ACS Biomaterials Science & Engineering最新文献

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 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.

Hydrogel wound dressings have emerged as a promising solution for wound healing due to their excellent mechanical and biochemical properties. Over recent years, there has been significant progress in expanding the variety of raw materials used for hydrogel formulation along with the development of advanced modification techniques and design approaches that enhance their performance. However, a comprehensive review encompassing diverse polymer modification strategies and design innovations for hydrogel dressings is still lacking in the literature. This review summarizes the use of natural polymers (e.g., chitosan, gelatin, sodium alginate, hyaluronic acid, and dextran) and synthetic polymers (e.g., poly(vinyl alcohol), polyethylene glycol, Pluronic F-127, poly(N-isopropylacrylamide), polyacrylamide, and polypeptides) in hydrogel wound dressings. We further explore the advantages and limitations of these polymers and discuss various modification strategies, including cationic modification, oxidative modification, double-bond modification, catechol modification, etc. The review also addresses design principles and synthesis methods, aligning polymer modifications with specific requirements in wound healing. Finally, we discuss future challenges and opportunities in the development of advanced hydrogel-based wound dressings.

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.

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.

Drug repurposing is an attractive route for finding new therapeutics for brain cancers such as glioblastoma. Local administration of drugs to brain tumors or the postsurgical resection cavity holds promise to deliver a high dose to the target site with minimal off-target effects. Drug delivery systems aim to sustain the release of the drug at the target site but typically exhibit drawbacks such as a poor safety profile, uncontrolled/rapid drug release, or poor control over synthesis parameters/material dimensions. Herein, we analyzed the antidepressant vortioxetine and showed in vitro that it causes a greater loss of viability in glioblastoma cells than it does to normal primary human astrocytes. We developed a new droplet microfluidic-based emulsion method to reproducibly produce vortioxetine-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres with tight size control (36.80 ± 1.96 μm). The drug loading efficiency was around 90% when 9.1% (w/w) drug was loaded into the microspheres, and drug release could be sustained for three to 4 weeks. The vortioxetine microspheres showed robust antiglioblastoma efficacy in both 2D monolayer and 3D spheroid patient-derived glioblastoma cells, highlighting the potential of combining an antidepressant with sustained local delivery as a new therapeutic strategy.

Hydrogel wound dressings have emerged as a promising solution for wound healing due to their excellent mechanical and biochemical properties. Over recent years, there has been significant progress in expanding the variety of raw materials used for hydrogel formulation along with the development of advanced modification techniques and design approaches that enhance their performance. However, a comprehensive review encompassing diverse polymer modification strategies and design innovations for hydrogel dressings is still lacking in the literature. This review summarizes the use of natural polymers (e.g., chitosan, gelatin, sodium alginate, hyaluronic acid, and dextran) and synthetic polymers (e.g., poly(vinyl alcohol), polyethylene glycol, Pluronic F-127, poly(N-isopropylacrylamide), polyacrylamide, and polypeptides) in hydrogel wound dressings. We further explore the advantages and limitations of these polymers and discuss various modification strategies, including cationic modification, oxidative modification, double-bond modification, catechol modification, etc. The review also addresses design principles and synthesis methods, aligning polymer modifications with specific requirements in wound healing. Finally, we discuss future challenges and opportunities in the development of advanced hydrogel-based wound dressings.

Drug repurposing is an attractive route for finding new therapeutics for brain cancers such as glioblastoma. Local administration of drugs to brain tumors or the postsurgical resection cavity holds promise to deliver a high dose to the target site with minimal off-target effects. Drug delivery systems aim to sustain the release of the drug at the target site but typically exhibit drawbacks such as a poor safety profile, uncontrolled/rapid drug release, or poor control over synthesis parameters/material dimensions. Herein, we analyzed the antidepressant vortioxetine and showed in vitro that it causes a greater loss of viability in glioblastoma cells than it does to normal primary human astrocytes. We developed a new droplet microfluidic-based emulsion method to reproducibly produce vortioxetine-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres with tight size control (36.80 ± 1.96 μm). The drug loading efficiency was around 90% when 9.1% (w/w) drug was loaded into the microspheres, and drug release could be sustained for three to 4 weeks. The vortioxetine microspheres showed robust antiglioblastoma efficacy in both 2D monolayer and 3D spheroid patient-derived glioblastoma cells, highlighting the potential of combining an antidepressant with sustained local delivery as a new therapeutic strategy.