Yuelong wang

Injectable thermosensitive hydrogel composite with surface-functionalized calcium phosphate as raw materials

In this study, L-lactide was used to modify the tricalcium phosphate (β-TCP) and tetracalcium phosphate (TTCP) surface which can form functionalized poly(l-lactic acid) (PLLA)-grafted β-TCP (g-β-TCP) and PLLA-grafted TTCP (g-TTCP) particles. The g-β-TCP and g-TTCP obtained were incorporated into a PEG-PCL-PEG (PECE) matrix to prepare injectable thermosensitive hydrogel composites. The morphology of the hydrogel composites showed that the g-β-TCP and g-TTCP particles dispersed homogeneously into the polymer matrix, and each hydrogel composite had a three-dimensional network structure. Rheologic analysis showed that the composite had good thermosensitivity. Changes in calcium concentration and pH in simulated body fluid solutions confirmed the feasibility of surface-functionalized calcium phosphate for controlled release of calcium. All the results indicate that g-β-TCP/PECE and g-TTCP/PECE hydrogels might be a promising protocol for tissue engineering.

Preparation and characterization of polylactide/poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) hybrid fibers for potential application in bone tissue engineering

The aim of this study was to develop a kind of osteogenic biodegradable composite graft consisting of human placenta-derived mesenchymal stem cell (hPMSC) material for site-specific repair of bone defects and attenuation of clinical symptoms. The novel nano- to micro-structured biodegradable hybrid fibers were prepared by electrospinning. The characteristics of the hybrid membranes were investigated by a range of methods, including Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Morphological study with scanning electron microscopy showed that the average fiber diameter and the number of nanoscale pores on each individual fiber surface decreased with increasing concentration of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC). The prepared polylactide (PLA)/PCEC fibrous membranes favored hPMSC attachment and proliferation by providing an interconnected, porous, three-dimensional mimicked extracellular environment. What is more, hPMSCs cultured on the electrospun hybrid PLA/PCEC fibrous scaffolds could be effectively differentiated into bone-associated cells by positive alizarin red staining. Given the good cellular response and excellent osteogenic potential in vitro, the electrospun PLA/PCEC fibrous scaffolds could be one of the most promising candidates for bone tissue engineering.

Fabrication and in vivo chondrification of a poly(propylene carbonate)/L-lactide-grafted tetracalcium phosphate electrospun scaffold for cartilage tissue engineering

Regenerative therapies that utilize stem cell differentiation in three-dimensional porous scaffolds have attracted significant interest in recent years. In this study, fibrous poly(propylene carbonate)/poly(L-lactic acid)-grafted tetracalcium phosphate (PPC/g-TTCP) scaffolds were prepared using an electrospinning method. The characteristics of the fabricated scaffolds were investigated using scanning electron microscopy, differential scanning calorimetry, thermogravimetric analyses, Fourier transform infrared spectroscopy, X-ray diffraction analyses, water contact angle measurements and tensile tests. Due to the importance of biocompatibility, rat bone marrow-derived stem cells were cultured on the scaffolds, and the cell proliferation was investigated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays. Subsequently, chondrogenic differentiation was induced in these cells in vitro and in vivo. Fourteen days later, chondrocyte-like cells had developed on the PPC/g-TTCP scaffolds, as evidenced by the accumulation of glycosaminoglycan and type II collagen. After subcutaneous transplantation into nude mice, a typical cartilage cell morphology was observed on the scaffolds. These findings suggest that PPC/g-TTCP scaffolds can support cartilage development and are excellent candidate scaffolds for cartilage defect repair.

Novel nanoscale topography on poly(propylene carbonate)/poly(ε-caprolactone) electrospun nanofibers modifies osteogenic capacity of ADCs

In this study, we electrospun novel poly(propylene carbonate)/poly(e-caprolactone) (PPC/PCL) nanofibers with a special nanoscale topography using a simple process. The characteristics of the fabricated scaffolds were investigated using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction analyses (XRD), thermogravimetric analyses (TG), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), water contact angle measurements (WCA), tensile tests and Brunauer–Emmett–Teller (BET) surface area analysis. To determine whether the nanoscale topography altered mesenchyme stem cell adhesion proliferation and differentiation behavior, adipose tissue-derived stromal cells (ADCs) were cultured on pure PPC electrospun scaffolds with smooth nanotopography and PPC/PCL (20 wt% PCL) hybrid scaffold with nanoscale topography. The results reveal that PPC/PCL electrospun fibers with special inter-surface-connected pores possess a high BET surface area and could promote ADCs adhesion and proliferation. According to alizarin red S staining and von-Kossa staining assays, there are more calcium nodule deposits on scaffolds with inter-surface-connected pores.

