Sodium alginate hydrogels co-encapsulated with cell free fat extract-loaded core-shell nanofibers and menstrual blood stem cells derived exosomes for acceleration of articular cartilage regeneration.

This study presents a novel scaffold system comprising sodium alginate hydrogels (SAh) co-encapsulated with cell-free fat extract (CEFFE)-loaded core-shell nanofibers (NFs) and menstrual blood stem cell-derived exosomes (EXOs). The scaffold integrates the regenerative potential of EXOs and CFFFE, offering a multifaceted strategy for promoting articular cartilage repair. Coaxially electrospun core-shell NFs exhibited successful encapsulation of CEFFE and seamless integration into the SAh matrix. Structural modifications induced by the incorporation of CEFFE-NFs enhanced hydrogel porosity, mechanical strength, and degradation kinetics, facilitating cell adhesion, proliferation, and tissue ingrowth. The release kinetics of growth factors from the composite scaffold demonstrated sustained and controlled release profiles, essential for optimal tissue regeneration. In vitro studies revealed high cell viability, enhanced chondrocyte proliferation, and migration in the presence of EXOs/CEFFE-NFs@SAh composite scaffolds. Additionally, in vivo experiments demonstrated significant cartilage regeneration, with the composite scaffold outperforming controls in promoting hyaline cartilage formation and defect bridging. Overall, this study underscores the potential of EXOs and CEFFE-NFs integrated into SAh matrices for enhancing chondrocyte viability, proliferation, migration, and ultimately, articular cartilage regeneration. Future research directions may focus on elucidating underlying mechanisms and conducting long-term in vivo studies to validate clinical applicability and scalability.

Mesenchymal stem cell secretome: A promising therapeutic strategy for erectile dysfunction?

Objective: The secretome, comprising bioactive chemicals released by mesenchymal stem cells (MSCs), holds therapeutic promise in regenerative medicine. This review aimed to explore the therapeutic potential of the MSC secretome in regenerative urology, particularly for treating erectile dysfunction (ED), and to provide an overview of preclinical and clinical research on MSCs in ED treatment and subsequently to highlight the rationales, mechanisms, preclinical investigations, and therapeutic potential of the MSC secretome in this context. Methods: The review incorporated an analysis of preclinical and clinical research involving MSCs in the treatment of ED. Subsequently, it delved into the existing knowledge regarding the MSC secretome, exploring its therapeutic potential. The methods included a comprehensive examination of relevant literature to discern the processes underlying the therapeutic efficacy of the MSC secretome. Results: Preclinical research indicated the effectiveness of the MSC secretome in treating various models of ED. However, the precise mechanisms of its therapeutic efficacy remain unknown. The review provided insights into the anti-inflammatory, pro-angiogenic, and trophic properties of the MSC secretome. It also discussed potential advantages, such as avoiding issues related to cellular therapy, including immunogenicity, neoplastic transformation, and cost. Conclusion: This review underscores the significant therapeutic potential of the MSC secretome in regenerative urology, particularly for ED treatment. While preclinical studies demonstrate promising outcomes, further research is essential to elucidate the specific mechanisms underlying the therapeutic efficacy before clinical application. The review concludes by discussing future perspectives and highlighting the challenges associated with the clinical translation of the MSC secretome in regenerative urology.

Bioactive Wound Healing 3D Structure Based on Chitosan Hydrogel Loaded with Naringin/Cyclodextrin Inclusion Nanocomplex.

The current assay aimed to fabricate and analyze a potent wound healing structure based on a naringin (Nar)/ß-cyclodextrin (ß-CD)-loaded chitosan hydrogel. Using the simulation studies, we assessed the interactions among the Nar, ß-CD, and the formation of the inclusion complex. Then, the formation of the hydrogel nanocomplex was simulated and evaluated using the in silico methods. The results showed that after optimization of the structures by DMol3 based on DFT-D, the total energies of Nar, GP, CD, and ß-CD were calculated at -2100.159, -912.192, -3778.370, and -4273.078 Ha, respectively. The encapsulation energy of Nar on ß-CD in the solvent phase was calculated at -93.626 kcal/mol, and the Nar structure was located inside ß-CD in solution. The negative interaction energy value for the encapsulation of Nar on ß-CD suggests the exothermic adsorption process and a stable structure between Nar and ß-CD. Monte Carlo method was applied to obtain adsorption of CS/GP on Nar/ß-CD. Its value of the obtained interaction energy was calculated at -1.423 × 103 kcal/mol. The characterization confirmed the formation of a Nar/ß-CD inclusion complex. The Zeta potential of the pristine ß-CD changed from -4.60 ± 1.1 to -17.60 ± 2.34 mV after interaction with Nar, and the heightened surface negativity can be attributed to the existence of electron-rich naringin molecules, as well as the orientation of the hydroxyl (OH) group of the ß-CD toward the surface in an aqueous solution. The porosity of the fabricated hydrogels was in the range of 70-90% and during 14 days around 47.0 ± 3.1% of the pure hydrogel and around 56.4 ± 5.1 of hydrogel nanocomposite was degraded. The MTT assay showed that the hydrogels were biocompatible, and the wound contraction measurement (in an animal model) showed that the closure of the induced wound in the hydrogel nanocomposite treatment was faster than that of the control group (wound without treatment). The results of this study indicate that the developed bioactive wound healing 3D structure, which is composed of a chitosan hydrogel containing a Nar/ß-CD inclusion nanocomplex, has potential as an effective material for wound dressing applications.

