ACS Biomaterials Science & Engineering最新文献

In the context of regenerative medicine, the design of scaffolds to possess excellent osteogenesis and appropriate mechanical properties has gained significant attention in bone tissue engineering. In this review, we categorized materials into metallic, inorganic, nonmetallic, organic polymer, and composite materials. This review provides a more integrated and multidimensional analysis of scaffold design for bone tissue engineering. Unlike previous works that often focus on single aspects, such as material type or fabrication technique, our review takes a broader approach. It analyzes the interaction between scaffold materials, 3D printing techniques, scaffold structural designs, modification methods, porosities, and pore sizes, and the composition of materials (particularly composite materials). Meanwhile, it focuses on their impacts on scaffolds' osteogenic potential and mechanical performance. This review also provides suggested ranges for porosity and pore size for different materials and outlines recommended surface modification methods. This approach not only consolidates current knowledge but also highlights the interdependencies among various factors affecting scaffold efficacy, offering deeper insights into optimization strategies tailored for specific clinical conditions. Furthermore, we introduce recent advancements in innovative 3D printing techniques and novel composite materials, which are rarely addressed in previous reviews, thereby providing a forward-looking perspective that informs future research directions and clinical applications.

This study provides a bibliometric and bibliographic review of emerging applications of micro- and nanotechnology in treating ocular diseases, with a primary focus on glaucoma. We aim to identify key research trends and analyze advancements in devices and drug delivery systems for ocular treatments. The methodology involved analyzing 385 documents indexed on the Web of Science using tools such as VOSviewer and Bibliometrix. The results show a marked increase in scientific output, highlighting prominent authors and institutions, with England leading in the field. Key findings suggest that nanotechnology holds the potential to address the limitations of conventional treatments, including low ocular bioavailability and adverse side effects. Nanoparticles, nanovesicles, and polymer-based systems appear promising for prolonged and controlled drug release, potentially offering enhanced therapeutic efficacy. In conclusion, micro- and nanotechnology could transform ocular disease treatment, although challenges remain concerning the biocompatibility and scalability of these devices. Further clinical studies are necessary to establish these innovations within the therapeutic context of ophthalmology.

Osteoarthritis (OA) is a chronic multifactorial disease characterized by cartilage degeneration, pain, and reduced mobility. Current therapies primarily aim to relieve pain and restore function, but they often have limited effectiveness and side effects. Coixol, a bioactive compound from Coix lacryma-jobi L., exhibits anti-inflammatory and analgesic properties, suggesting potential benefits in OA treatment. This study explored the effects of coixol on OA chondrocytes. Primary chondrocytes from OA rats were isolated and treated with varying concentrations of coixol. Cell viability and proliferation were assessed by using CCK-8 assays. The expression of genes related to ferroptosis and autophagy was analyzed through RT-qPCR, Western blot, and immunofluorescence. Moreover, the study investigated the characteristics and performance of coixol-loaded PDLLA-PEG-PDLLA (PLEL)/gelatin sponge (GS) hydrogels (Coixol@PLEL/GS) for enhancing osteochondral defect repair by specifically targeting chondrocyte ferroptosis and autophagy. The characteristics of coixol-loaded PDLLA-PEG-PDLLA/gelatin sponge (Coixol@PLEL/GS) hydrogels were evaluated using cryo-scanning electron microscopy (SEM) or SEM, and coixol release kinetics were determined. In vivo, a rat osteochondral defect model was used to assess the efficacy of Coixol@PLEL/GS in osteochondral defect repair using International Cartilage Repair Society (ICRS) scores, Safranin O/Fast green staining, Toluidine blue staining, and immunofluorescence. Coixol significantly increased the viability and proliferation of OA chondrocytes in a dose-dependent manner. Furthermore, coixol inhibited ferroptosis and stimulated autophagy, as evidenced by the upregulation of related genes. In vivo, Coixol@PLEL/GS remarkably enhanced the repair of osteochondral defects compared to that of control groups. In conclusion, coixol protects OA chondrocytes by improving survival, inhibiting ferroptosis, and activating autophagy, highlighting its potential as a therapeutic strategy for OA treatment.

