ACS Biomaterials Science & Engineering最新文献

The skeletal system exhibits remarkable mechanical properties, serving as the primary supportive framework in vertebrates. Dysregulation of bone metabolic activity can alter bone quality and quantity, leading to skeletal deformity, pain, or disease. Accurate assessment, therefore, necessitates robust methods capable of evaluating both mechanical competence and structural characteristics across various scales. Numerous bone assessment techniques have been developed to comprehensively assess these parameters ex vivo and increasingly in situ. We discuss a spectrum of modalities, including mechanical testing, radiological imaging, microscopic, and spectroscopic analysis, evaluating their operational principles, applications in understanding bone health and pathophysiology, inherent advantages, and current limitations. Notably, we also highlight how a synergistic combination of two or more techniques provides information exceeding the capabilities of individual methods alone and hence advance our understanding for future diagnostic avenues. Integration of artificial intelligence (AI) further holds considerable potential to augment the analytical prowess of these methods, offering enhanced insights for decision-making. By elucidating these robust methodologies, we aim to expand the understanding of bone health and disease, with implications for improved patient management and treatment strategies. This review consolidates a spectrum of interconnected bone assessment techniques, each offering unique insights and collectively enabling diverse modalities for opportunistic screening of skeletal disorders in an aging global population.

Gastrointestinal (GI) wounds remain a major clinical challenge due to the difficulty of achieving effective hemostasis and sustained mucosal repair after endoscopic procedures. Here, we developed a photo-cross-linkable, nanoparticle-reinforced Gelatin Methacryloyl (GelMA) hydrogel for endoscopic application under blue-light activation. The incorporation of nanoparticles─particularly kaolinite─enhanced the injectability, structural integrity, and resistance to enzymatic degradation of GelMA while preserving excellent biocompatibility. Upon illumination, the precursor rapidly cross-linked into a uniform, adhesive hydrogel layer that conformed tightly to irregular wound surfaces. The composite hydrogel exhibited efficient hemostatic activity and cytocompatibility, supporting early epithelial regeneration. In vivo studies using rat skin wounds and a porcine gastric ulcer model demonstrated that the kaolinite-modified GelMA hydrogel accelerated wound closure and improved mucosal restoration compared to pristine GelMA. Overall, this light-activated, mechanically robust GelMA composite provides a precisely injectable and biologically active platform for the endoscopic management of gastrointestinal lesions, offering a practical approach for rapid sealing, bleeding control, and tissue repair in minimally invasive settings.

Type 1 diabetes mellitus (T1D) is a global disease, and stem cell-derived insulin-producing cells show great promise for treatment; their in vitro development is limited. This suggests that the in vivo environment, particularly the native extracellular matrix (ECM), plays a crucial role in cell maturation. To address this, our study investigated this challenge through a two-part investigation aimed at enhancing the functional maturity of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs). In the first part, we optimized a differentiation protocol by selectively identifying key small molecules. We found that a combination of CHIR98014 and Latrunculin A was crucial for improving the efficiency at different stages of differentiation. Based on this, in the second part of our study, we examined a novel approach combining an ultralow attachment-based 3D culture (ULA 3D) with a pancreas-specific decellularized ECM (pdECM) derived from porcine pancreas. We aimed to determine if this combination could enhance the differentiation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) into functional insulin-producing cells. The study compared the differentiation across four groups: a standard 2D culture, ULA 3D culture, a pdECM-supported 2D culture, and the combined pdECM-supported 3D culture. We found that the definitive endoderm and pancreatic progenitor marker expression was significantly higher in the ULA group, especially when supported by the pdECM. Pancreatic endocrine gene and protein expressions, including PDX1, NGN3, and INS, were notably enhanced in this combined 3D cultured group. Crucially, the pdECM-supported 3D culture group showed higher levels of glucose-stimulated insulin secretion, confirming the functional maturity of the differentiated cells. This study demonstrates that creating and integrating a tissue-specific pdECM into a 3D culture system provides a more physiologically relevant microenvironment, significantly improving the differentiation and function of WJ-MSCs and holding great potential for effective regenerative therapies for T1D.

