Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments.

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.

Bulk Modification with Inorganic Particles and Immobilization of Extracellular Vesicles onto PDO Composite for Facial Rejuvenation.

BACKGROUND: The skin, a vital organ protecting against microorganisms and dehydration, undergoes structural decline with aging, leading to visible issues such as wrinkles and sagging. Reduced blood vessels exacerbate vulnerability, hindering optimal cellular function and compromising skin health. Polydioxanone (PDO) biomaterials address aging concerns but produce acidic byproducts, causing inflammation. Inorganic particles and nitric oxide (NO) play crucial roles in inhibiting inflammation and promoting skin regeneration. Stem cell-derived extracellular vesicles (EVs) contribute to intercellular communication, offering the potential to enhance cell functions. The study proposes a method to enhance PDO-based medical devices by incorporating inorganic particles and immobilizing EVs, focusing on facial rejuvenation, anti-inflammatory response, collagen formation, and angiogenesis. METHOD: PDO composites with inorganic particles such as magnesium hydroxide (MH) and zinc oxide (ZO) were prepared and followed by EV immobilization. Comprehensive characterization included biocompatibility, anti-inflammation, collagen formation ability, and angiogenesis ability. RESULTS: Bulk-modified PDO composites demonstrated even dispersion of inorganic particles, pH neutralization, and enhanced biocompatibility. EVs immobilized on the composite surface exhibited spherical morphology. Inflammation-related gene expressions decreased, emphasizing anti-inflammatory effects. Collagen-related gene and protein expressions increased, showcasing collagen formation ability. In addition, angiogenic capabilities were notably improved, indicating potential for skin rejuvenation. CONCLUSION: The study successfully developed and characterized PDO composites with inorganic particles and EVs, demonstrating promising attributes for medical applications. These composites exhibit biocompatibility, anti-inflammatory properties, collagen formation ability, and angiogenic potential, suggesting their utility in skin rejuvenation and tissue engineering. Further research and clinical validation are essential.

PLLA Composites Combined with Delivery System of Bioactive Agents for Anti-Inflammation and Re-Endothelialization.

The development of a biodegradable vascular scaffold (BVS) for the treatment of cardiovascular diseases (CVDs) still requires some improvement. Among them, re-endothelialization and anti-inflammation are clinically important to restore vascular function. In this study, we proposed a coating system to deliver hydrophilic bioactive agents to BVS using nanoemulsion and drop-casting methods. The poly(L-lactide) (PLLA) scaffold containing magnesium hydroxide (MH) was coated on the surface with bioactive molecules such as polydeoxyribonucleotide (PDRN), L-arginine (Arg, R), and mesenchymal stem cell-derived extracellular vesicles (EVs). PDRN upregulates the expression of VEGF as one of the A2A receptor agonists; and Arg, synthesized into nitric oxide by intracellular eNOS, induces endothelialization. In particular, EVs, which are composed of a lipid bilayer and transfer bioactive materials such as protein and nucleic acid, regulate homeostasis in blood vessels. Such a bioactive agent coating system and its PLLA composite suggest a new platform for the treatment of cardiovascular dysfunction.

Reduced restenosis and enhanced re-endothelialization of functional biodegradable vascular scaffolds by everolimus and magnesium hydroxide.

BACKGROUND: Coronary artery disease is a cardiovascular disease with a high mortality and mortality rate in modern society. Vascular stent insertion to restore blood flow is essential to treat this disease. A fully biodegradable vascular scaffold (BVS) is a vascular poly (L-lactic acid) (PLLA) stent that is receiving growing interest as this is biodegradable in the body and does not require secondary removal surgery. However, acidic byproducts composed of PLLA produced during the biodegradation of the BVS can induce an inflammatory response. Magnesium hydroxide, a basic inorganic particle, neutralizes the acidic byproducts of PLLA.  METHODS: In this study, we investigated using a BVS coated with everolimus and surface-modified magnesium hydroxide that suppresses smooth muscle cell proliferation and protects endothelial cells, respectively. The various characteristics of the functional stent were evaluated using in vitro and in vivo analyses.  RESULTS: The BVS was successfully prepared with evenly coated everolimus and surface-modified magnesium hydroxide. A neutral pH value was maintained by magnesium hydroxide during degradation, and everolimus was released for one month. The coated BVS effectively inhibited protein adsorption and platelet adhesion, demonstrating excellent blood compatibility. In vitro analysis showed that BVS protects endothelial cells with magnesium hydroxide and selectively inhibits smooth muscle cell proliferation via everolimus treatment. The functional BVS was inserted into porcine coronary arteries for 28 days, and the results demonstrated that the restenosis and inflammation greatly decreased and re-endothelialization was enhanced as compared to others. CONCLUSIONS: This study provides new insights into the design of drug-incorporated BVS stent for coronary artery disease.

Enhanced Mechanical Properties and Anti-Inflammation of Poly(L-Lactic Acid) by Stereocomplexes of PLLA/PDLA and Surface-Modified Magnesium Hydroxide Nanoparticles.

