrylamide/alginate (PAAm/Alg) hydrogel with high ionic conductivity (16.8 ± 1.2 S/m) achieved by introducing Ca²⁺ for the purpose of reducing thermal damage in RF tissue welding. The PAAm/Alg-Ca²⁺_0.5M hydrogel possessed excellent mechanical properties with a stress of 315.6 ± 14.1 kPa and an elongation of 382.7 ± 89.0%. Additionally, the hydrogel exhibited a high water content (83.7 ± 0.3%) and excellent stability of swelling property in water. In addition, the hydrogel extract showed good biocompatibility with no significant adverse effects on cell activity in the cytotoxicity test. At last, we conducted ex vivo experiments to investigate the effectiveness of the hydrogel as a cooling agent during RF tissue welding. The result showed that the maximum temperature was effectively reduced from 137.9 ± 4.7 to 101.8 ± 2.5 °C, while the strength of the anastomotic stoma (12.0 ± 3.2 kPa) was not affected by the intervention of this hydrogel. Histological analysis also revealed that the anastomotic structure of the tissue with hydrogel intervention was more intact than that of the control. Thus, the PAAm/Alg-Ca²⁺_0.5M hydrogel has been demonstrated to function effectively as a cooling agent, offering a new strategy for thermal damage control in RF tissue welding.

The rising incidence of bacterial infections poses a significant challenge to global public health. The development of safe and effective antibacterial treatment strategies is an urgent need in the field of biomedicine. In this work, we developed a smart nanoparticle-hydrogel platform to address bacterial infections in wounds. Rifampicin-loaded chitosan-functionalized nanoparticles (R-CNP) could break bacterial barriers and enhance antibiotic internalization. R-CNP reduced the minimum inhibitory concentration of rifampicin against Staphylococcus aureus and greatly enhanced the bactericidal effect of rifampicin. Furthermore, R-CNP was incorporated into thermosensitive hydrogels (HG) to construct HG(R-CNP) for enhanced antibiotic accumulation and wound protection. In the mouse model with a bacterial-infected wound, treatment with R-CNP reduced the bacterial content by 98.5% as compared to treatment with free rifampicin. Therefore, this smart nanoparticle-hydrogel platform constructed by FDA-approved or natural polymers, offers significant therapeutic efficacy on bacterial-infected wounds, showing great promise for clinical translation.

Nanofiber (NF) membranes have demonstrated considerable potential in cellular transmigration studies due to their resemblance to the biophysical properties of basement membranes, enabling cellular behaviors that closely mimic those observed in vivo. Despite their advantages, conventional NF membranes often encounter issues in transmigration assays due to their transparency, which leads to overlapping fluorescent signals from transmigrated and nontransmigrated cells. This overlap complicates the clear differentiation between these cell populations, making the quantitative evaluation of live-cell transmigration challenging. To address this issue, we developed a light-blocking nanofiber (LB-NF) membrane by incorporating carbon black into polycaprolactone NFs. This LB-NF membrane is designed not only to mimic the biophysical properties of the basement membrane but also to enable in situ analysis of transmigrated cells through its light-blocking properties. Our study demonstrated the effectiveness of the LB-NF membrane in a transmigration assay using human brain cerebral microvascular endothelial cells (HBEC-5i), enabling physiologically relevant cell transmigration while significantly enhancing the accuracy of in situ fluorescence detection. Furthermore, drug testing within a choroidal neovascularization model using the LB-NF membrane underscores its utility and potential impact on pharmaceutical development, particularly for diseases involving abnormal cell transmigration. Therefore, the developed LB-NF membrane represents a valuable tool for the precise assessment of in situ cellular transmigration and holds significant promise for advancing drug screening and therapeutic development.

