ACS Biomaterials Science & Engineering最新文献

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.

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.

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.

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.

Dimethylcurcumin (ASC-J9) is an organic active pharmaceutical ingredient with anti-inflammatory, antioxidant, and antitumor effects. However, its application has been significantly hindered by poor solubility in aqueous solutions, a short in vivo half-life, low bioavailability after oral administration, and limited accumulation and absorption in target areas. Nano-drug delivery systems can serve as drug carriers to enhance drug delivery, addressing these challenges with improved efficacy and reduced adverse effects. In this study, a microfluidic swirl mixer is used to prepare silk fibroin composite nanoparticles containing ASC-J9 and copper sulfate (CuS), and the effects of different process parameters on silk fibroin nanoparticles (SNPs) were explored and optimized. The synthesized composite ASC-J9-CuS@SNPs exhibited a mean particle diameter of 180 ± 10 nm and PDI of 0.20 ± 0.03. Two-dimensional/three-dimensional (2D/3D) cell experiments showed that the composite nanomaterials have excellent biocompatibility and antitumor activity with a noticeable cancer cell specificity. In vivo experiments showed that ASC-J9-CuS@SNPs effectively controlled tumor growth without causing damage to blood cells and vital organs. Both in vitro and in vivo experiments demonstrated that the anticancer effect was enhanced by photo thermotherapy. The current study provides a promising strategy for using silk fibroin as nanocarriers for breast cancer therapy.

IgA nephropathy (IgAN) is a primary glomerulonephritis mediated by autoimmunity, characterized by an abnormal increase and the deposition of IgA in the glomeruli. In recent years, most studies have emphasized the crucial role of the gut-kidney axis in the pathogenesis of IgA nephropathy, and the ileal Peyer patches in the intestinal mucosal immune system are the main site for IgA production. Therefore, in this study, hydroxychloroquine (HCQ) and dexamethasone (DXM) were used as model drugs, and yeast cell wall (YCW)-coated oleic acid-grafted chitosan (CSO) was used as a carrier to construct a yeast cell wall oral drug delivery system HCQ/DXM@CSO@YCW. This delivery system achieves ileal targeted delivery through the yeast cell wall (YCW), reduces IgA production, and synergistically regulates the inflammatory pathological environment. The delivery system had good gastrointestinal stability and biocompatibility. In vitro cell experiments had shown the targeted uptake ability of dendritic cells and macrophages, and in vitro intestinal experiments showed that the YCW has ileal targeting properties. In vivo pharmacodynamic experiments showed that the HCQ/DXM@CSO@YCW delivery system could significantly reduce the serum IgA levels and IgA deposition in the renal tissue of IgAN mice, as well as the levels of IL-6, TNF-α, and TGF-β in the renal tissue, improving the pathological morphology of the renal tissue. Therefore, the DXM/HCQ@CSO@YCW oral administration system provided a new intestinal targeted delivery platform for intestinal mucosal immunotherapy in IgA nephropathy.

Pathological fibrosis is a chronic disease, characterized by excessive extracellular matrix deposition, that remains a significant global health challenge. Despite its prevalence, current antifibrotic therapies are limited due to the complex interplay and signaling of profibrotic macrophages and fibroblast cells that underlies fibrotic tissue microenvironments. This study investigates a novel approach to combat fibrosis, harnessing the antifibrotic properties of the endogenous metabolite itaconate (IA) to target the pathological activation of the macrophage-fibroblast axis in fibrotic disease. To achieve therapeutic delivery relevant to the chronic nature of fibrotic conditions, we incorporated IA into the backbone of biodegradable polyester polymers, poly(dodecyl itaconate) (poly[IA-DoD]), capable of long-term localized release of IA. Degradation characterization of poly(IA-DoD) revealed that IA, as well as water-soluble IA-containing oligomeric groups, is released in a sustained manner. Treatment of murine bone marrow-derived macrophages and human dermal fibroblasts demonstrated that the degradation products of poly(IA-DoD) effectively modulated profibrotic behavior. Macrophages exposed to the degradation products exhibited reduced profibrotic responses, while fibroblasts showed decreased proliferation and myofibroblast α-smooth muscle actin expression. These findings suggest that poly(IA-DoD) has the potential to disrupt the fibrotic cycle by targeting key cellular players. This polymer-based delivery system offers a promising strategy for the treatment of fibrotic diseases.