Development of a Composite Hydrogel Containing Statistically Optimized PDGF-Loaded Polymeric Nanospheres for Skin Regeneration: In Vitro Evaluation and Stem Cell Differentiation Studies.

Platelet-derived growth factor-BB (PDGF-BB) is a polypeptide growth factor generated by platelet granules faced to cytokines. It plays a role in forming and remodeling various tissue types, including epithelial tissue, through interaction with cell-surface receptors on most mesenchymal origin cells. However, it breaks down quickly in biological fluids, emphasizing the importance of preserving them from biodegradation. To address this challenge, we formulated and evaluated PDGF-encapsulated nanospheres (PD@PCEC) using polycaprolactone-polyethylene glycol-polycaprolactone. PD@PCECs were fabricated through the triple emulsion methodology and optimized by using the Box-Behnken design. The encapsulation efficiency (EE) of nanoencapsulated PDGF-BB was investigated concerning four variables: stirring rate (X1), stirring duration (X2), poly(vinyl alcohol) concentration (X3), and PDGF-BB concentration (X4). The selected optimized nanospheres were integrated into a gelatin-collagen scaffold (PD@PCEC@GC) and assessed for morphology, biocompatibility, in vitro release, and differentiation-inducing activity in human adipose-derived stem cells (hADSCs). The optimized PD@PCEC nanospheres exhibited a particle size of 177.9 ± 91 nm, a zeta potential of 5.2 mV, and an EE of 87.7 ± 0.44%. The release profile demonstrated approximately 85% of loaded PDGF-BB released during the first 360 h, with a sustained release over the entire 504 h period, maintaining bioactivity of 87.3%. The study also included an evaluation of the physicochemical properties of the scaffolds and an assessment of hADSC adhesion to the scaffold's surface. Additionally, hADSCs cultivated within the scaffold effectively differentiated into keratinocyte-like cells (KLCs) over 21 days, evidenced by morphological changes and upregulation of keratinocyte-specific genes, including cytokeratin 18, cytokeratin 19, and involucrin, at both transcriptional and protein levels.

Effects of chitosan and TiO2 nanoparticles on the antibacterial property and ability to self-healing of cracks and retrieve mechanical characteristics of dental composites.

The aim of this study was to improve the self-healing properties of dental nanocomposite using nanoparticles of TiO2 and chitosan. We evaluated flexural and compressive strength, crack-healing, and self-healing lifespan after 3 months of water aging. The effect of the developed composite on cell viability and toxicity was assessed by an MTT assay on human alveolar basal epithelial cells (A549 cell line). The nanocomposite included 7.5 wt% polyurea-formaldehyde (PUF) and 0, 0.5, and 1 wt% n-TiO2 and chitosan. After the fracture, the samples were put in a mold for 1-90 days to enable healing. Then, the fracture toughness of the healed nanocomposites and the healing yield were measured. The flexural strength of the nanocomposite improved by adding 0.5 wt% n-TiO2, while the compressive strength increased after adding 0.5 wt% chitosan (p > 0.1). When these two materials were used simultaneously, the flexural strength was improved by around 2%; however, the compressive strength was unaffected. Compared to the other sample, the nanocomposite with 0.5 wt% n-TiO2 and chitosan had higher KIC-healing and self-healing efficiency. Self-healing efficacy had no significant effect of water aging over 90 days compared to one day (p > 0.1), demonstrating that the PUF nanocapsules were not damaged.

Folate receptor-mediated delivery system based on chitosan coated polymeric nanoparticles for combination therapy of breast cancer.

