ACS Biomaterials Science & Engineering最新文献

In recent years, a major focus in the field of tissue engineering has been the search for a suitable biomaterial for clinical applications. Researchers have sought to optimize natural, synthetic, and hybrid options, with an aim to enhance biological, chemical, physical, and mechanical properties. In the past decade, silk fibroin has emerged as a promising approach due to its suitable properties. Specifically, the chemical modification of silk fibroin with methacrylate agents, namely glycidyl methacrylate, methacrylic anhydride, and gelatin methacryloyl, confers the material with improved biophysical properties. This review presents an in-depth overview of silk fibroin's structure and suitable properties, silk fibroin methacrylate synthesis and characterization techniques, and applications of silk fibroin in bone and cartilage, skin, and nerve tissue engineering. Challenges include a limited understanding of methacrylate agents on specific cell types, which can be addressed by further in vivo investigations utilizing biomaterial compounds to confer tissue-specific needs. We conclude with our perspective of the present limitations and future trends of the methacrylated SF platform.

Collagen, a protein known for its long lifespan, is susceptible to accumulation of advanced glycation end products (AGEs) with age. These AGEs are considered markers that indicate the aging severity and influence the mechanics of tissues, leading to fragile bones and hardened skin. While many cross-linking AGEs have been widely studied for their ability to reduce the elasticity of biological tissues, contributing to skin hardening and fragile bones, through strong covalent bonds, non-cross-linking AGEs, or AGE adducts, are typically investigated as indicators of aging or as signaling factors in pathological conditions. However, recent experimental findings have revealed that the number of AGE adducts in aged bone is comparable to enzymatic cross-links, which are significantly more abundant than cross-linking AGEs. Based on these observations, we consider one of the most abundant AGE adducts - carboxymethyllysine (CML) - and employ molecular dynamics simulations to explore its direct impact on the mechanical and conformational properties of single tropocollagen molecules. Our models demonstrate that tropocollagen peptides, constructed based on sequences experimentally identified with sites of CML modifications in type I collagen derived from human cortical bone, exhibit heterogeneous behaviors under tensile testing. Still, most of these modified peptides display compromised structural stability, reduction in structural strength, and diminished energy dissipation ability when tension is applied. This study highlights the potential impact of non-cross-linking AGEs on collagen behavior at molecular scale and provides insights into the mechanisms underlying these modifications. Gaining a deeper understanding of the role of AGE adducts and their contribution to the aging process may pave the way for future solutions in antiaging research.

Real-time in vivo imaging of bacterial infections is an important goal to aid the study and treatment of bacterial infections. Phages can be genetically engineered to ensure a particular biomolecular target specificity, and gold nanomaterials can be conjugated to phages for a variety of applications including biosensing. In this paper, we describe methods to use phage-gold nanorod conjugates for in vivo detection and imaging of the bacterial species Pseudomonas aeruginosa in mice. The imaging modalities are computed tomography (CT), using gold as a contrast agent, and fluorescence, which can be applied when the FDA-approved near-infrared (NIR) dye indocyanine green (ICG) is also chemically cross-linked to the bioconjugates. In addition, rapid protocols for validating bioconjugate synthesis and the initial assessment of toxicity are given. In this example, the phage-gold nanorod probe is shown to specifically highlight P. aeruginosa without cross-reactivity to another Gram-negative organism (V. cholerae) in vivo and appears to be biocompatible. Phage-directed imaging probes may thus be useful for the characterization and diagnosis of bacterial infections.

The biomechanical similarity of magnesium to cortical bone, along with its biocompatibility and biodegradability, makes it promising for orthopedic implants. However, rapid degradation compromises the structural integrity and fixation, causing failure. To address this issue, we developed a hard-soft dual-state coating to regulate degradation and improve performance. A dense magnesium hydroxide hard coating was formed by sodium hydroxide treatment, and the hydrogel soft coating formed by freeze-drying was 44.5 μm thick. The dual coating significantly improved the corrosion resistance and mechanical properties. Mg-OH-Hy implants exhibited a reduced corrosion rate of 0.61 mm/year (±0.02), an ultimate fracture force of 750 N (±10), and a pullout force of 350 N (±10). Electrochemical testing revealed an E_corr of -1.08 V and an I_corr of 10^-3·8 mA/cm². This dual coating approach improves mechanical stability, controls degradation, and promotes bone integration, providing personalized solutions for diverse clinical applications.

