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1.
Nanoscale ; 16(17): 8236-8255, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38584466

RESUMO

Osteoporosis, characterized by a reduction in bone mineral density, represents a prevalent skeletal disorder with substantial global health implications. Conventional therapeutic strategies, exemplified by bisphosphonates and hormone replacement regimens, though effective, encounter inherent limitations and challenges. Recent years have witnessed the surge of cell-membrane-coated nanoparticles (CMNPs) as a promising intervention for osteoporosis, leveraging their distinct attributes including refined biocompatibility, heightened pharmaceutical payload capacity, as well as targeted drug release kinetics. However, a comprehensive review consolidating the application of CMNPs-based therapy for osteoporosis remains absent within the existing literature. In this review, we provide a concise overview of the distinctive pathogenesis associated with osteoporosis, alongside an in-depth exploration of the physicochemical attributes intrinsic to CMNPs derived from varied cellular sources. Subsequently, we explore the potential utility of CMNPs, elucidating emerging trends in their deployment for osteoporosis treatment through multifaceted therapeutic approaches. By linking the notable attributes of CMNPs with their roles in mitigating osteoporosis, this review serves as a catalyst for further advances in the design of advanced CMNPs tailored for osteoporosis management. Ultimately, such progress is promising for enhancing outcomes in anti-bone loss interventions, paving the way for clinical translation in the near future.


Assuntos
Membrana Celular , Nanopartículas , Osteoporose , Humanos , Osteoporose/tratamento farmacológico , Nanopartículas/química , Nanopartículas/uso terapêutico , Membrana Celular/metabolismo , Membrana Celular/química , Sistemas de Liberação de Medicamentos , Animais
2.
Bioact Mater ; 34: 366-380, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38269308

RESUMO

Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, the discovery of neddylation, a new type of post-translational modification, has been found to regulate various crucial biological processes including cell metabolism and the cell cycle. Nevertheless, its capacity to control the healing of wounds in diabetic patients remains unknown. This study shows that MLN49224, a compound that inhibits neddylation at low concentrations, enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors. Moreover, it concurrently stimulates the growth, movement, and formation of blood vessel endothelial cells, leading to expedited healing of wounds in individuals with diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area. The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes, along with the polarization of macrophages towards the anti-inflammatory M2 phenotype. By loading M-NPs/MLN4924 into a hydrogel, the final formulation is able to meaningfully repair a diabetic wound, suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.

3.
Biomaterials ; 305: 122461, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171119

RESUMO

Fracture healing is a complex biological process that involves the orchestrated interplay of various cells and molecular signaling pathways. Among the key players, macrophages have emerged as critical regulators of fracture repair, influencing inflammation, tissue remodeling, and angiogenesis. Recent advances in hydrogel-based therapeutics have provided exciting opportunities to leverage the modulatory effects of macrophages for improving fracture healing outcomes. In the present study, we review the importance of macrophages in fracture repair and their potential therapeutic role in hydrogel-based interventions. We discuss the molecular mechanisms underlying macrophage-mediated effects on fracture healing, and how hydrogels can be utilized as a platform for macrophage modulation. Furthermore, we highlight the translation of hydrogel-based therapies from bench to bedside, including preclinical and clinical studies, and the challenges and opportunities in harnessing the therapeutic potential of macrophages in fracture repair. Overall, understanding the importance of macrophages in fracture healing and the potential of hydrogel-based therapeutics to modulate macrophage responses can pave the way for developing innovative approaches to improve fracture healing outcomes.


Assuntos
Consolidação da Fratura , Fraturas Ósseas , Humanos , Hidrogéis/farmacologia , Macrófagos/metabolismo , Inflamação/metabolismo
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