Combination therapy using two or more drugs with different mechanisms of action is an effective strategy for treating cancer. This is because of the synergistic effect of complementary drugs that enhances their effectiveness. However, this approach has some limitations, such as non-specific distribution of the drugs in the tumor and the occurrence of dose-dependent toxicity to healthy tissues. To overcome these issues, we have developed a folate receptor-mediated co-delivery system that improves the access of chemotherapy drugs to the tumor site. We prepared a nanoplatform by encapsulating paclitaxel (PTX) and curcumin (CUR) in poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) co-polymer using a double emulsion method and coating nanoparticles with pH-responsive chitosan-folic acid (CS-FA) conjugate. The nanocarrier's physicochemical properties were studied, confirming successful preparation with appropriate size and morphology. PTX and CUR could be released synchronously in a controlled and acid-facilitated manner. The dual drug-loaded nanocarrier exhibited excellent anti-tumor efficiency in MDA-MB-231 cells in vitro. The active targeting effect of FA concluded from the high inhibitory effect of dual drug-loaded nanocarrier on MDA-MB-231 cells, which have overexpressed folate receptors on their surface, compared to Human umbilical vein endothelial cells (HUVEC). Overall, the nanoengineered folate receptor-mediated co-delivery system provides great potential for safe and effective cancer therapy.

A Systematic Review of Stem Cell Differentiation into Keratinocytes for Regenerative Applications.

To improve wound healing or treatment of other skin diseases, and provide model cells for skin biology studies, in vitro differentiation of stem cells into keratinocyte-like cells (KLCs) is very desirable in regenerative medicine. This study examined the most recent advancements in in vitro differentiation of stem cells into KLCs, the effect of biofactors, procedures, and preparation for upcoming clinical cases. A range of stem cells with different origins could be differentiated into KLCs under appropriate conditions. The most effective ways of stem cell differentiation into keratinocytes were found to include the co-culture with primary epithelial cells and keratinocytes, and a cocktail of growth factors, cytokines, and small molecules. KLCs should also be supported by biomaterials for the extracellular matrix (ECM), which replicate the composition and functionality of the in vivo extracellular matrix (ECM) and, thus, support their phenotypic and functional characteristics. The detailed efficient characterization of different factors, and their combinations, could make it possible to find the significant inducers for stem cell differentiation into epidermal lineage. Moreover, it allows the development of chemically known media for directing multi-step differentiation procedures.In conclusion, the differentiation of stem cells to KLCs is feasible and KLCs were used in experimental, preclinical, and clinical trials. However, the translation of KLCs from in vitro investigational system to clinically valuable cells is challenging and extremely slow.

Chrysin and chrysin-loaded nanocarriers induced immunogenic cell death on B16 melanoma cells.

Induction of immunogenic cell death (ICD) is a promising strategy for cancer immunotherapy. Chrysin, which has potential anticancer effects, faces limitations in clinical applications due to its poor water solubility. This study aimed to formulate chrysin with PEG-poly(α-benzylcarboxylate-ε-caprolactone) (PBCL) nanoparticles (NPs) and assess their anticancer and ICD-inducing potency in melanoma cells, comparing with free chrysin. The co-solvent evaporation method was employed to develop chrysin-loaded NPs. UV spectroscopy, dynamic light scattering, and the dialysis bag method were used to evaluate the encapsulation efficiency (EE), particle size, polydispersity index (PDI), and drug release profile, respectively. The anticancer effects of the drugs were assessed using the MTT and trypan blue exclusion assays. Flow cytometry was employed to evaluate apoptosis and calreticulin (CRT) expression. ELISA and western blotting were used to detect heat shock protein 90 (HSP90), Annexin A1, GRP78 (Glucose-related protein78), and activated protein kinase R-like endoplasmic reticulum kinase (p-PERK). Chrysin-loaded PEG-PBCL NPs (chrysin-PEG-PBCL) showed an EE of 97 ± 1%. Chrysin-PEG-PBCL was 38.18 ± 3.96 nm in size, with a PDI being 0.62 ± 0.23. Chrysin-PEG-PBCL showed an initial burst release, followed by sustained release over 24 h. Chrysin-PEG-PBCL exhibited a significantly stronger anticancer effect in B16 cells. Chrysin-PEG-PBCL was found to be more potent in inducing apoptosis. Both free chrysin and chrysin NPs induced ICD as indicated by an increase in the levels of ICD biomarkers. Interestingly, chrysin NPs were found to be more potent inducers of ICD than the free drug. These findings demonstrate that chrysin and chrysin-PEG-PBCL NPs can induce ICD in B16 cells. PEG-PBCL NPs significantly enhanced the potency of chrysin in inducing ICD compared to its free form.

