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1.
ACS Biomater Sci Eng ; 10(7): 4411-4424, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38913499

RESUMO

Diabetic bone defects, exacerbated by hyperglycemia-induced inflammation and oxidative stress, present significant therapeutic challenges. This study introduces a novel injectable scaffold, MgH2@PLGA/F-GM, consisting of foamed gelatin-methacryloyl (GelMA) and magnesium hydride (MgH2) microspheres encapsulated in poly(lactic-co-glycolic acid) (PLGA). This scaffold is uniquely suited for diabetic bone defects, conforming to complex shapes and fostering an environment conducive to tissue regeneration. As it degrades, Mg(OH)2 is released and dissolved by PLGA's acidic byproducts, releasing therapeutic Mg2+ ions. These ions are instrumental in macrophage phenotype modulation, inflammation reduction, and angiogenesis promotion, all vital for diabetic bone healing. Additionally, hydrogen (H2) released during degradation mitigates oxidative stress by diminishing reactive oxygen species (ROS). This multifaceted approach not only reduces ROS and inflammation but also enhances M2 macrophage polarization and cell migration, culminating in improved angiogenesis and bone repair. This scaffold presents an innovative strategy for addressing the complexities of diabetic bone defect treatment.


Assuntos
Gelatina , Hidrogéis , Hidrogênio , Magnésio , Gelatina/química , Magnésio/química , Hidrogênio/química , Hidrogênio/farmacologia , Hidrogênio/uso terapêutico , Hidrogênio/administração & dosagem , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Regeneração Óssea/efeitos dos fármacos , Metacrilatos/química , Preparações de Ação Retardada/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Alicerces Teciduais/química , Espécies Reativas de Oxigênio/metabolismo , Células RAW 264.7 , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Estresse Oxidativo/efeitos dos fármacos
2.
ACS Biomater Sci Eng ; 9(8): 4994-5005, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37493452

RESUMO

Human decalcified bone matrix (HDBM) is a framework with a porous structure and good biocompatibility. Nevertheless, its oversized pores lead to massive cell loss when seeding chondrocytes directly over it. Gelatin (GT) is a type of protein obtained by partial hydrolysis of collagen. The GT scaffold can be prepared from the GT solution through freeze-drying. More importantly, the pore size of the GT scaffold can be controlled by optimizing the concentration of the GT solution. Similarly, when different concentrations of gelatin are combined with HDBM and then freeze-dried, the pore size of the HDBM can be modified to different degrees. In this study, the HDBM framework was modified with 0.3, 0.6, and 0.9%GT, resulting in an improved pore size and adhesion rate. Results showed that the HDBM framework with 0.6%GT (HDBM-0.6%GT) had an average pore size of 200 µm, which was more suitable for chondrocyte seeding. Additionally, our study validated that porcine decalcified bone matrix (PDBM) had a proper pore structure. Chondrocytes were in vitro seeded on the three frameworks for 4 weeks and then implanted in nude mice and autologous goats, respectively. The in vivo cartilage regeneration results showed that HDBM-0.6%GT and PDBM frameworks compensated for the oversized pores of the HDBM framework. Moreover, they showed successfully regenerated more mature cartilage tissue with a certain shape in animals.


Assuntos
Matriz Óssea , Alicerces Teciduais , Camundongos , Suínos , Humanos , Animais , Alicerces Teciduais/química , Gelatina/farmacologia , Gelatina/química , Camundongos Nus , Cartilagem
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