Prostate cancer is the second most common cancer among men globally. In this study, we developed a prostate-cancer-targeted gold nanoparticle-based photothermal and photodynamic complex (GNR-ICG-FA@PSMA) to enhance the targeting efficiency of prostate cancer cells and simultaneously deliver photothermal therapy (PTT) and photodynamic therapy (PDT). For the in vitro tests, ROS assays, annexin V/PI staining, and MTT assays were conducted. In the in vivo tests, fluorescence and photoacoustic imaging systems were used to track the distribution of nanoparticles in animal models. Tumor tissues were analyzed post-treatment using Triphenyl tetrazolium chloride (TTC) staining, Hematoxylin and Eosin (HE) staining, and Immunohistochemistry (IHC) staining. The in vitro results showed that GNR-ICG with laser irradiation produced high levels of ROS, the highest rate of apoptosis, and the lowest cell viability. In the in vivo tests, tail-injected GNR-ICG-FA@PSMA reached the tumor within 9 h. During laser irradiation, GNRs increased the temperature (<50 °C), inducing necrosis, while ICGs generated ROS, leading to apoptosis. The results demonstrated that folic acid (FA) and PSMA antibodies improved prostate cancer-specific targeting. GNRs and ICGs contributed to the photothermal and photodynamic effects, respectively. This study confirms the potential of GNR-ICG-FA@PSMA for targeted photothermal and photodynamic therapy of prostate cancer.

The therapeutic potential of silk fibroin (SF) and hyaluronic acid (HA) composite hydrogels for corneal epithelial wound healing was assessed, focusing on the molecular weight of SF related to outcomes. Initially, SF of varying molecular weights was analyzed, and a medium molecular weight (M-SF; 10-72 kDa, average 40 kDa) was identified as most effective in promoting cell proliferation, attachment, and migration in various assays. A hydrogel formulation, H-SF/HA gel@M-SF, was then developed by incorporating M-SF (10-72 kDa, average 40 kDa) into a base hydrogel composed of high molecular weight SF (H-SF; 18-100 kDa, average 60 kDa) and HA. The physicochemical properties of the hydrogels, including pH balance, extensibility, and swelling rate, were characterized. The biological functions of the hydrogels were evaluated by using human corneal epithelial (HCE-T) cells and a mouse corneal injury model. H-SF/HA gel@M-SF exhibited supported enhanced expression of key genes associated with corneal repair, such as NOTCH I, GSK3β, ACTG, and VCL when compared with a serum-free medium. In vivo studies using mice demonstrated that H-SF/HA gel@M-SF achieved complete wound closure within 48 h, outperforming the H-SF/HA gel. These results underscore the significance of the SF molecular weight and concentration in hydrogel design and highlight the potential of H-SF/HA gel@M-SF for ophthalmic applications.

Bone tissue damage and associated disorders significantly compromise the quality of life of affected patients, and existing therapeutic options remain limited. Bone marrow mesenchymal stem cells (BMSCs) play a crucial role in bone regenerative medicine, owing to their ability to differentiate into osteoblasts. Utilizing cutting-edge technologies, nanomaterials, and bioactive compounds can emulate the natural bone tissue microenvironment, offer a three-dimensional scaffold that facilitates the osteogenic differentiation of BMSCs, and modulate signals at the molecular level, thereby showing promise for applications in bone regeneration and repair. This review seeks to discuss the latest research advancements, elucidate the underlying mechanisms, and highlight the potential benefits of these technologies in augmenting the osteogenic capacity of BMSCs. Furthermore, the challenges and future directions for integrating these technologies in practical settings are discussed to pioneer new vistas in bone regenerative medicine.