Injectable hydrogels for cartilage and bone tissue regeneration: A review.

Annually, millions of patients suffer from irreversible injury owing to the loss or failure of an organ or tissue caused by accident, aging, or disease. The combination of injectable hydrogels and the science of stem cells have emerged to address this persistent issue in society by generating minimally invasive treatments to augment tissue function. Hydrogels are composed of a cross-linked network of polymers that exhibit a high-water retention capacity, thereby mimicking the wet environment of native cells. Due to their inherent mechanical softness, hydrogels can be used as needle-injectable stem cell carrier materials to mend tissue defects. Hydrogels are made of different natural or synthetic polymers, displaying a broad portfolio of eligible properties, which include biocompatibility, low cytotoxicity, shear-thinning properties as well as tunable biological and physicochemical properties. Presently, novel ongoing developments and native-like hydrogels are increasingly being used broadly to improve the quality of life of those with disabling tissue-related diseases. The present review outlines various future and in-vitro applications of injectable hydrogel-based biomaterials, focusing on the newest ongoing developments of in-situ forming injectable hydrogels for bone and cartilage tissue engineering purposes.

PCL-based nanoparticles for doxorubicin-ezetimibe co-delivery: A combination therapy for prostate cancer using a drug repurposing strategy.

Introduction: Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment. Methods: In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures. Results: The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells. Conclusion: Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.

Natural and synthetic nanovectors for cancer therapy.

Nanomaterials have been extensively studied in cancer therapy as vectors that may improve drug delivery. Such vectors not only bring numerous advantages such as stability, biocompatibility, and cellular uptake but have also been shown to overcome some cancer-related resistances. Nanocarrier can deliver the drug more precisely to the specific organ while improving its pharmacokinetics, thereby avoiding secondary adverse effects on the not target tissue. Between these nanovectors, diverse material types can be discerned, such as liposomes, dendrimers, carbon nanostructures, nanoparticles, nanowires, etc., each of which offers different opportunities for cancer therapy. In this review, a broad spectrum of nanovectors is analyzed for application in multimodal cancer therapy and diagnostics in terms of mode of action and pharmacokinetics. Advantages and inconveniences of promising nanovectors, including gold nanostructures, SPIONs, semiconducting quantum dots, various nanostructures, phospholipid-based liposomes, dendrimers, polymeric micelles, extracellular and exome vesicles are summarized. The article is concluded with a future outlook on this promising field.

Thermosensitive and biodegradable PCL-based hydrogels: potential scaffolds for cartilage tissue engineering.

Due to a lack of sufficient blood supply and unique physicochemical properties, the treatment of injured cartilage is laborious and needs an efficient strategy. Unfortunately, most of the current therapeutic approaches are, but not completely, unable to restore the function of injured cartilage. Tissue engineering-based modalities are an alternative option to reconstruct the injured tissue. Considering the unique structure and consistency of cartilage tissue (osteochondral junction), it is mandatory to apply distinct biomaterials with unique properties slightly different from scaffolds used for soft tissues. PCL is extensively used for the fabrication of fine therapeutic scaffolds to accelerate the restorative process. Thermosensitive PCL hydrogels with distinct chemical compositions have paved the way for sophisticated cartilage regeneration. This review aimed to collect recent findings regarding the application of PCL in hydrogels blended with natural, synthetic materials in the context of cartilage healing.

Preparation and Antiproliferative Activity Evaluation of Juglone-Loaded BSA Nanoparticles.

