Kirbyfinnegan9750

Polycaprolactone (PCL) is widely used in bone tissue engineering due to its biocompatibility and mechanical strength. However, PCL is not biologically active and shows poor hydrophilicity, making it difficult for new bones to bind tightly to its surface. Magnesium (Mg), an important component of natural bone, exhibits good osteo-inductivity and biological activity. Therefore, porous PCL/Mg scaffolds, including pure PCL, PCL/5%Mg, PCL/10%Mg, and PCL/15%Mg, were prepared to elucidate whether the porous structure of scaffolds and the bioactivity of PCL may be enhanced via 3D printing and incorporation of Mg powder. Compared with the control group (pure PCL only), the hydrophilicity of composite PCL/Mg scaffolds was greatly increased, resulting in the scaffolds having decreased water contact angles. Tests for adhesion and proliferation of rat bone marrow mesenchymal stem cells (rBMSCs) indicated that the PCL/10%Mg scaffold showed superior compatibility. Furthermore, as indicated by alkaline phosphatase (ALP) activity and semiquantitative analysis of alizarin red staining, PCL/10%Mg scaffolds exhibited significantly stronger osteogenic activity than the other scaffolds. Animal experiments demonstrated that PCL/10%Mg scaffolds displayed pro-osteogenic effects at an early stage (4 weeks) and produced more new bone mass 8-12 weeks following implantation, compared with the control group. Visceral and blood parameter analyses indicated that PCL/10%Mg scaffolds did not exert any noticeable toxic effects. PCL/10%Mg composite scaffolds were found to promote bone defect repair at an early stage with good cytocompatibility. This finding revealed a new concept in designing bone tissue materials, which showed potential as a clinical treatment for bone defects.Hyaline cartilage regeneration remains clinically challenging. In this study, microbial transglutaminase was used to cross-link gelatin. The articular cartilage extracellular matrix (cECM), mainly comprising collagen type II and glycosaminoglycans (GAGs), which can support chondrogenesis, was enclosed in this enzyme-catalyzed hydrogel. After human adipose-derived stem cells (hASCs) were encapsulated in the hydrogel enriched with the cECM, the results demonstrated that the enzymatic cross-linking reaction is of low cytotoxicity. Moreover, the stem cells showed great proliferation and chondrogenic differentiation potential in the hydrogel. Most importantly, we assessed the therapeutic effects of applying a hydrogel enriched with the cECM and hASCs to repair a full-thickness osteochondral defect. At 8 weeks after surgery, the GCC group (hydrogel encapsulating cells and the cECM) exhibited a smooth articular surface with transparent new hyaline-like tissue macroscopically. According to histological analysis, inflammatory responses were hardly observed, and sound chondrocytes were aligned in the newly formed chondral layer. In addition, the GCC group exhibited significant improvement in the GAG content between weeks 4 and 8. In summary, the implantation of a gelatin hydrogel enriched with the cECM and hASCs could facilitate the hyaline cartilage regeneration significantly in rabbit knee joint models.The ability of mesenchymal stem cells (MSCs) to enhance cutaneous wound healing has been well established. Extensive expansion of cells to reach sufficient cell numbers for regenerating tissues has always limited cell-based therapies. An ingenious solution to address this challenge is to develop a strategy to increase the immunomodulatory effects of MSCs without expanding them. In this study, we employed a simple characteristic of cells. It was observed that an optimized three-dimensional (3D) MSC culture in spheroid forms significantly improved their paracrine effects. An electrospray (ES) encapsulation apparatus was used to encapsulate individual or 3D spheroid MSCs into microscale alginate beads (microbeads). Furthermore, alginate microbeads were embedded in an injectable thermosensitive hydrogel matrix, which gels at skin temperature. The hydrogel fills and seals the wounds cavities, maintains high humidity at the wound area, absorbs exudate, and fixes microbeads, protecting them from direct contact with the harsh wound environment. In vitro investigations revealed that secretion of interleukin 10 (IL-0) and transforming growth factor β1 (TGF-β1) gene was gradually enhanced, providing a delivery platform for prolonged release of bioactive molecules. In vivo study on full-thickness wounds showed granulation and re-epithelialization, only after 7 days. Moreover, increased expression of α-smooth muscle actin (α-SMA) in the first 14 days after treatment ensured wound contraction. Besides, a gradual decrease in α-SMA secretion resulted in reduced scar formation. Well-organized collagen fibrils and high expression of the angiogenesis biomarker CD31 confirmed the promoting effect of the hydrogel on the wound-healing process. The proposed wound-dressing system would potentially be used in scalable and effective cell-based wound therapies.Intra-articular (IA) injection is an attractive route of administration for the treatment of osteoarthritis (OA). However, free drugs injected into the joint space are rapidly cleared and many of them can induce adverse off-target effects on different IA tissues. To overcome these limitations, we designed nanocomposite 4-arm-poly(ethylene glycol)-maleimide (PEG-4MAL) microgels, presenting cartilage- or synoviocyte-binding peptides, containing poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) as an IA small molecule drug delivery system. Microgels containing rhodamine B (model