Mechanical properties of engineered connective tissues are critical for their success, yet modern sensors that measure physical qualities of tissues for quality control are invasive and destructive. The goal of this work was to develop a noncontact, nondestructive method to measure mechanical attributes of engineered skin substitutes during production without disturbing the sterile culture packaging. We optimized a digital holographic vibrometry (DHV) system to measure the mechanical behavior of Apligraf living cellular skin substitute through the clear packaging in multiple conditions: resting on solid agar as when the tissue is shipped, on liquid media in which it is grown, and freely suspended in air as occurs when the media is removed for feeding. We utilized full-field measurement to assess the complete surface deformation pattern to compare with vibration theory and found the patterns observed in air showed the closest behavior to theory. To simulate the effects of the actual culture dish geometry and the trilayer composition of the tissue on the porous membrane support, we employed finite element (FE) analysis. To simulate changes in thickness and stiffness that may occur with manufacturing process variations, we dried samples over time and observed measurable increases in the fundamental mode frequency which could be predicted by altering the thickness of the tissue layers in the FE model. However, quantitative estimates of the engineered tissue stiffness based on vibration theory are unrealistically high due to the signal being dominated by the stiff underlying membrane on which the tissue is cultured. Thus, although DHV is not able to specifically quantify the thickness or modulus or identify small spot defects, it has the potential to be used assess the overall properties of a tissue in-line and noninvasively for quality control.

The development of stable and standardized in vitro cytotoxicity testing models is essential for drug discovery and personalized medicine. Microfluidic technologies, recognized for their small size, reduced reagent consumption, and control over experimental variables, have gained considerable attention. However, challenges associated with external pumps, particularly inconsistencies between individual pumping systems, have limited the real-world application of cancer-on-a-chip technology. This study introduces a novel triplicate cell culture system (Tri-CS) that simultaneously supports dynamic cultures in three independent units using a single peristaltic pump, ensuring consistent flow conditions. Our findings demonstrate that the Tri-CS significantly reduces variability compared to individual pump systems, enhancing the reliability of anticancer drug cytotoxicity testing. Furthermore, we evaluated gemcitabine cytotoxicity, which shows enhanced drug efficacy in dynamic conditions. Fluorescein diffusion tests revealed greater diffusion efficiency in dynamic cultures, which contributed to the higher observed drug efficacy. The potential for broader application of the Tri-CS, including its compatibility with commercially available transwells and the opportunity for use in more complex cancer-on-chip models, positions this system as a valuable tool for advancing microphysiological systems in preclinical research.

Restenosis remains a long-standing limitation to effectively maintain functional blood flow after percutaneous transluminal angioplasty (PTA). While the use of drug-coated balloons (DCBs) containing antiproliferative drugs has improved patient outcomes, limited tissue transfer and poor therapeutic targeting capabilities contribute to off-target cytotoxicity, precluding adequate endothelial repair. In this work, a DCB system was designed and tested to achieve defined arterial delivery of an antirestenosis therapeutic candidate, cadherin-2 (N-cadherin) mimetic peptides (NCad), shown to selectively inhibit smooth muscle cell migration in vitro and limit intimal thickening in early animal PTA models. To enable successful tissue transfer in the current work, a nanoparticle excipient system previously demonstrated to be an effective carrier of NCad in vitro was integrated with customized DCB coating methodologies designed to prevent therapeutic loss during delivery. DCB design took into consideration four components: (1) the angioplasty balloon; (2) a poly(ethylene oxide) (PEO) monolayer acting as a hydrophilic spacer between the balloon surface and the nanoparticles to assist with improved nanoparticle release; (3) surface-modified degradable polar hydrophobic ionic polyurethane (D-PHI) nanoparticles loaded with NCad to facilitate the transport of the therapeutic peptide into vascular tissue; and (4) a PEO sacrificial coating applied over the nanoparticle excipient layer to prevent premature losses during transit to the artery. The nanoparticle-DCB platform successfully delivered NCad to rat carotid tissue, with superior efficacy and increased permeation within the vessel wall compared with soluble NCad infusion alone. Nanoscale technologies in conjunction with enhanced DCB design properties hold promise in advancing the localized delivery of preventive restenosis therapies in vascular disease.

