RESUMO
Bone regeneration is a complex process that requires the coordination of various biological events. Developing a tissue regeneration membrane that can regulate this cascade of events is challenging. In this study, we aimed to fabricate a membrane that can enrich the damaged area with mesenchymal stem cells, improve angiogenesis, and continuously induce osteogenesis. Our approach involved creating a hierarchical polycaprolactone/gelatin (PCL/GEL) co-electrospinning membrane that incorporated substance P (SP)-loaded GEL fibers and simvastatin (SIM)-loaded PCL fibers. The membrane could initiate a burst release of SP and a slow/sustained release of SIM for over a month. In vitro experiments, including those related to angiogenesis and osteogenesis (e.g., migration, endothelial network formation, alkaline phosphatase activity, mineralization, and gene expression), clearly demonstrated the membrane's superior ability to improve cell homing, revascularization, and osteogenic differentiation. Furthermore, a series of in vivo studies, including immunofluorescence of CD29+/CD90+ double-positive cells and immunohistochemical staining for CD34 and vWF, confirmed the co-electrospinning membrane's ability to enhance MSC migration and revascularization response after five days of implantation. After one month, the Micro-CT and histological (Masson and H&E) results showed accelerated bone regeneration. Our findings suggest that a co-electrospinning membrane with time-tunable drug delivery could advance the development of tissue engineering therapeutic strategies and potentially improve patient outcomes.
RESUMO
The accelerating bone healing process is still a major challenge in clinical orthopedics, especially in critical-sized bone defects. Recently, Nanofiber membranes are showing increasing attention in the biomedical field due to their good biocompatibility, mechanical stability, and the ability to work as a drug carrier to achieve localized and sustained drug delivery. Herein, a multifunction nanofiber membrane loaded with vitamin D (Vit D) and curcumin (Cur) was successfully fabricated using electrospinning technology. In addition, we innovatively modified Vit D with PEG to improve the hydrophilicity of PCL nanofibers. The vitro results of CCK-8, alkaline phosphatase (ALP) and mineralization demonstrated that the PCL/Vit D-Cur membrane had great potential for enhancing the proliferation/differentiation of osteoblasts. Moreover, the synergistic effect of Vit D-Cur loaded PCL nanofiber membrane showed a superior ability to improve the anti-inflammatory activity through M2 polarization. Furthermore, in vivo results confirmed that the defect treated with PCL/Vit D-Cur nanofiber membrane was filled with the newly formed bone after 1 month. These results indicate that the Vit D/Cur loaded membrane can be applied for potential bone regeneration therapy.
RESUMO
Hydrogen sulfide (H2S) has been as an essential gasotransmitter and a potential therapeutic approach for several biomedical treatments such as cardiovascular disorders, hypertension, and other diseases. The endogenous and exogenous H2S also plays a crucial role in the bone anabolic process and a protective mechanism in cell signalling. In this study, we have utilized two types of polymers, polycaprolactone (PCL) and gelatin (Gel), for the fabrication of JK-2 (H2S donor) loaded nanofibrous scaffold via electrospinning process for bone healing and bone tissue engineering. Comparing the PCL/Gel and PCL/Gel-JK-2 scaffolds, the latter demonstrated enhanced cell adhesion and proliferation capabilities. Furthermore, both experimental scaffolds have been subjected to an in vivo experiment for 4 and 8 weeks in a bone-defect model of a rabbit to determine their biological responses under physiological conditions. There was an obvious increase in bone regeneration in the PCL/Gel-JK-2 group compared to the control and PCL/Gel groups. These results indicate the use of PCL/Gel scaffolds loaded with JK-2 should be considered for possible bone regeneration.