drug)-loaded PLGA NPs were synthesized using microfluidics technology and exhibited a sustained, near zero-order release of the fluorophore over 16 days in vitro. PEG-4MAL microgels presenting synoviocyte- or cartilage-targeting peptides specifically bound to rabbit and human synoviocytes or to bovine articular cartilage in vitro, respectively. Finally, using a rat model of post-traumatic knee OA, PEG-4MAL microgels were shown to be retained in the joint space for at least 3 weeks without inducing any joint degenerative changes as measured by EPIC-μCT and histology. Additionally, all microgel formulations were found trapped in the synovial membrane and significantly increased the IA retention time of a model small molecule near-infrared (NIR) dye compared to that of the free dye. These results suggest that peptide-functionalized nanocomposite PEG-4MAL microgels represent a promising intra-articular vehicle for tissue-localized drug delivery and prolonged IA drug retention for the treatment of OA.In this letter, we report the ability of the nanostructured aluminum Al 6063 alloy surfaces to inactivate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There was no recoverable viable virus after 6 h of exposure to the nanostructured surface, elucidating a 5-log reduction compared to a flat Al 6063 surface. The nanostructured surfaces were fabricated using wet-etching techniques which generated nanotextured, randomly aligned ridges approximately 23 nm wide on the Al 6063 alloy surfaces. In addition to the excellent mechanical resilience properties previously shown, the etched surfaces have also demonstrated superior corrosion resistance compared to the control surfaces. Such nanostructured surfaces have the potential to be used in healthcare environment such as hospitals and public spaces to reduce the surface transmission of SARS-CoV-2 and combat COVID-19.Chemotherapeutic delivery is limited by inefficient transport across cellular membranes. Here, we harness the cellular gap junction network to release therapeutic cargos directly into the cytosol. Specifically, cell-derived vesicles, termed connectosomes, contain gap junction transmembrane proteins that open a direct passageway to the cellular interior. Connectosomes were previously shown to substantially improve chemotherapeutic delivery in vitro. Here, we test connectosomes in vivo, using a murine breast tumor model. We demonstrate that connectosomes improve chemotherapeutic delivery to cellular targets within tumors by up to 16-fold, compared to conventional drug-loaded liposomes, suggesting an efficient alternative pathway for intracellular delivery.Polyethylene glycol-b-polylactic acid (PEG-PLA) and polyethylene glycol-b-poly(lactic-co-glycolic) acid) (PEG-PLGA) are two copolymers made up of three currently FDA approved polymers, used as drug delivery systems for specific indications. Here, the two were investigated to determine how they affected individual blood components and how they affected whole blood. Transmission and scanning electron microscopy imaging for each blood component and whole blood was completed with each amphiphilic copolymer for comparison. It was found that PEG-PLA does not disturb whole blood or its components, but PEG-PLGA harms platelets and plasma. These findings regarding PEG-PLGA show that this material is not compliant with all current FDA standards and could explain why clinical trials are facing complications.Chemodynamic therapy (CDT) has aroused extensive attention for cancer treatment in the last five years, as it could suppress tumor progression through in situ detrimental oxidative stress of the tumor cells via the Fenton reaction. Under a tumor acidic microenvironment, the Fenton reaction can be initiated for disproportioning endogenous hydrogen peroxide into highly toxic hydroxyl radical. Taking advantage of the highly tumor-specific therapy modality, various Fenton nanocatalysts have been developed for CDT. In particular, iron-containing Fenton nanocatalysts with minimal cytotoxicity exhibit great promise for clinical translation. In this review, we summarize the recent progress of CDT based on iron-containing nanomaterials, including iron oxide nanoparticles, glassy iron nanoclusters, ferrocene nanoparticles, metal polyphenol networks, metal-organic frameworks, etc. We also discuss the challenges and perspectives for promoting CDT by rational design of iron-containing nanomaterials, highlighting their potential for precise cancer therapy.Over the past few decades, tremendous progress has been made in the development of engineering nanomaterials, which opened new horizons in the field of diagnosis and treatment of various diseases. Selleckchem SCH772984 In particular, self-assembled organic nanomaterials with intriguing features including delicate structure tailoring, facile processability, low cost, and excellent biocompatibility have shown outstanding potential in biomedical applications because of the enhanced permeability and retention (EPR) effect and multifunctional properties. In this review, we briefly introduce distinctive merits of self-assembled organic nanomaterials for biomedical applications. The main focus will be placed on summarizing recent advances in self-assembled organic nanomedicine for drug delivery, bioimaging, and cancer phototherapy, followed by highlighting a critical perspective on further development of self-assembled organic nanomaterials for future clinical translation. We believe that the above themes will appeal to researchers from different fields, including material, chemical, and biological sciences, as well as pharmaceutics.