Mineralized biological tissues rich in type I collagen (e.g., bone and dentin) exhibit complex anisotropic suprafibrillar organizations in which the organic and inorganic moieties are intimately coassembled over several length scales. Above a critical size, a defect in such tissue cannot be self-repaired. Biomimetic materials with a composition and microstructure similar to that of bone have been shown to favorably influence bone regeneration. This highlights the value of developing a similar formulation in an injectable form to enable minimally invasive techniques. Here, we report on the fabrication and application potential of an injectable collagen/CHA (carbonated hydroxyapatite) cell-free hydrogel. The organic part consists of spray-dried nondenatured and dense collagen microparticles, while the inorganic part consists of biomimetic apatite mineral. By mixing both powders at desired tissue-like ratios with an aqueous solvent in one step, spontaneous co-self-assembly occurs, leading to the formation of a mineralized matrix with suprafibrillar tissue-like features thanks to the induced liquid crystalline properties of collagen on one hand and apatite on the other hand. When injected into soft tissue, the mineralized collagen hydrogel free of chemical cross-linking agents exhibits suitable cohesion and is biocompatible. Preliminary in vitro tests in a tooth cavity model show its integration onto dentin with a biomimetic interface. Based on the results, this versatile injectable mineralized collagen hydrogel shows promising potential as a biomaterial for bone tissue repair and mineralized tissue-like ink for bioprinting applications.

Poly(ethylene glycol) diacrylate (PEGDA) hydrogels are biocompatible and photo-cross-linkable, with accessible values of elastic modulus ranging from kPa to MPa, leading to their wide use in biomedical and soft material applications. However, PEGDA gels possess complex microstructures, limiting the use of standard polymer theories to describe them. As a result, we lack a foundational understanding of how to relate their composition, processing, and mechanical properties. To address this need, we use a data-driven approach to develop an empirical predictive framework based on high-quality data obtained from uniaxial compression tests and validated using prior data found in the literature. The developed framework accurately predicts the hydrogel shear modulus and the strain-stiffening coefficient using only synthesis parameters, such as the molecular weight and initial concentration of PEGDA, as inputs. These results provide simple and reliable experimental guidelines for precisely controlling both the low-strain and high-strain mechanical responses of PEGDA hydrogels, thereby facilitating their design for various applications.

Sufficient vascular system and adequate blood perfusion is crucial for ensuring nutrient and oxygen supply within biomaterials. Actively exploring the optimal physical properties of biomaterials in various application scenarios has provided clues for enhancing vascularization within materials, leading to improved outcomes in tissue engineering and clinical translation. Here we focus on reviewing the physical properties of biomaterials, including pore structure, surface topography, and stiffness, and their effects on promoting vascularization. This angiogenic capability has the potential to provide better standardized research models and personalized treatment strategies for bone regeneration, wound healing, islet transplantation and cardiac repair.

Tooth loss is a prevalent problem faced by individuals of all ages across the globe. Various biomaterials, such as metals, bioceramics, polymers, composites of ceramics and polymers, etc., have been used for the manufacturing of dental implants. The success of a dental implant primarily depends on its osseointegration rate. The current surface modification techniques fail to imbibe the basics of tooth development, which can impart better mineralization and osseointegration. This can be improved by developing an understanding of the developmental pathways of dental tissue. Stimulating the correct signaling pathways through inductive material systems can bring about a paradigm shift in dental implant materials. The current review focuses on the developmental pathway and mineralization process that happen during tooth formation and how surface modifications can help in biomimetic mineralization, thereby enhancing osseointegration. We further describe the effect of dental implant surface modifications on mineralization, osteoinduction, and osseointegration; both in vitro and in vivo. The review will help us to understand the natural process of teeth development and mineralization and how the surface properties of dental implants can be further improved to mimic teeth development, in turn increasing osseointegration.