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1.
Biomater Sci ; 12(4): 821-836, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38168805

RESUMO

Islet transplantation holds significant promise as a curative approach for type 1 diabetes (T1D). However, the transition of islet transplantation from the experimental phase to widespread clinical implementation has not occurred yet. One major hurdle in this field is the challenge of insufficient vascularization and subsequent early loss of transplanted islets, especially in non-intraportal transplantation sites. The establishment of a fully functional vascular system following transplantation is crucial for the survival and secretion function of islet grafts. This vascular network not only ensures the delivery of oxygen and nutrients, but also plays a critical role in insulin release and the timely removal of metabolic waste from the grafts. This review summarizes recent advances in effective strategies to improve graft revascularization and enhance islet survival. These advancements include the local release and regulation of angiogenic factors (e.g., vascular endothelial growth factor, VEGF), co-transplantation of vascular fragments, and pre-vascularization of the graft site. These innovative approaches pave the way for the development of effective islet transplantation therapies for individuals with T1D.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Humanos , Ilhotas Pancreáticas/metabolismo , Diabetes Mellitus Tipo 1/cirurgia , Materiais Biocompatíveis , Fator A de Crescimento do Endotélio Vascular/metabolismo , Transplante das Ilhotas Pancreáticas/fisiologia , Neovascularização Fisiológica
2.
Int J Biol Macromol ; 261(Pt 1): 129704, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272431

RESUMO

Chronic diabetic wounds pose a serious threat to human health and safety because of their refractory nature and high recurrence rates. The formation of refractory wounds is associated with wound microenvironmental factors such as increased expression of proinflammatory factors and oxidative stress. Bilirubin is a potent endogenous antioxidant, and morin is a naturally active substance that possesses anti-inflammatory and antioxidant effects. Both hold the potential for diabetic wound treatment by intervening in pathological processes. In this study, we developed bilirubin/morin-based carrier-free nanoparticles (BMn) to treat chronic diabetic wounds. In vitro studies showed that BMn could effectively scavenge overproduced reactive oxygen species and suppress elevated inflammation, thereby exerting a protective effect. BMn was then loaded into a collagen/polyvinyl alcohol gel (BMn@G) for an in vivo study to maintain a moist environment for the skin and convenient biomedical applications. BMn@G exhibits excellent mechanical properties, water retention capabilities, and in vivo safety. In type I diabetic mice, BMn@G elevated the expression of the anti-inflammatory factor IL-10 and concurrently diminished the expression of the proinflammatory factor TNF-α in the tissues surrounding the wounds. Furthermore, BMn@G efficiently mediated macrophage polarization from the M1-type to the M2-type, thereby fostering anti-inflammatory effects. Additionally, BMn@G facilitated the conversion of type III collagen fiber bundles to type I collagen fiber bundles, resulting in a more mature collagen fiber structure. This study provides a promising therapeutic alternative for diabetic wound healing.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus , Flavonas , Nanopartículas , Camundongos , Humanos , Animais , Álcool de Polivinil/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Bilirrubina/metabolismo , Cicatrização , Colágeno/química , Inflamação/patologia , Anti-Inflamatórios/uso terapêutico , Flavonoides/uso terapêutico , Estresse Oxidativo , Hidrogéis/uso terapêutico , Diabetes Mellitus/tratamento farmacológico
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