Purpose: Today, the discovery of novel and effective chemotherapeutic compounds is the main challenge in cancer therapy. In recent years, the anti-tumoral activity of natural naphthoquinone juglone (JUG), present in different parts of walnut trees, has received considerable interest. The purpose of the current study was to prepare and evaluate the in vitro antiproliferative activity of JUG-loaded bovine serum albumin nanoparticles (JUG-BSA NPs). Methods: BSA NPs and JUG-BSA NPs were prepared using the desolvation technique. The NPs were characterized for their particle size (PS), zeta potential (ZP), drug loading (DL) capacity and encapsulation efficiency (EE). The anti-proliferative activity of JUG-BSA NPs was evaluated on A431 and HT29 cancer cell lines using cellular uptake and MTT assays. Results: The PS and ZP values of JUG-BSA NPs were 85 ± 6.55 nm and -29.6 mV, respectively. The DL capacity and EE were 3.7% to 5% and 50.4% to 94.6%, respectively. The cytotoxicity of JUG-BSA NPs was significantly less on both cultured A431 and HT29 cells at the studied concentrations when compared to free JUG. However, the effect was not very substantial, particularly at high levels. Conclusion: In conclusion, BSA NPs can be used as a suitable and safe carrier for the delivery of JUG, a cytotoxic hydrophobic natural compound.

Synthesis and Characterization of a Novel Dual-Responsive Nanogel for Anticancer Drug Delivery.

In this study, to reduce the side effects of anticancer drugs and also to increase the efficiency of current drug delivery systems, a pH and temperature-responsive polymeric nanogel was synthesized by copolymerization of N-vinylcaprolactam (VCL) and acrylic acid (AA) monomers (P(VCL-co-AA)) with a novel cross-linker, triethylene glycol dimethacrylate (TEGDMA), as a biocompatible and nontoxic component. The structural and physicochemical features of the P(VCL-co-AA) nanogel were characterized by FT-IR, DLS/Zeta potential, FE-SEM, and 1HNMR techniques. The results indicated that spherical polymeric nanogel was successfully synthesized with a 182 nm diameter. The results showed that the polymerization process continues with the opening of the carbon-carbon double bond of monomers, which was approved by C-C band removing located at 1600 cm-1. Doxorubicin (Dox) as a chemotherapeutic agent was loaded into the P(VCL-co-AA), whit a significant loading of Dox (83%), and the drug release profile was investigated in the physiological and cancerous site simulated conditions. P(VCL-co-AA) exhibited a pH and temperature-responsive behavior, with an enhanced release rate in the cancerous site condition. The biocompatibility and nontoxicity of P(VCL-co-AA) were approved by MTT assay on the normal human foreskin fibroblasts-2 (HFF-2) cell line. Also, Dox-loaded P(VCL-co-AA) had excellent toxic behavior on the Michigan Cancer Foundation-7 (MCF-7) cell line as model cancerous cells. Moreover, Dox-loaded P(VCL-co-AA) had higher toxicity in comparison with free Dox, which would be a vast advantage in reducing Dox side effects in the clinical cancer treatment applications.

Immune checkpoint blockade in melanoma: Advantages, shortcomings and emerging roles of the nanoparticles.

The early stages of melanoma could be treated promisingly by surgical resection; however, the challenge is in advanced cases in which targeted therapy could be an option. The expression of immune checkpoints such as CTLA-4, PD-1, PD-L1, TIM-3, LAG-3, and VISTA is at adequate levels in the melanoma tumor microenvironment (TME) implying the promising outcomes of applying immune checkpoint blockades (ICBs). Since the first Food and Drug Administration (FDA) approved ICB, ipilimumab, in melanoma patients, the treatment of melanoma patients with ICBs resulted in improved survival rate and anti-tumor responses, making ICB one of the promising therapeutic approaches. However, due to high biodistribution, these drugs could non-specifically target healthy cells and empower the immune reactions out of control, which results in the incidence of immune-related adverse events. Although there are development management approaches, a new emerging platform is recently available with aid of drug delivery strategies, particularly nanoparticles (NPs). Here, we investigated the recent trials of ICBs in the context of melanoma cases while showing the challenges of this approach. Also, the application of NPs in order to locally deliver ICBs in melanoma tumor models is discussed.