Enhancing osteogenic differentiation of dental pulp stem cells through rosuvastatin loaded niosomes optimized by Box-Behnken design and modified by hyaluronan: a novel strategy for improved efficiency.

Bone tissue engineering necessitates a stem cell source capable of osteoblast differentiation and mineralized matrix production. Dental pulp stem cells (DPSCs), a subtype of mesenchymal stem cells from human teeth, present such potential but face challenges in osteogenic differentiation. This research introduces an innovative approach to bolster DPSCs' osteogenic potential using niosomal and hyaluronan modified niosomal systems enriched with rosuvastatin. While rosuvastatin fosters bone formation by regulating bone morphogenetic proteins and osteoblasts, its solubility, permeability, and bioavailability constraints hinder its bone regeneration application. Using a Box-Behnken design, optimal formulation parameters were ascertained. Both niosomes were analyzed for size, polydispersity, zeta potential, and other parameters. They displayed average sizes under 275 nm and entrapment efficiencies exceeding 62%. Notably, niosomes boosted DPSCs' cell viability and osteogenic marker expression, suggesting enhanced differentiation and bone formation. Conclusively, the study underscores the potential of both niosomal systems in ameliorating DPSCs' osteogenic differentiation, offering a promising avenue for bone tissue engineering and regeneration.

Implantable smart hyperthermia nanofibers for cancer therapy: Challenges and opportunities.

Nanofibers (NFs) with practical drug-loading capacities, high stability, and controllable release have caught the attention of investigators due to their potential applications in on-demand drug delivery devices. Developing novel and efficient multidisciplinary management of locoregional cancer treatment through the design of smart NF-based systems integrated with combined chemotherapy and hyperthermia could provide stronger therapeutic advantages. On the other hand, implanting directly at the tumor area is a remarkable benefit of hyperthermia NF-based drug delivery approaches. Hence, implantable smart hyperthermia NFs might be very hopeful for tumor treatment in the future and provide new avenues for developing highly efficient localized drug delivery systems. Indeed, features of the smart NFs lead to the construction of a reversibly flexible nanostructure that enables hyperthermia and facile switchable release of antitumor agents to eradicate cancer cells. Accordingly, this study covers recent updates on applications of implantable smart hyperthermia NFs regarding their current scope and future outlook. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

Epidural Administration of Curcumin-Loaded Polycaprolactone/Gelatin Electrospun Nanofibers for Extended Analgesia After Laminectomy in Rats.

Several clinical studies have reported the analgesic effect of curcumin (Curc) in various situations such as rheumatoid arthritis, osteoarthritis, and postsurgical pain. Therefore, in this work, Curc-loaded electrospun nanofibers (NFs) are designed to evaluate their sustained release on analgesic effect duration in rats after epidural placement via repeated formalin and tail-flick tests. The Curc-loaded polycaprolactone/gelatin NFs (Curc-PCL/GEL NFs) are prepared through an electrospinning technique and introduced to the rat's epidural space after laminectomy. The physicochemical and morphology features of the prepared Curc-PCL/GEL NFs were characterized via FE-SEM, FTIR, and degradation assay. The in vitro and in vivo concentrations of Curc were measured to evaluate the analgesic efficacy of the drug-loaded NFs. Rat nociceptive responses are investigated through repeated formalin and tail-flick tests for 5 weeks after the placement of NFs. Curc had a sustained release from the NFs for 5 weeks, and its local pharmaceutical concentrations were much greater than plasma concentrations. Rat's pain scores in both early and late phases of the formalin test were remarkably decreased in the experimental period. Rat's tail-flick latency was remarkably enhanced and remained constant for up to 4 weeks. Our findings show that the Curc-PCL/GEL NFs can supply controlled release of Curc to induce extended analgesia after laminectomy.