The advancement of in vitro engineered cardiac tissue-based patches is paramount for providing viable solutions for restoring cardiac function through in vivo implantation. Numerous techniques described in the literature aim to provide diverse mechanical and topographical cues simultaneously, fostering enhanced in vitro cardiac maturation and functionality. Among these, cellulose paper-based scaffolds have gained attention owing to their inherent benefits, such as biocompatibility and ease of chemical and physical modification. This study introduces a novel approach of utilizing customized paper-based scaffolds as cell culture substrates, facilitating both the formation and manipulation of cell constructs while promoting mechanical contraction. Here, we investigated two methodologies to foster mechanical contractions of paper-based constructs: the incorporation of micropatterns on paper to dictate cell orientation and macropattern created by the origami-folded paper. Both approaches provide mechanical support and foster cardiac functionality. However, while micropatterning does not significantly improve the functional parameters, a macropattern created by origami folding proves to be essential in facilitating contraction of the paper-based cardiac constructs. Furthermore, we provide proof of principle for the combination with a layer of physiologically differentiated microvascular networks. This approach holds great promise for the development of structurally organized contractile cardiac tissues with the possibility of creating multistrata of cardiac and vascular layers to promote in vivo cell survival and function beyond what is typically achieved in conventional cell culture.

Engineered skeletal muscle tissues are critical tools for disease modeling, drug screening, and regenerative medicine, but are limited by insufficient maturation. Because innervation is a critical regulator of skeletal muscle development and regeneration in vivo, motor neurons are hypothesized to improve the maturity of engineered skeletal muscle tissues. However, the impact of motor neurons on muscle phenotype when added prior to the onset of muscle differentiation is not clearly established. In this study, benchtop fabrication equipment was used to facilely fabricate chambers for engineering three-dimensional (3D) skeletal muscles bundles and measuring their contractile performance. Primary chick myoblasts were embedded in an extracellular matrix hydrogel solution and differentiated into engineered muscle bundles, with or without the addition of human induced pluripotent stem cell (hiPSC)-derived motor neurons. Muscle bundles differentiated with motor neurons had neurites distributed throughout their volume and a higher myogenic index compared to muscle bundles without motor neurons. Innervated muscle bundles also generated significantly higher twitch and tetanus forces in response to electrical field stimulation after 1 and 2 weeks of differentiation compared to noninnervated muscle bundles cultured with or without neurotrophic factors. Noninnervated muscle bundles also experienced a decline in rise and fall times as the culture progressed, whereas innervated muscle bundles and noninnervated muscle bundles with neurotrophic factors maintained more consistent rise and fall times. Innervated muscle bundles also expressed the highest levels of the genes for slow myosin light chain 3 (MYL3) and myoglobin (MB), which are associated with slow twitch fibers. These data suggest that motor neuron innervation enhances the structural and functional development of engineered skeletal muscle constructs and maintains them in a more oxidative phenotype.

Adipose-derived stem cells (ADSCs) are known to promote angiogenesis and adipogenesis. However, their limited ability to efficiently target and integrate into specific tissues poses a major challenge for ADSC-based therapies. In this study, we identified a seven-amino acid peptide sequence (P7) with high specificity for ADSCs using phage display technology. P7 was then covalently conjugated to decellularized adipose-derived matrix (DAM), creating an “ADSC homing device” designed to recruit ADSCs both in vitro and in vivo. The P7-conjugated DAM significantly enhanced ADSC adhesion and proliferation in vitro. After being implanted into rat subcutaneous tissue, immunofluorescence staining after 14 days revealed that P7-conjugated DAM recruited a greater number of ADSCs, promoting angiogenesis and adipogenesis in the surrounding tissue. Moreover, CD206 immunostaining at 14 days indicated that P7-conjugated DAM facilitated the polarization of macrophages to the M2 phenotype at the implantation site. These findings demonstrate that the P7 peptide has a high affinity for ADSCs, and its conjugation with DAM significantly improves ADSC recruitment in vivo. This approach holds great potential for a wide range of applications in material surface modification.

Bone defects, whether caused by trauma, cancer, infectious diseases, or surgery, can significantly impair people’s quality of life. Although autografts are the gold standard for treating bone defects, they often fall short in adequately forming bone tissue. The field of bone tissue engineering has made strides in using scaffolds with various biomaterials, stem cells, and growth factors to enhance bone healing. However, some biological structures do not yield satisfactory therapeutic outcomes for new bone formation. Recent studies have shed light on the crucial role of immunomodulation, specifically the interaction between the implanted scaffold and host immune systems, in bone regeneration. Immune cells, particularly macrophages, are pivotal in the inflammatory response, angiogenesis, and osteogenesis. This review delves into the immune system’s mechanism toward foreign bodies and the recent advancements in scaffolds’ physical and biological properties that foster bone regeneration by modulating macrophage polarization to an anti-inflammatory phenotype and enhancing the osteoimmune microenvironment.