Synthesis and characterization of growth factor free nanoengineered bioactive scaffolds for bone tissue engineering.

BACKGROUND: To address the obstacles that come with orthopedic surgery for biological graft tissues, including immune rejections, bacterial infections, and weak osseointegration, bioactive nanocomposites have been used as an alternative for bone grafting since they can mimic the biological and mechanical properties of the native bone. Among them, PCL-PEG-PCL (PCEC) copolymer has gained much attention for bone tissue engineering as a result of its biocompatibility and ability for osteogenesis. METHODS: Here, we designed a growth factor-free nanoengineered scaffold based on the incorporation of Fe3O4 and hydroxyapatite (HA) nanoparticles into the PCL-PEG-PCL/Gelatin (PCEC/Gel) nanocomposite. We characterized different formulations of nanocomposite scaffolds in terms of physicochemical properties. Also, the mechanical property and specific surface area of the prepared scaffolds, as well as their feasibility for human dental pulp stem cells (hDPSCs) adhesion were assessed. RESULTS: The results of in vitro cell culture study revealed that the PCEC/Gel Fe3O4&HA scaffold could promote osteogenesis in comparison with the bare scaffold, which confirmed the positive effect of the Fe3O4 and HA nanoparticles in the osteogenic differentiation of hDPSCs. CONCLUSION: The incorporation of Fe3O4 and HA with PCEC/gelatin could enhance osteogenic differentiation of hDPSCs for possible substitution of bone grafting tissue.

Gentamycin-loaded halloysite-based hydrogel nanocomposites for bone tissue regeneration: fabrication, evaluation of the antibacterial activity and cell response.

Biocompatible hydrogels are promising approaches for bone repair and engineering. A novel therapeutic nanocomposite hydrogel was designed based on triblock copolymer poly e-caprolactone (PCL)-polyethylene glycol-PCL and natural gelatin (PCEC/GEL) and reinforced with halloysite nanotube (HNT). Gentamicin (GM) loaded HNT was immobilized in polymeric hydrogel matrix to fabricate scaffolds using the freeze-drying method. Scaffolds were characterized via Fourier transform infrared (FT-IR), x-ray powder diffraction, and scanning electron microscope (SEM) methods. The swelling ratio, density, porosity, degradation, and mechanical behavior were evaluated to investigate the effects of HNT on the physicochemical properties of the composite. Cell viability and cell attachment were investigated by microculture tetrazolium (MTT) assay and SEM. Cell proliferation was observed without any cytotoxicity effect on human dental pulp-derived mesenchymal stem cells (h-DPSCs). Alizarin red staining and real-time reverse transcription polymerase chain reaction (QRT-PCR) assay were carried out to monitor the osteoconductivity of scaffolds on h-DPSCs which were seeded drop wise onto the top of scaffolds. The quantification of the messenger RNA (mRNA) expression of osteogenic marker genes, bone morphogenetic protein 2, SPARK, bone gamma-carboxyglutamate protein and runt-related transcription factor 2 over a period of 21 d of cell seeding, demonstrated that cell-encapsulating PCEC/GEL/HNT-GM hydrogel scaffolds supported osteoblast differentiation of h-DPSCs into osteogenic cells through the up-regulation of related genes along with moderate effects on cell viability. Moreover, the antibiotics loading reduced bacterial growth while maintaining the osteogenic properties of the scaffold. Therefore, the bactericidal PCEC/GEL/HNT-GM hydrogel nanocomposite, with enhanced durability, maintenance the functionality of seeded cellsin vitrothat can be a remarkable dual-functional candidate for hard tissue reconstruction and customized bone implants fabrication via the direct incorporation of bactericidal drug to prevent infection.

Magnetite and bismuth sulfide Janus heterostructures as radiosensitizers for in vivo enhanced radiotherapy in breast cancer.