Curcumin-Loaded Mesenchymal Stem Cell-Derived Exosomes Efficiently Attenuate Proliferation and Inflammatory Response in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

This study aimed to evaluate the potential of mesenchymal stem cell-derived exosomes loaded with curcumin (Curc-Exos) as an effective therapeutic strategy for rheumatoid arthritis through modulation of proliferation and inflammatory response in HIG-82 synovial cells. For this purpose, Exos were isolated and characterized with BCA protein assay, DLS, FE-SEM, and TEM. The Curc was embedded by mixing it with Exos in a 1:4 ratio. It was found that the Curc stability has improved after loading on Exos compared to the free Curc. Besides, the in vitro studies using LPS-stimulated HIG-82 synovial cells indicated the efficiency of Curc-Exos in enhancing cytotoxicity and apoptosis compared to the free Curc treatment. It was also revealed that Curc-Exos significantly could reduce the expression levels of anti-apoptotic proteins IAP1 and IAP2 and inflammatory mediators including IL-6, TNF-α, MMP1, and PGE2. This preliminary study confirmed the suitability of Curc-Exos in counteracting the proliferation and inflammatory response of rheumatoid arthritis synovial fibroblasts in vitro.

Implantable magnetic nanofibers with ON-OFF switchable release of curcumin for possible local hyperthermic chemotherapy of melanoma.

Implantable thermo-responsive drug-loaded magnetic nanofibers (NFs) have attracted great interest for localized thermo-chemotherapy of cancer tissue/cells. From this perspective, smart polymeric electrospun NFs co-loaded with magnetic nanoparticles (MNPs) and a natural polyphenol anticancer agent, curcumin (CUR), were developed to enhance the local hyperthermic chemotherapy against melanoma, the most serious type of skin cancer. CUR/MNPs-loaded thermo-sensitive electrospun NFs exhibited alternating magnetic field (AMF)-responsive heat generation and "ON-OFF" switchable heating capability. Besides, corresponding to the reversible alterations in the swelling ratio, the "ON-OFF" switchable discharge of CUR from the magnetic NFs was detected in response to the "ON-OFF" switching of AMF application. Due to the combinatorial effect of hyperthermia and release of CUR after applying an AMF ("ON" state) for 600 s on the second and third days of incubation time, the viability of the B16F10 melanoma cancer cells exposed to the CUR/MNPs-NFs was reduced by 40% and 17%, respectively. Taken together, the macroscopic and nanoscale features of the smart NFs led to the creation of a reversibly adjustable structure that enabled hyperthermia and facile switchable release of CUR for eradication of melanoma cancer cells.

Prolonged proliferation and delayed senescence of the adipose-derived stem cells grown on the electrospun composite nanofiber co-encapsulated with TiO2 nanoparticles and metformin-loaded mesoporous silica nanoparticles.

This study was aimed to investigate the effects of the Poly-ε-Caprolactone/Gelatin nanofibers (PCL/GEL NFs) co-encapsulated with TiO2 nanoparticles (nTiO2) and metformin-loaded mesoporous silica nanoparticles (MET@MSNs) on prolonging the in vitro expansion of human adipose-derived stem cells (hADSCs) without inducing cellular senescence and aging. FTIR, BET, FE-SEM, and TEM were applied to characterize the fabricated MET@MSNs and electrospun composite NFs. The presence of inorganic particles, nTiO2 and MSNs, in the scaffolds improved their mechanical properties and led to a more sustained release of MET with almost the lack of the initial burst release from nTiO2/MET@MSNs-loaded NFs. The enhanced adhesion, metabolic activity, and proliferation rate of the hADSCs grown on nTiO2/MET@MSNs-loaded NFs were demonstrated via FE-SEM images, MTT test and PicoGreen assay, respectively, over 28 days of culture. Furthermore, the irregular nanofibrillar structures and the impact of sustained release of MET led to a significant upregulation in the mRNA levels of autophagy (Atg-5, Atg-7, Atg-12, and Beclin-1) and stemness (Nanog3, Sox-2, and Oct-4) markers as well as a considerable down-regulation of p16INK4A senescence marker. Further, the upregulation of hTERT, enhanced activity of telomerase, and increased telomere length were more pronounced in the hADSCs cultured on nTiO2/MET@MSNs-loaded NFs as compared to other types of NFs. Overall, our findings demonstrated the potential of the fabricated nanocomposite platform for counteracting cellular senescence and achieving sufficient quantities of fresh hADSCs with preserved stemness for various stem cell-based regenerative medicine purposes.