ACS Biomaterials Science & Engineering最新文献

Current limitations in engineered tissues arise from the inability to provide sufficient nutrients to cells deep within constructs, restricting their viability. This study focuses on enhancing diffusion by creating a microporous microenvironment using gelatin microparticles within collagen scaffolds. By leveraging the FRESH (Freeform Reversible Embedding of Suspended Hydrogels) 3D bioprinting technique, gelatin microparticles are utilized both as a support material and as a thermoresponsive porogen to establish interconnected pores. The results indicate that scaffolds with 75% porosity significantly increase diffusion rates and cell viability, extending beyond the conventional ∼200 μm limit. Additionally, integrating vascular-like channels with porous scaffolds and applying perfusion improved nutrient transport, leading to enhanced cell survival in larger constructs. This combination of microporosity and perfusion represents a promising approach to create thicker tissues without necrotic regions, potentially paving the way for scalable tissue engineering applications. The findings suggest that optimizing pore sizes and scaffold perfusion can bridge the gap between rapid tissue formation and slower vascularization processes, enabling the future development of functional tissue constructs at clinically relevant scales.

Tuberculosis (TB) is a severe respiratory infectious disease caused by Mycobacterium tuberculosis (M.tb), which puts enormous pressure on public health and economic systems worldwide. Therefore, accurate diagnosis and timely intervention of TB are critical for interrupting disease transmission and reducing mortality among TB patients. However, the low bioavailability, inadequate targeting, and significant adverse side effects of conventional antibiotics and the emergence of the multidrug-resistant M.tb strain result in limited TB treatment efficacy or even the development of multidrug-resistant TB. The development of nanomaterials provides new perspectives to improve the drawbacks of antibiotics for improved TB treatment, while enabling the diagnosis of TB. Herein, we review the conventional and nanotechnology-based diagnosis and intervention strategy of TB and the currently developed novel methods to solve the TB dilemma.

In the domain of tissue engineering and regenerative medicine, artificial replacements have been developed as viable options for esophageal reconstruction and serve as alternatives to traditional surgical procedures. Restoration of smooth muscle functionality is crucial in esophageal regeneration. We evaluated the efficacy of esophageal reconstructions in an animal model, using tissue-engineered films with a leaf-stacked structure (FLSS), seeded with mesenchymal stem cells (MSCs), which were genetically modified with myogenic genes. Esophageal partial defects were variously reconstructed in animals (n = 8 per group, except the no-implantation group), categorized as (1) normal rats; (2) rats implanted with naked FLSS; (3) rats implanted with FLSS with MSCs; (4) rats implanted using FLSS with myogenesis-inducing gene transfected MSCs; and (5) rats without implantation at the defect site (n = 3). The FLSS exhibited appropriate mechanical characteristics for transplantation. Successful repair of esophageal defects was observed with significantly enhanced epithelial regeneration in the MSC-seeded FLSS group compared to that in the naked FLSS group. Moreover, smooth muscle regeneration was notably higher in the FLSS with myogenesis-inducing gene transfected MSCs than in the group without myogenic gene transfection. The myogenesis-inducing gene-transfected MSC-seeded FLSS group showed a tendency toward increased smooth muscle regeneration, this indicates that FLSS with myogenesis-inducing genes transfected MSC may contribute positively to the maintenance of function in the reconstructed esophagus.

Efficient therapeutic approaches for bone regeneration are urgently required to address the significant challenges associated with the repair of large-scale or long-segment bone defects. Peptide-functionalized hydrogels (PFHs) have emerged as important bioactive materials in bone tissue engineering because they produce biomimetic microenvironments enriched with multiple biochemical signals. This review summarizes the key fabrication techniques for PFHs and discusses their diverse applications in different fields. Furthermore, we systematically highlighted the biochemical functionalization of PFHs, which includes basic functions such as cell adhesion, cell recruitment, and osteoinduction; improved functions such as angiogenesis, biomineralization, immune regulation, and hormone regulation; and other functions, including antimicrobial and antitumor effects. Finally, critical biosafety considerations associated with PFHs and perspectives on developing intelligent PFHs are addressed. This review aims to inspire further research on PFHs and accelerate their applications in bone tissue engineering.

Cell-free DNA (cfDNA) holds significant promise for diagnostic and therapeutic advancements in medicine. This review delineates the utility of cfDNA in diagnostics and its therapeutic potential through clearance mechanisms for an array of diseases. Damage-associated molecular patterns (DAMPs) are endogenous molecules released by host cells during stress, or injury. As a trigger for inflammatory responses via damage-associated molecular patterns (DAMPs), cfDNA's removal via nanotechnological approaches can attenuate inflammation and promote tissue repair. While the application of cfDNA clearance is particularly auspicious in cancer, sepsis, and inflammatory conditions, it is confronted with challenges including toxicity, specificity, and the rigors of clinical trial validation. Collectively, this review delineates novel therapeutic targets to inform the development of innovative treatment strategies.