Oxidative damage is induced by reactive oxygen species, which leads to protein denaturation and subsequently triggers various diseases. Antioxidant peptides represent an effective approach for treating oxidative damage. In this study, a non-natural peptide library with antioxidant properties was designed. The effective antioxidant peptide CVAGVA was isolated from the peptide library through chromatographic and mass spectrometry analyses. The Fukui index and various chemical evaluation results indicated that CVAGVA was a more efficient antioxidant peptide. Experiments using a cell oxidative damage model confirmed that this peptide can effectively scavenge reactive oxygen species within cells and mitigate the damage effect. This article established models of sunburn, liver injury, keratitis, burns, etc. in mice. The results demonstrated that CVAGVA increased the treatment and recovery rate of sunburn by approximately 20% and enhanced the treatment effect of carbon tetrachloride-induced liver injury by approximately 16.7%. It can safeguard collagen in skin tissue and reduce the inflammatory response during long-term ultraviolet exposure. Regarding keratitis prevention, the recovery effect of CVAGVA was approximately 15% higher than that of glutathione. When CVAGVA was loaded onto zinc alginate hydrogel for burn treatment, the therapeutic effect was approximately 33.3% higher compared to the treatment without CVAGVA. These experiments have verified that the synthesized non-natural antioxidant peptides exhibit excellent antioxidant performance.

Needle-free transdermal vaccination is an attractive alternative to hypodermic injection but its use remains limited because of the poor skin permeability of macromolecular antigens. Here, we integrated chemical penetration enhancers (CPEs) into solid-in-oil (S/O) dispersions to improve transdermal delivery and vaccine efficacy. The 24 different CPEs spanning five chemical classes were screened in fluorescein isothiocyanate-ovalbumin permeation assays using excised mouse skin. Fatty acids produced the strongest effects, with decanoic acid and linoleic acid yielding >3-fold increases in permeation, whereas long-chain aldehydes and alcohols showed negligible or modest activity. A random-forest model trained on CPE physicochemical descriptors identified the pK_a value as the dominant determinant of enhancement, motivating evaluation of pH-responsive alkylamines. Alkylamine-loaded S/O formulations achieved permeation comparable to fatty acids, and decanoic acid, linoleic acid, and decylamine were selected for further study. FT-IR analysis of stratum corneum sheets after treatment with isopropyl myristate loaded with decanoic acid, linoleic acid, or decylamine indicated that there was increased lipid fluidity consistent with CPE insertion into the intercellular lipid matrix. In vivo, CPE-containing formulations caused only transient increases in transepidermal water loss and no histological damage, indicating acceptable skin tolerability. Notably, S/O patches containing decylamine or linoleic acid elicited antiovalbumin IgG titers in mice comparable to subcutaneous injection. These findings establish CPE-loaded S/O dispersions as a promising platform for safe, needle-free transdermal vaccination.

Polyetheretherketone (PEEK) is a semicrystalline synthetic polymer commonly used in orthopedic devices because of its chemical stability, thermal elasticity, radiopacity, and mechanical moduli similar to that of bone. However, its inherent biological inertness results in poor initial fixation and insufficient bone bonding, which can compromise implant stability and long-term success. To overcome this limitation, various surface modification strategies, such as physical treatments (for example, sandblasting or sulfonation) and coating deposition of titanium or hydroxyapatite, have been explored. However, physical modification makes it difficult to control surface roughness uniformity, and coatings risk generating wear debris in vivo, which may inhibit surrounding bone formation and cause bone resorption. To address these challenges, PEEK was modified via plasma-enhanced chemical vapor deposition using CH₄/N₂ gas to deposit a uniform carbonaceous thin film containing amine groups, and its osteogenic effects and underlying mechanisms were investigated. Plasma-treated PEEK demonstrates enhanced hydrophilicity and cell adhesion without altering surface roughness and promotes osteoblastic differentiation compared to untreated PEEK in vitro. Analysis of the mechanisms promoting osteoblastic differentiation using RNA sequencing revealed the activation of FAK signaling associated with cell adhesion and the independent upregulation of the BMP4/Smad signaling pathway. In vivo implantation into rat femurs demonstrated that untreated PEEK exhibited fibrous tissue intervention at the PEEK–bone interface, whereas plasma-treated PEEK showed bone formation without fibrous tissue intervention as early as 2 weeks postoperatively. Moreover, at 6 weeks postimplantation, plasma-treated PEEK exhibited superior quality bone formation compared to untreated PEEK. These findings suggest that plasma treatment effectively enhances the osteogenic potential of PEEK, addressing its inherent biological inertness and highlighting its potential as a next-generation biomaterial for orthopedic implants.