Janus heterostructures based on bimetallic nanoparticles have emerged as effective radiosensitizers owing to their radiosensitization capabilities in cancer cells. In this context, this study aims at developing a novel bimetallic nanoradiosensitizer, Bi2S3-Fe3O4, to enhance tumor accumulation and promote radiation-induced DNA damage while reducing adverse effects. Due to the presence of both iron oxide and bismuth sulfide metallic nanoparticles in these newly developed nanoparticle, strong radiosensitizing capacity is anticipated through the generation of reactive oxygen species (ROS) to induce DNA damage under X-Ray irradiation. To improve blood circulation time, biocompatibility, colloidal stability, and tuning surface functionalization, the surface of Bi2S3-Fe3O4 bimetallic nanoparticles was coated with bovine serum albumin (BSA). Moreover, to achieve higher cellular uptake and efficient tumor site specificity, folic acid (FA) as a targeting moiety was conjugated onto the bimetallic nanoparticles, termed Bi2S3@BSA-Fe3O4-FA. Biocompatibility, safety, radiation-induced DNA damage by ROS activation and generation, and radiosensitizing ability were confirmed via in vitro and in vivo assays. The administration of Bi2S3@BSA-Fe3O4-FA in 4T1 breast cancer murine model upon X-ray radiation revealed highly effective tumor eradication without causing any mortality or severe toxicity in healthy tissues. These findings offer compelling evidence for the potential capability of Bi2S3@BSA-Fe3O4-FA as an ideal nanoparticle for radiation-induced cancer therapy and open interesting avenues of future research in this area.

The fabrication of halloysite nanotube-based multicomponent hydrogel scaffolds for bone healing.

Bone tissue engineering, as an alternative for common available therapeutic approaches, has been developed to focus on reconstructing of the missing tissues and restoring their functionality. In this work, three-dimensional (3D) nanocomposite scaffolds of polycaprolactone-polyethylene glycol-polycaprolactone/gelatin (PCEC/Gel) were prepared by freeze-drying method. Biocompatible nanohydroxyapatite (nHA), iron oxide nanoparticle (Fe3O4) and halloysite nanotube (HNT) powders were added to the polymer matrix aiming to combine the osteogenic activity of nHA or Fe3O4 with high mechanical strength of HNT. The scanning electron microscope (SEM) methods was utilized to characterize the nanotube morphology of HNT as well as nanoparticles of Fe3O4 and nHA. Prepared scaffolds were characterized via Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), and SEM methods. In addition, the physical behavior of scaffolds was evaluated to explore the influence of HNT on the physicochemical properties of composites. Cell viability and attachment were investigated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and SEM on human dental pulp-derived mesenchymal stem cells (h-DPSCs) in-vitro. Cell proliferation was observed without any cytotoxicity effect on h-DPSCs for all examined scaffolds. Alizarin red (ARS) and alkaline phosphatase (ALP) staining were carried out to determine the osteoconductivity of scaffolds. The data demonstrated that all PCEC/Gel/HNT hydrogel scaffolds supported osteoblast differentiation of hDPSCs with moderate effects on cell proliferation. Moreover, PCEC/Gel/HNT/nHA with proper mechanical strength showed better biological activity compared to PCEC/Gel/HNT/Fe3O4 and PCEC/Gel/HNT scaffolds. Therefore, this study suggested that with proper fillers content, PCEC/Gel/HNT nanocomposite hydrogels alone or in a complex with nHA, Fe3O4 could be a suitable candidate for hard tissue regeneration.

Enhancing the function of PLGA-collagen scaffold by incorporating TGF-ß1-loaded PLGA-PEG-PLGA nanoparticles for cartilage tissue engineering using human dental pulp stem cells.