Docetaxel load biodegradable porous microspheres for the treatment of colorectal peritoneal carcinomatosis.

Micro- and nanoparticle formulations are widely used to improve the bioavailability of low solubility drugs. In this study, biodegradable poly(L-lactide acid)-Pluronic L121-poly(L-lactide acid) (PLLA-L121-PLLA) was developed. And then a controlled drug delivery system (CDDS), docetaxel (DOC) loaded PLLA-L121-PLLA porous microsphere (DOC MS) was prepared for colorectal peritoneal carcinomatosis (CRPC) therapy. DOC MS was prepared by DOC and PLLA-L121-PLLA using an oil-in-water emulsion solvent evaporation method. The particle size, morphological characteristics, encapsulation efficiency, in vitro drug release studies and in vitro cytotoxicity of DOC MS have been investigated. In vitro release profile demonstrated a significant difference between rapid release of free DOC and much slower and sustained release of DOC MS. Furthermore, cytotoxicity assay indicated cytotoxicity was increased after DOC was encapsulated into polymeric microspheres. In addition, intraperitoneal administration of DOC MS could effectively suppress growth and metastasis of CT26 peritoneal carcinomatosis in vivo, and prolonged the survival of tumor bearing mice. Immunohistochemistry staining of tumor tissues with Ki-67 revealed that DOC MS induced a stronger anti-tumor effect by increasing apoptosis of tumor cells in contrast to other groups (P<0.05). Thus, our results suggested that DOC MS may have great potential applications in clinic.

Facile electrospinning of an efficient drug delivery system

ABSTRACT Introduction: Electrospinning is a facile method for fabricating fibers with diameters in the order of several nanometers to a few micrometers. This technology has great potential for preparing drug delivery systems (DDSs) and has received a great deal of attention in recent years. When combined with certain nanocarriers, such as micelles, nanoparticles or vesicles, an electrospun fiber membrane becomes an efficient and helpful platform for the above-mentioned formulations to achieve sustained and targeted drug release. Areas covered: The developmental process of electrospinning technology is briefly summarized and the drugs and the materials electrospun into drug delivery systems are listed . The application of electrospinning technology in the biomedical field and its current progress are emphasized. Expert opinion: A safe, efficient and multifunctional electrospinning drug delivery system is urgently needed, which requires further studies. Cross-disciplinary strategies that cover pharmaceutical science, material science and computer science may provide guidance in bringing electrospinning technology in drug delivery to fruition.

Nanofibers for improving the wound repair process: the combination of a grafted chitosan and an antioxidant agent

Wound healing, a complex process involving several important biomolecules and pathways, requires efficient dressings to enhance the therapy effects. Electrospinning nanofiber mats for wound healing have attracted significant interest because of their unique properties including ultrathin diameters, high volume ratios, and three-dimensional structure that mimics the extracellular matrix. In this study, we synthesized grafted chitosans with improved solubility, resulting in circumventing the use of acidic solvents, such as acetic acid and trifluoroacetic acid, simplified the electrospinning processes and fabricated poly(vinyl alcohol)-free nanofibers. The model drug curcumin was encapsulated in the nanofibers, consisting of grafted chitosan and poly(propylene carbonate), by electrospinning, which gradually released the drug from the matrix in 288 hours. Moreover, the curcumin-loaded composite nanofibers showed excellent free-radical scavenging capabilities. The enhanced wound healing efficacy was confirmed by an in vivo test and approximately 100% wound closure ratio was observed in the 10% curcumin-loaded PPC/g-CS nanofibers group at day 21 post surgery, which was subsequently evidenced by haematoxylin and eosin stain and Massons trichrome stain. Higher granulation scores and higher collagen contents were observed in the PPC/g-CS 10% curcumin group, showing significant differences among all the groups. These results demonstrated that the combination of grafted chitosan and curcumin improved the wound healing process. Moreover, electrospinning nanofibers based on the grafted polymer and curcumin showed potential for wound repair applications.