Polymeric microbubbles (MBs) are increasingly being explored as contrast agents for ultrasound (US) imaging and as carriers for US-mediated therapies. Many of these applications benefit from MBs that exhibit strong nonlinear acoustic responses and robust cavitation capabilities. Although structural features, such as size, are known to influence the overall acoustic behavior of MBs, their specific impact on nonlinear responses and cavitation dynamics remains poorly understood and characterized. In this study, we investigated the size-dependent acoustic properties of poly(butyl cyanoacrylate) (PBCA) MBs. Our results show that larger PBCA MBs produce stronger acoustic signals and more pronounced nonlinear responses, including second harmonic generation, whereas smaller PBCA MBs exhibit greater acoustic stability and a higher capacity to sustain stable cavitation. These findings elucidate the role of size in shaping the acoustic behavior of polymeric MBs in a quantitative manner and may inform the design of new agents for enhanced US imaging and US-mediated therapies.

Allergic reactions trigger the release of histamine (HA) by immune cells when the body encounters allergens, such as pollen, dust, or certain foods. Besides its role in immune responses, HA also functions as a neurotransmitter released by neurons in the brain. The enzyme diamine oxidase (DAO) is mainly responsible for breaking down HA and deficiency in DAO can lead to histamine intolerance, known as enteral histaminosis, where the inability to metabolize histamine results in its accumulation, potentially causing allergic reactions, anaphylaxis, vertigo, Tourette syndrome, and other issues. To address this, there is a growing need for point-of-care (PoC) detection technologies capable of fast, accurate, and sensitive on-site HA detection. In this study, we developed a sensor by integrating Nb₂CT_x MXene with tungsten trioxide (WO₃) using silane linkage by 3-aminopropyl triethoxysilane (APTES), resulting in WO₃-APTES-Nb₂CT_x composite which was used as the electrode modifier on a flexible carbon yarn (CY) electrode. The density functional theory (DFT) analysis was employed to investigate the interaction of HA with WO₃-APTES-Nb₂CT_x and Nb₂CT_x and electron transport sites, providing a deeper understanding of the sensing mechanism. The sensing capability of the developed sensor was evaluated electrochemically, and the sensor demonstrated exceptional performance, including an ultralow detection limit of 432.4 pM with a broad detection range between 1 nM and 100 nM, as well as high selectivity for HA over other interfering molecules. The sensor performance is tested with human serum, sweat, and cerebrospinal fluid, highlighting its relevance for both physiological and clinical use. Moreover, the sensor successfully detected HA released from subcultured SH-SY5Y neuronal cells. Lastly, we developed a prototype named “HistoTrack” by repurposing a used pregnancy test kit into a disposable electrochemical sensor for on-site HA detection, paving a new way for plastic waste repurposing. This innovative, highly sensitive, and selective sensor marks a significant advancement in inflammation monitoring and offers great potential for broader medical and research applications.

Bone fractures often involve both bone and muscle damage, representing a critical need for regenerative strategies that can repair both tissues. We developed a gelatin-based hydrogel system with tunable stiffness to guide spheroids formed from induced pluripotent stem cell (iPSC)-derived mesenchymal stromal cells (iMSCs) for simultaneous muscle and bone repair. Hydrogels were formed using hydrogen peroxide with horseradish peroxidase as a catalyst and substrate stiffness ranged from 1.6 to 9.3 kPa. Hydrogels entrapping iMSC spheroids enabled localized release of the iMSC secretome that exhibited biological effects. iMSC spheroids in soft hydrogels enhanced myogenic differentiation of C2C12 myoblasts via paracrine signaling. Conversely, iMSC spheroids exposed to the myoblast secretome and cultured in stiffer hydrogels exhibited enhanced osteogenic differentiation. This study demonstrates the synergistic influence of stiffness and reciprocal secretome signaling on iMSC behavior, offering a clinically relevant “two-in-one” platform for musculoskeletal regeneration.