RESUMO
Epidural adhesion or epidural fibrosis is the major reason for postoperative pain, which remains a clinically challenging problem. Current physical barriers fail to provide a satisfactory therapeutic outcome mainly due to their lack of adhesion, inability to prevent fluid leakage, and exhibiting limited antioxidant properties. Herein, we fabricated a cysteine-modified bioadhesive (SECAgel) with improved sealing and antioxidant properties for epidural adhesion prevention, inspired by the organism's antioxidant systems. The resulting SECAgel showed good injectability and in situ adhesion ability, effectively covering every corner of the irregular wound. Besides, it possessed efficient sealing properties (395.2 mmHg), effectively stopping blood leakage in the rabbit carotid artery transection model. The antioxidant experiments demonstrated that the SECAgel effectively scavenged various radicals and saved the cells from oxidative stress. Two animal models were used to show that the SECAgel effectively inhibited adhesion in both situations with and without cerebrospinal fluid leakage. The RNA sequencing analysis showed that SECAgel treatment effectively inhibited the expression of key genes related to adhesion development, inflammatory response, and oxidative stress. The SECAgel, together with good biocompatibility, can be a good candidate for preventing epidural adhesion in the clinic.
Assuntos
Antioxidantes , Animais , Coelhos , Antioxidantes/farmacologia , Antioxidantes/química , Aderências Teciduais/prevenção & controle , Espaço Epidural/patologia , Espaço Epidural/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Cisteína/química , Cisteína/farmacologia , Humanos , Camundongos , Adesivos/química , Adesivos/farmacologia , MasculinoRESUMO
Diabetic wounds remain a global challenge due to disordered wound healing led by inflammation, infection, oxidative stress, and delayed proliferation. Therefore, an ideal wound dressing for diabetic wounds not only needs tissue adhesiveness, injectability, and self-healing properties but also needs a full regulation of the microenvironment. In this work, adhesive wound dressings (HA-DA/PRP) with injectability were fabricated by combining platelet rich plasma (PRP) and dopamine-modified-hyaluronic acid (HA-DA). The engineered wound dressings exhibited tissue adhesiveness, rapid self-healing, and shape adaptability, thereby enhancing stability and adaptability to irregular wounds. The in vitro experiments demonstrated that HA-DA/PRP adhesives significantly promoted fibroblast proliferation and migration, attributed to the loaded PRP. The adhesives showed antibacterial properties against both gram-positive and negative bacteria. Moreover, in vitro experiments confirmed that HA-DA/PRP adhesives effectively mitigated oxidative stress and inflammation. Finally, HA-DA/PRP accelerated the healing of diabetic wounds by inhibiting bacterial growth, promoting granulation tissue regeneration, accelerating neovascularization, facilitating collagen deposition, and modulating inflammation through inducing M1 to M2 polarization, in an in vivo model of infected diabetic wounds. Overall, HA-DA/PRP adhesives with the ability to comprehensively regulate the microenvironment in diabetic wounds may provide a novel approach to expedite the diabetic wounds healing in clinic.
Assuntos
Antibacterianos , Diabetes Mellitus Experimental , Ácido Hialurônico , Hidrogéis , Plasma Rico em Plaquetas , Cicatrização , Ácido Hialurônico/química , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Plasma Rico em Plaquetas/química , Antibacterianos/farmacologia , Antibacterianos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Ratos , Bandagens , Masculino , Proliferação de Células/efeitos dos fármacos , Humanos , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacos , Dopamina/química , Fibroblastos/efeitos dos fármacos , Adesivos/química , Adesivos/farmacologiaRESUMO
Cannabidiol (CBD) is the most relevant nonpsychostimulant phytocompound found in Cannabis sativa. CBD has been extensively studied and has been proposed as a therapeutic candidate for neuroinflammation-related conditions. However, being a highly lipophilic drug, it has several drawbacks for pharmaceutical use, including low solubility and high permeability. Synthetic polymers can be used as drug delivery systems to improve CBD's stability, half-life, and biodistribution. Here, we propose using a synthetic polymer as a nanoparticulate vehicle for CBD (NPCBD) to overcome the pharmacological drawbacks of free drugs. We tested the NPCBD-engineered system in the context of ischemic events in a relevant oxygen and glucose deprivation (OGD) model in primary cortical cells (PCC). Moreover, we have characterized the inflammatory response of relevant cell types, such as THP-1 (human monocytes), HMC3 (human microglia), and PCC, to NPCBD and observed a shift in the inflammatory state of the treated cells after the ischemic event. In addition, NPCBD exhibited a promising ability to restore mitochondrial function after OGD insult in both HMC3 and PCC cells at low doses of 1 and 0.2 µM CBD. Taken together, these results suggest the potential for preclinical use.