In situ gel-forming dual drug delivery system for synergistic combination therapy of colorectal peritoneal carcinomatosis

Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis of intra-abdominal cancers, occurring in as many as 50% of colon cancer patients, and is associated with a poor prognosis. For the treatment of CRPC, cytoreductive surgery alone is inadequate at the microscopic level, and systemic chemotherapy has a limited effect due to the peritoneal-plasma barrier. Intraperitoneal chemotherapy is logically proposed early after surgery to treat the residual small and microscopic tumors. Traditional chemotherapy is typically infused intravenously. However, intraperitoneal chemotherapy allows direct contact of anti-cancer agents with tumor cells, which could improve tumor regression efficacy and minimize systemic toxicity. Furthermore, injectable and thermosensitive polymer hydrogels have shown promising applications as controlled drug delivery systems for in situ chemotherapy. In this study, a biodegradable thermogelling block copolymer poly(L-lactide acid)–Pluronic L35–poly(L-lactide acid) (PLLA–L35–PLLA) was synthesized to fabricate a novel local drug delivery system (DOC-M/OXA-H) composed of docetaxel loaded micelles (DOC-M) and an oxaliplatin loaded hydrogel (OXA-H). DOC, a widely used anticancer drug with extremely high hydrophobicity, was loaded into the biodegradable copolymer micelles by the membrane dialysis method without using any surfactants or excipients. And DOC-M was encapsulated in OXA-H to achieve the aim of synergistic combination therapy with significantly high efficacy and good patient compliance. As a result, DOC-M/OXA-H was an injectable flowing sol at ambient temperature and became a solid-like gel at physiological temperature without any crosslinking agent. Meanwhile, DOC-M/OXA-H demonstrated a slow and sustained drug release profile and the combination therapy of DOC and OXA exhibited quite potent cytotoxicity in vitro. Furthermore, an in vivo antitumor test with CRPC-bearing mice suggested that DOC-M/OXA-H was more competent for suppressing tumor growth and prolonging survival time by inhibiting tumor cell proliferation and angiogenesis and increasing apoptosis of tumor cells. Overall, our data suggested that DOC-M/OXA-H may be potentially useful in the treatment of CRPC.

Whole-genome sequencing identifies new genetic alterations in meningiomas

The major known genetic contributor to meningioma formation was NF2, which is disrupted by mutation or loss in about 50% of tumors. Besides NF2, several recurrent driver mutations were recently uncovered through next-generation sequencing. Here, we performed whole-genome sequencing across 7 tumor-normal pairs to identify somatic genetic alterations in meningioma. As a result, Chromatin regulators, including multiple histone members, histone-modifying enzymes and several epigenetic regulators, are the major category among all of the identified copy number variants and single nucleotide variants. Notably, all samples contained copy number variants in histone members. Recurrent chromosomal rearrangements were detected on chromosome 22q, 6p21-p22 and 1q21, and most of the histone copy number variants occurred in these regions. These results will help to define the genetic landscape of meningioma and facilitate more effective genomics-guided personalized therapy.

Curcumin exerts its tumor suppressive function via inhibition of NEDD4 oncoprotein in glioma cancer cells

Glioblastoma is the most common brain cancer in adults. It represents one of the top ten malignant tumors with an average survival time of nine months despite treatments with surgery, radiotherapy and chemotherapy. Curcumin is a phytochemical turmeric isolated from root of the Curcuma longa plant. Accumulating evidence have proved that curcumin targets numerous cancer signaling pathways. The E3 ubiquitin ligase NEDD4, neural precursor cell expressed developmentally downregulated protein 4, is frequently overexpressed in various cancers. However, whether curcumin regulates NEDD4 expression has not been described in human cancers. Therefore, in this study, we explored the roles of NEDD4 in glioma cell proliferation, apoptosis and mobility. We further investigated whether curcumin exerts its antitumor activities via suppressing NEDD4 expression. We found that curcumin reduced the expression of NEDD4 and Notch1 and pAKT, leading to glioma cell growth inhibition, apoptosis, and suppression of migration and invasion. Moreover, deletion of NEDD4 expression enhanced the sensitivity of glioma cells to curcumin treatment. Thus, inactivation of NEDD4 by curcumin could be a promising approach for therapeutic intervention.