Nanoparticles have emerged as promising drug carriers owing to their ability to permeate cell membranes and enhance drug stability. However, their clinical application faces significant challenges, including rapid diffusion, inefficient retention at target sites, and burst drug release. This study proposes the use of adhesive nanoparticles derived from acrylated bioengineered mussel adhesive proteins (MAPs). Acrylic groups were conjugated to lysine residues in MAPs to form polyacrylate-MAPs by photo-cross-linking, retaining sufficient 3,4-dihydroxyphenylalanine residues for strong tissue adhesion in aqueous environments. These nanoparticles were designed to adhere effectively to the administration sites and facilitate continuous drug release. In vitro and in vivo evaluations demonstrated that the acrylated MAP-based nanoparticles exhibited superior wet adhesive properties, sustained drug release, and long-term retention at the administration site and effectively suppressed tumor growth, ensuring that a single dose maintained a therapeutic concentration at the target site over extended periods. Thus, this approach could address the challenges of drug localization and retention, significantly improving therapeutic efficacy. This study emphasizes the versatility of bioengineered MAP-based adhesive nanoparticles for locoregional and sustained drug delivery, with promising applications in cancer therapy, regenerative medicine, and other biomedical fields.

Noninvasive cancer imaging significantly improves diagnostics by providing comprehensive structural and functional information about tumors. Herein, we explored palladium nanoparticles loaded hafnium-based metal-organic framework (MOF) (Hf-EDB), i.e., Pd@Hf-EDB as an efficient dual modal contrast agent for computed tomography (CT) and photoacoustic imaging (PAI). The synergistic collaborations between (i) high-Z element Hf-based MOF with superior X-rays absorbing capabilities, (ii) H₂EDB linkers with special π-donation and π-acceptor characteristics capable of strongly anchoring noble metals, and (iii) Pd nanoparticles with broad absorption in the UV to near-infrared (NIR) regions due to strong interband transition are ideal for implementation in CT and PAI. The successful synthesis of Pd@Hf-EDB nanoparticles was confirmed through morphology, crystallinity, and compositional characterizations using X-ray diffraction, SEM, TEM, DLS, and EDS. Soft X-ray tomography verified cellular uptake via phagocytosis of Pd@Hf-EDB by BxPC-3 tumor cells. In-vitro experiments revealed superior CT imaging performance of Pd@Hf-EDB over traditional molecular contrast agents like Iohexol. Broad absorption range in the UV-vis/NIR regions and superior PAI capabilities of Pd@Hf-EDB relative to gold nanorods are reported. Furthermore, the in vivo xenograft model demonstrated significant contrast enhancements near the tumor, highlighting the excellent PAI and CT capabilities of the synthesized Pd@Hf-EDB.

Bone defects pose a global concern due to their high prevalence. Despite the significant advances in the development of novel therapies and sustainable biomaterial solutions, these still do not perfectly address the clinical needs, in particular, the paradigm shift of personalized treatments. In this sense, marine-origin materials allied to three-dimensional (3D) printing are arising as a feasible alternative to develop innovative personalized approaches, namely, bone tissue engineering (TE). In this study, novel 3D-printed scaffolds composed of collagen obtained from the maricultured marine sponge Chondrosia reniformis and calcium phosphates extracted from codfish (Gadus morhua) bones doped with strontium, and combined with alginate, were developed as a promising approach for bone regeneration. The 3D-printed scaffolds demonstrated suitable pore size and porosity and high interconnectivity, with adequate mechanical properties for bone TE. The in vitro assays conducted with a human osteosarcoma cell line (Saos-2 cells) cultured onto the 3D-printed scaffolds demonstrated a notable improvement in both cell viability and proliferation up to 14 days of culturing. This enhancement was particularly evident in the case of 3D-printed scaffolds containing Sr-doped calcium phosphates. Aligned with the principles of the blue economy and within a sustainable development approach, an innovative 3D-printed scaffold produced from sustainable marine-derived collagen and strontium-doped calcium phosphates with adequate mechanical properties, architecture, and encouraging in vitro performance was developed for bone tissue engineering scaffolding applications.