RESUMO
The pace of bone formation slows down with aging, which leads to the development of osteoporosis. In addition to senescent bone marrow mesenchymal stem cells (S-BMSCs), senescent macrophages (S-MΦs) present in the bone marrow produce numerous inflammatory cytokines that contribute to the inflammaged microenvironment and are involved in the development of osteoporosis. Although autophagy activation has shown a significant anti-aging effect, its influence on inflammaging and its role in osteoporosis treatment remain unclear. Traditional Chinese herbal medicine contains bioactive components that exhibit remarkable advantages in bone regeneration. We have demonstrated that icariin (ICA), a bioactive component of traditional Chinese herbal medicine, activates autophagy, exerts a significant anti-inflammaging effect on S-MΦs, and rejuvenates osteogenesis of S-BMSCs, thereby alleviating bone loss in osteoporotic mice. The transcriptomic analysis further reveals that the TNF-α signaling pathway, which is significantly associated with the level of autophagy, regulates this effect. Moreover, the expression of senescence-associated secretory phenotype (SASP) is significantly reduced after ICA treatment. In summary, our findings suggest that bioactive components/materials targeting autophagy can effectively modulate the inflammaging of S-MΦs, offering an innovative treatment strategy for osteoporosis remission and various age-related comorbidities.
Assuntos
Medicamentos de Ervas Chinesas , Osteoporose , Camundongos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Osteogênese/genética , Autofagia , Diferenciação CelularRESUMO
In this study, a photocurable hydrogel based on an ε-poly-l-lysine (EPL) composite was fabricated by a grafting reaction using glycidyl methacrylate and then complexed with tannic acid (TA) to improve the mechanical stability and antibacterial performance of the EPL hydrogels. UV-visible spectrophotometry, nuclear magnetic resonance, and Fourier transform infrared spectroscopy were introduced to characterize the chemical construction. The obtained EPLMA hydrogel was immersed into TA solution to induce the forming of the H-bond between EPL and TA, resulting in double networks in the composite hydrogel (EPLMA-TA). Due to the additional hydrogen-bond interaction between TA and EPLMA, the mechanical properties of hydrogels were improved and supported cell growth and proliferation. In addition, the antibacterial properties and antioxidant activities of the EPLMA-TA hydrogels were greatly enhanced due to the addition of TA. All the findings indicate that the EPLMA-TA hydrogels with multiple properties show great potential for biomedicine applications.
Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Materiais Biocompatíveis/farmacologia , Hidrogéis/farmacologia , Polilisina/farmacologia , Taninos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antioxidantes/síntese química , Antioxidantes/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Compostos de Bifenilo/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Escherichia coli/citologia , Escherichia coli/efeitos dos fármacos , Hidrogéis/síntese química , Hidrogéis/química , Teste de Materiais , Testes de Sensibilidade Microbiana , Estrutura Molecular , Imagem Óptica , Tamanho da Partícula , Picratos/antagonistas & inibidores , Polilisina/química , Staphylococcus aureus/citologia , Staphylococcus aureus/efeitos dos fármacos , Estresse Mecânico , Taninos/químicaRESUMO
Prevention of bacterial infection and promotion of osseointegration are two important issues for titanium (Ti) implants in medical research. In addition, after a biofilm is formed on the surface of implants, the immune system and antibiotic therapy may fail. In this work, bio-functionalized titanium dioxide (TiO2)/molybdenum disulfide (MoS2)/polydopamine (PDA)/arginine-glycine-aspartic acid (RGD) nanorod arrays (NAs) are prepared on Ti implants to not only kill bacteria noninvasively upon co-irradiation of 660 nm visible light (VL) and 808 nm near infrared (NIR) light, but also promote the osteogenic activity simultaneously. Dual light irradiation triggers the TiO2/MoS2 NA to generate hyperthermia and reactive oxygen species (ROS) in 10 min. The synergistic effects of the generated hyperthermia and ROS increase the bacterial membrane permeability and bacteria are killed rapidly and efficiently in vitro and in vivo. The biofilm is also eradicated and RGD on the nanorods improves cell adhesion, proliferation, and osteogenic differentiation. The strategy described here for the design of bio-functionalized coatings on Ti implants has great clinical potential in orthopedics, dentistry, and other medical fields.