This study investigates a novel light-activated implant system designed for injectable, dose-controlled, sustained drug delivery. The light-activated implant was developed by incorporating light-activated drug-releasing liposomes into a biodegradable polymeric capsule. The drug release kinetics from the implant at 0, 1, and 2 min of light activation were determined in vitro using a tissue mimic with varying depths. A pulsed near-infrared laser at 1064 nm, connected to an optical fiber, was used as the light source. The dexamethasone sodium phosphate (DSP) release was tunable depending on the laser irradiation time, with an approximately 4% reduction in release as tissue depth increased by 2 mm. The implant was injected using a needle into ex vivo porcine vocal folds, and drug release kinetics were quantified by real-time fluorescence imaging. Mathematical models were also developed to understand diffusion mechanisms of the light-activated, controlled drug release profiles from the cylindrical implant. Finally, in vivo evaluations in a healthy rabbit vocal fold model confirmed comparable drug release through light activation. Histological assessments demonstrated the safety of the drug delivery system and the structural integrity of the implant within biological tissues after 6 weeks of implantation. These results support the potential clinical application of the drug delivery system, offering a promising solution for conditions requiring precise, controlled therapeutic delivery. Future work will focus on scaling the technology for clinical trials, including construct and tissue reactions in human tissue, to enhance treatment efficacy for various medical conditions.

This study explores the synergistic therapeutic potential of Prussian Blue Erbium-Doped Hydroxyapatite (PB-Er-HAp) bioceramics in the context of photothermal therapy (PTT) and photodynamic therapy (PDT) for cancer treatment, highlighting their role in multimodal therapeutic approaches and imaging. PB-Er-HAp nanoparticles (NPs) were synthesized using a facile coprecipitation method to incorporate erbium (Er) into nanostructured hydroxyapatite (HAp) at various concentrations. Prussian Blue (PB) was functionalized onto the surfaces of these NPs, resulting in a final particle size of less than 50 nm. The therapeutic efficacy of the synthesized 1.0 mol % PB-Er-HAp NPs was evaluated in vitro, using MDA-MB-231 breast cancer cells. In vitro studies demonstrated that the PB-Er-HAp NPs exhibited significant PTT and PDT effects under 808 nm laser irradiation, effectively inducing cancer cell death through heat generation and reactive oxygen species production, respectively. In vitro experiments validated the ability of NPs to inhibit tumor growth in the MDA-MB-231 breast cancer cell line. This study emphasizes the potential of PB-Er-HAp NPs as a versatile platform for synergistic cancer therapy, combining PTT and PDT effects, while offering capabilities for biomedical imaging. Future research aims to further optimize these NPs and explore their clinical application, aiming toward enhanced therapeutic outcomes in cancer treatment.

As breast cancer progresses to stage IV, it metastasizes to secondary organs, with a strong propensity for bone colonization. Bone metastasis results in dramatically decreased survival rates and currently lacks a definitive cure. To improve survival rates significantly, there is a need for complex and precise in vitro models that can accurately replicate advanced-stage breast cancer for drug screening purposes. Previously, we established a 3D nanoclay in vitro model of bone metastatic breast cancer using human mesenchymal stem cells in combination with either commercial breast cancer cells (MCF-7 and MDA-MB-231) or patient-derived cells (NT013 and NT023) from the primary breast cancer site. In the present study, the efficacy of the in vitro model to distinguish and differentiate between the severity of metastasis in a total of eight patient-derived cell lines representing various subtypes was evaluated. We also tested the effects of the phytochemically enriched plant extract, Rhodiola crenulata, on eight patient-derived cell lines (NT015, NT017, NT021, NT042, NT045, and NT046, in addition to NT013 and NT023) in bone metastatic (BM) culture. Our results confirmed that the cell lines maintained their subtype-specific characteristics after isolation and formed tumors within the bone microenvironment. Additionally, we assessed the impact of these cell lines on Wnt signaling pathways, identifying which lines upregulate or downregulate Wnt signaling through ET-1 and DKK-1 cytokine levels. Within each subtype, we observed differences in the severity of metastasis between patients. R. crenulata induced cytotoxicity in most patient-derived BM cultures, though NT042 BM cultures showed minimal response. In summary, our study has established a patient-derived bone-metastatic breast cancer model that is well-suited for personalized drug screening aimed at treating late-stage breast cancer. This bone metastatic testbed has the capability to evaluate the severity of metastasis within breast cancer subtypes for individual patients.

Spinal cord injury (SCI) can cause irreversible nerve damage, imposing a significant burden on both patients and society. Methylprednisolone (MP), the recommended clinical drug, possesses antioxidant, anti-inflammatory, and antiapoptotic effects. It improves nerve damage by inhibiting secondary pathological processes. However, high-dose MP administration may result in side effects, including diabetes, femoral head necrosis, and infections. Therefore, there is a need to identify safer alternatives to mitigate the issues associated with MP administration. Rutin, a natural small molecule, exhibits multifaceted therapeutic capabilities and high biosafety, making it a promising alternative to MP treatment. However, its poor solubility and rapid metabolism limit its in vivo bioavailability. In this study, a drug-free polypeptide (PAH) containing hydrazide groups on the side chains is designed, which can be used for mitigating secondary SCI through scavenging toxic aldehydes. Then, we utilize PAH to encapsulate rutin and develop aldehyde-responsive nanomedicine for intravenous administration in SCI rats, providing a novel approach for the clinical replacement of MP.