Ischemic heart disease morbidity and mortality ensue as the ventricle remodels, and cardiac function is lost following myocardial infarction. Previous studies have shown that applying a biodegradable, elastic epicardial patch onto the ischemic cardiac wall preserves the cardiac function and alters the remodeling process. In this report, the capacity to deliver a recombinant adeno-associated virus (AAV) encoding human vascular endothelial growth factor (VEGF) was evaluated to determine if it would provide benefit beyond a patch alone. Coaxial electrospinning of a poly(ether ester urethane) urea generated microfibrous patches with fibers loaded in their core with VEGF-AAV in poly(ethylene oxide) or vehicle alone. In a rat infarction model, epicardial patches were placed 3 days post-infarction. Over an 8 week period following the intervention, end-diastolic area was lower and ejection fraction greater in the patch-VEGF group compared with the control patch and sham surgery groups. There was also a greater number of α-SMA-positive cells, blood vessels, and positive immunostaining for VEGF in the patch-VEGF group compared with groups having patches lacking VEGF. The approach of combining mechanical (patch) and biofunctional (controlled release angiogenic therapy) support through a scaffold-based gene vector transfer approach may be an effective option for dealing with the adverse ventricular wall remodeling that leads to end-stage cardiomyopathy.

Due to the intense demand for low-cost, environmentally friendly, and stable uric acid (UA) detection methods, a novel biosensing nanosystem made with marine diatom was studied. Reduced by live diatom (Thalassiosira pseudonana), metallic nanoparticles (Cu_X) were hybridized with the heteronanostructure (Diatom frustule, DF), showing peroxidase activity 2.66-fold over horseradish peroxidase (HRP). To immobilize the enzyme directionally with increasing loading amounts, silaffin peptides (R₅ and T₈) were designed for tagging the urate oxidase (UoX). The enzyme loading on DF of tagged UoX was 1.76-fold (R₅) and 1.54-fold (T₈) that of untagged UoX. The activity of immobilized UoX-R₅ was 5.29–11.76-fold more than that of free UoX-R₅ at various pH levels (5–10) and temperatures (20–60 °C). The nanosystem (UoX-R₅ immobilized on Cu_X-coated diatom frustules, termed as BioHNS) demonstrated a superior linear range of 5 × 10^–6 to 1 × 10^–3 M and a detection limit of 1.6 μM, surpassing the performance of the majority of reported UA sensors. The recoveries of UA in urine were detected by the BioHNS, ranging from 96.93 to 105.35%, with a relative deviation of less than 5.00%. The BioHNS showed excellent anti-interference and storage stability (2 months). In summary, BioHNS demonstrates significant potential as a sustainable and environmentally friendly biosensor for uric acid detection, highlighting its substantial relevance to the biomedical applications of marine diatoms.

Traditional cancer research has long relied on two-dimensional (2D) cell cultures, which inadequately mimic the complex three-dimensional (3D) microenvironments of in vivo tumors. Recent advancements in 3D cell cultures, particularly cancer spheroids, have highlighted their superior physiological relevance. However, existing methods for spheroid generation often require complex, multistep fabrication processes that limit scalability and reproducibility. In this study, we present a novel single-step photolithographic technique to fabricate high-aspect-ratio V-slanted hydrogel microwells. By employing polyethylene glycol (PEG)-based hydrogels, we create biocompatible, extracellular matrix (ECM)-like scaffolds that enhance gas and nutrient exchange while promoting uniform spheroid formation. The hydrogel microwells allow precise control of spheroid size, achieving a physiologically relevant diameter of 425 μm within 12–24 h, and the resulting spheroids exhibiting high viability over 3 weeks. Moreover, the method facilitates the creation of scalable multiwell arrays for high-throughput applications, making it suitable for both small-scale and large-scale experimental needs. This platform addresses the limitations of traditional microwell fabrication, offering a robust, efficient, and reproducible system for generating physiologically relevant 3D models with valuable applications in cancer research, drug testing, and tissue engineering.