Poly(L-lactic acid) (PLLA), as a biodegradable polymer, has attracted attention for use as a biomaterial. In order to apply PLLA as a cardiovascular stent, stronger mechanical properties and anti-inflammatory effects against acidic by-products are required. In this study, PLLA/PDLA stereocomplex microparticles (SC) were developed and surface-modified magnesium hydroxide (MH) nanoparticles with oligolactide were combined with these PLLA composites. The SC improved the mechanical properties of the PLLA composites through the formation of stereocomplex structures. The surface-modified MH nanoparticles showed enhanced mechanical properties due to the stereocomplex structures formed by PLLA chains and inhibited inflammatory responses by pH neutralization as a result of MH. Additionally, the MH nanoparticles containing PLLA composites had antibacterial effects and increased the viability of human vascular endothelial cells. This technology is expected to have great potential in the development of PLLA composite materials for the production of various medical devices, such as cardiovascular stents.

Poly(L-Lactic Acid) Composite with Surface-Modified Magnesium Hydroxide Nanoparticles by Biodegradable Oligomer for Augmented Mechanical and Biological Properties.

Poly(L-lactic acid) (PLLA) has attracted a great deal of attention for its use in biomedical materials such as biodegradable vascular scaffolds due to its high biocompatibility. However, its inherent brittleness and inflammatory responses by acidic by-products of PLLA limit its application in biomedical materials. Magnesium hydroxide (MH) has drawn attention as a potential additive since it has a neutralizing effect. Despite the advantages of MH, the MH can be easily agglomerated, resulting in poor dispersion in the polymer matrix. To overcome this problem, oligo-L-lactide-ε-caprolactone (OLCL) as a flexible character was grafted onto the surface of MH nanoparticles due to its acid-neutralizing effect and was added to the PLLA to obtain PLLA/MH composites. The pH neutralization effect of MH was maintained after surface modification. In an in vitro cell experiment, the PLLA/MH composites including OLCL-grafted MH exhibited lower platelet adhesion, cytotoxicity, and inflammatory responses better than those of the control group. Taken together, these results prove that PLLA/MH composites including OLCL-grafted MH show excellent augmented mechanical and biological properties. This technology can be applied to biomedical materials for vascular devices such as biodegradable vascular scaffolds.

Multifunctional Biodegradable Vascular PLLA Scaffold with Improved X-ray Opacity, Anti-Inflammation, and Re-Endothelization.

Poly(L-lactic acid) (PLLA) has been used as a biodegradable vascular scaffold (BVS) material due to high mechanical property, biodegradability, and biocompatibility. However, acidic byproducts from hydrolysis of PLLA reduce the pH after the surrounding implanted area and cause inflammatory responses. As a result, severe inflammation, thrombosis, and in-stent restenosis can occur after implantation by using BVS. Additionally, polymers such as PLLA could not find on X-ray computed tomography (CT) because of low radiopacity. To this end, here, we fabricated PLLA films as the surface of BVS and divided PLLA films into two coating layers. At the first layer, PLLA film was coated by 2,3,5-triiodobenzoic acid (TIBA) and magnesium hydroxide (MH) with poly(D,L-lactic acid) (PDLLA) for radiopaque and neutralization of acidic environment, respectively. The second layer of coated PLLA films is composed of polydopamine (PDA) and then cystamine (Cys) for the generation of nitric oxide (NO) release, which is needed for suppression of smooth muscle cells (SMCs) and proliferation of endothelial cells (ECs). The characterization of the film surface was conducted via various analyses. Through the surface modification of PLLA films, they have multifunctional abilities to overcome problems of BVS effectively such as X-ray penetrability, inflammation, thrombosis, and neointimal hyperplasia. These results suggest that the modification of biodegradable PLLA using TIBA, MH, PDA, and Cys will have important potential in implant applications.

Photocatalytic Properties of Silver Core/Titania Shell Nano-Wires Grown on a Glass Substrate Using a Glycothermal Process Assisted by a Photochemical Reaction.

A silver core/titania shell nano-wire film was successfully prepared on a glass substrate via a glycothermal process that was assisted by a photochemical reaction using tetra-n-butyl titanate as the titanium source and silver nitrate as the silver source in an autoclave with ethylene glycol as a solvent. The morphology, diameter, length, and density of the core/shell nano-wires that were synthesized could be varied by changing the silver/titanium molar ratio of the starting materials. The samples produced were characterized by X-ray diffraction and scanning electron microscopy. The photocatalytic activity of the silver core/titania shell nano-wire film was investigated by measuring the photodegradation rate of rhodamine B in aqueous solution.

Glycothermal Growth of Silver Core/TiO2 Shell Nano-Wires on FTO Substrate.

Silver core/TiO2 shell nano-wires have been successfully prepared on fluorine doped tin oxide coated glass substrate via a glycothermal process assisted by a photochemical process. The morphology, diameter, length, and density of synthesized core/shell nano-wires could be varied by photochemical reaction time. The fabricated samples were characterized with X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray. We suggested a mechanism to explain the growth of the silver core/TiO2 shell nano-wires.