Since cartilage has a limited capacity for self-regeneration, treating cartilage degenerative disorders is a long-standing difficulty in orthopedic medicine. Researchers have scrutinized cartilage tissue regeneration to handle the deficiency of cartilage restoration capacity. This investigation proposed to compose an innovative nanocomposite biomaterial that enhances growth factor delivery to the injured cartilage site. Here, we describe the design and development of the biocompatible poly(lactide-co-glycolide) acid-collagen/poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA-collagen/PLGA-PEG-PLGA) nanocomposite hydrogel containing transforming growth factor-ß1 (TGF-ß1). PLGA-PEG-PLGA nanoparticles were employed as a delivery system embedding TGF-ß1 as an articular cartilage repair therapeutic agent. This study evaluates various physicochemical aspects of fabricated scaffolds by 1HNMR, FT-IR, SEM, BET, and DLS methods. The physicochemical features of the developed scaffolds, including porosity, density, degradation, swelling ratio, mechanical properties, morphologies, BET, ELISA, and cytotoxicity were assessed. The cell viability was investigated with the MTT test. Chondrogenic differentiation was assessed via Alcian blue staining and RT-PCR. In real-time PCR testing, the expression of Sox-9, collagen type II, and aggrecan genes was monitored. According to the results, human dental pulp stem cells (hDPSCs) exhibited high adhesion, proliferation, and differentiation on PLGA-collagen/PLGA-PEG-PLGA-TGFß1 nanocomposite scaffolds compared to the control groups. SEM images displayed suitable cell adhesion and distribution of hDPSCs throughout the scaffolds. RT-PCR assay data displayed that TGF-ß1 loaded PLGA-PEG-PLGA nanoparticles puts forward chondroblast differentiation in hDPSCs through the expression of chondrogenic genes. The findings revealed that PLGA-collagen/PLGA-PEG-PLGA-TGF-ß1 nanocomposite hydrogel can be utilized as a supportive platform to support hDPSCs differentiation by implementing specific physio-chemical features.

How Advancing are Mesoporous Silica Nanoparticles? A Comprehensive Review of the Literature.

The application of mesoporous silica nanoparticles (MSNs) is ubiquitous in various sciences. MSNs possess unique features, including the diversity in manufacturing by different synthesis methods and from different sources, structure controllability, pore design capabilities, pore size tunability, nanoparticle size distribution adjustment, and the ability to create diverse functional groups on their surface. These characteristics have led to various types of MSNs as a unique system for drug delivery. In this review, first, the synthesis of MSNs by different methods via using different sources were studied. Then, the parameters affecting their physicochemical properties and functionalization have been discussed. Finally, the last decade's novel strategies, including surface functionalization, drug delivery, and cancer treatment, based on the MSNs in drug delivery and cancer therapy have been addressed.

Recent scaffold-based tissue engineering approaches in premature ovarian failure treatment.

Recently, tissue engineering and regenerative medicine have received significant attention with outstanding advances. The main scope of this technology is to recover the damaged tissues and organs or to maintain and improve their function. One of the essential fields in tissue engineering is scaffold designing and construction, playing an integral role in damaged tissues reconstruction and repair. However, premature ovarian failure (POF) is a disorder causing many medical and psychological problems in women. POF treatment using tissue engineering and various scaffold has recently made tremendous and promising progress. Due to the importance of the subject, we have summarized the recently examined scaffolds in the treatment of POF in this review.

A critical review of fibrous polyurethane-based vascular tissue engineering scaffolds.

Certain polymeric materials such as polyurethanes (PUs) are the most prevalent class of used biomaterials in regenerative medicine and have been widely explored as vascular substitutes in several animal models. It is thought that PU-based biomaterials possess suitable hemo-compatibility with comparable performance related to the normal blood vessels. Despite these advantages, the possibility of thrombus formation and restenosis limits their application as artificial functional vessels. In this regard, various surface modification approaches have been developed to enhance both hemo-compatibility and prolong patency. While critically reviewing the recent advances in vascular tissue engineering, mainly PU grafts, this paper summarizes the application of preferred cell sources to vascular regeneration, physicochemical properties, and some possible degradation mechanisms of PU to provide a more extensive perspective for future research.