Intelligent Supramolecular Modification for Implants: Endogenous Regulation of Bone Defect Repair in Osteoporosis.

Addressing osteoporosis-related bone defects, a supramolecular strategy is innovated for modifying carbon fiber reinforced polyether ether ketone (CF/PEEK) composites. By covalently attaching intelligent macromolecules via in situ RAFT polymerization, leveraging the unique pathological microenvironment in patients with iron-overloaded osteoporosis, intelligent supramolecular modified implant surface possesses multiple endogenous modulation capabilities. After implantation, surface brush-like macromolecules initially resist macrophage adhesion, thereby reducing the level of immune inflammation. Over time, the molecular chains undergo conformational changes due to Fe (III) mediated supramolecular self-assembly, transforming into mechanistic signals. These signals are then specifically transmitted to pre-osteoblast cell through the binding capacity of the KRSR short peptide at the molecular terminus, induced their osteogenic differentiation via the YAP/ß-catenin signaling axis. Furthermore, osteoblasts secrete alkaline phosphatase (ALP), which significantly hydrolyzes phosphate ester bonds in surface macromolecular side groups, resulting in the release of alendronate (ALN). This process further improves the local osteoporotic microenvironment. This intelligent surface modification tailors bone repair to individual conditions, automatically realize multiple endogenous regulation once implanted, and truly realize spontaneous activation of a series of responses conducive to bone repair in vivo. It is evidenced by improved bone regeneration in iron-overloaded osteoporotic rabbits and supported by in vitro validations.

Construction of a layer-by-layer self-assembled rosemarinic acid delivery system on the surface of CFRPEEK implants for enhanced anti-inflammatory and osseointegration activities.

Carbon fiber-reinforced polyether ether ketone (CFRPEEK) implants have attracted widespread attention in the field of clinical bone defect repair. However, the surface bioinertness confines the application of CFRPEEK implants. Inspired by the study of rosmarinic acid (RA)-promoted osteogenic differentiation, a self-assembly surface modification method based on electrostatic interactions, involving deposition of sodium carboxymethyl cellulose/chitosan and rosmarinic acid layer by layer on the surface of poly-L-lysine modified hydroxy CFRPEEK (SCPP/CC5@RA), is proposed to introduce RA on the surface of CFRPEEK for bioactivation. After layer-by-layer self-assembly (LBL), the surface of SCPP/CC5@RA exhibits weak electrophoresis (11.43 eV), suitable hydrophilicity, and bioactivity. The results of in vitro studies indicate that the RA release behavior of SCPP/CC5@RA effectively regulates the immune-inflammatory response and promotes the differentiation of osteoblasts. The rapid release of RA (0.17 µg mL-1) in the initial stage can downregulate the secretion of inflammation-related cytokines and significantly reduce oxidative stress levels; the sustained release of RA (0.06 µg mL-1) in the late stage can upregulate the expression of osteogenesis-related genes and induce mineralization of osteoblasts. Moreover, the rabbit tibia defect model demonstrates that the LBL technique can enhance the osseointegration of CFRPEEK implants. Compared with the control group, the bone trabecular thickness of the SCPP/CC5@RA group increases by 1.36 times, and the maximum pushing force increases by 2.67 times. In summary, this study provides a promising LBL based RA delivery system for the development of a dual-functional CFRPEEK implant in the field of bone implant biomaterials.

Construction of Multifunctional Zinc Ion Sustained-Release Biocoating on the Surface of Carbon Fiber Reinforced Polyetheretherketone with Enhanced Anti-inflammatory Activity, Angiogenesis, and Osteogenesis.

Current treatments of carbon fiber-reinforced polyetheretherketone (CFRPEEK) as orthopedic implants remain unsatisfactory due to the bioinert surface. The multifunctionalization of CFRPEEK, which endows it with regulating the immune inflammatory response, promoting angiogenesis, and accelerating osseointegration, is critical to the intricate bone healing process. Herein, a multifunctional zinc ion sustained-release biocoating, consisting of a carboxylated graphene oxide, zinc ion, and chitosan layer, covalently grafts on the surface of amino CFRPEEK (CP/GC@Zn/CS) to coordinate with the osseointegration process. The release behavior of zinc ions theoretically conforms to the different demands in the three stages of osseointegration, including the burst release of zinc ions in the early stage (7.27 µM, immunomodulation), continuous release in the middle stage (11.02 µM, angiogenesis), and slow release in the late stage (13.82 µM, osseointegration). In vitro assessments indicate that the multifunctional zinc ion sustained-release biocoating can remarkably regulate the immune inflammatory response, decrease the oxidative stress level, and promote angiogenesis and osteogenic differentiation. The rabbit tibial bone defect model further confirms that, compared to the unmodified group, the bone trabecular thickness of the CP/GC@Zn/CS group increases 1.32-fold, and the maximum push-out force improves 2.05-fold. In this study, a multifunctional zinc ion sustained-release biocoating constructed on the surface of CFRPEEK that conforms to the requirements of different osseointegration stages can be an attractive strategy for the clinical application of inert implants.

Multifunctional 3D sponge-like macroporous cryogel-modified long carbon fiber reinforced polyetheretherketone implants with enhanced vascularization and osseointegration.

Long carbon fiber reinforced polyetheretherketone (LCFRPEEK), a newly developed high-performance composite material, is being investigated as a possible orthopedic implant. However, its inability of angiogenesis and osseointegration after implantation makes it difficult for use as a long-term osteogenic fixation implant, which limits its scope of clinical application. Therefore, we design and construct a multifunctional 3D sponge-like macroporous cryogel to modify sulfonated LCFRPEEK using a cryogelation method based on free radical photopolymerization. The cryogel is mainly composed of graphene oxide-hydroxyapatite (GO-HAP) nanocomposites and gelatin methacrylate/polyethylene glycol diacrylate (GelMA/PEGDA). The results reveal that the multifunctional LCFRPEEK implant shows excellent biocompatibility and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) due to the incorporation of HAP nanoparticles into GO-HAP nanocomposites. Systematic in vivo animal studies further confirm that the multifunctional surface improves the bone remodeling and osseointegration of the LCFRPEEK implant. Additionally, the characteristic 3D sponge-like macroporous structures of cryogels promote the ingrowth and migration of human umbilical vein endothelial cells (HUVECs) and GO in the GO-HAP also boosts HUVEC migration and tube formation showing that they are beneficial for vascularization during osteogenesis. Therefore, the developed 3D sponge-like macroporous GelMA/PEGDA/GO-HAP cryogel fabricated on sulfonated LCFRPEEK implants with enhanced angiogenesis and osseointegration capabilities has great potential for clinical use as an orthopedic implant material.

An injectable adhesive antibacterial hydrogel wound dressing for infected skin wounds.

It's an exigent need for the improvement of novel antibacterial wound dressings with the increasing threats of drug resistance caused by excessive use of the antibiotics. In this work, an injectable, adhesive, hemostatic, biocompatible and bactericidal hydrogel wound dressing was fabricated. An injectable hydrogel can fill the irregular wound due to the characteristic of reversible sol-gel transition, whereas conventional dressings don't possess this ability. Oxidized alginate (ADA) and catechol-modified gelatin (Gel-Cat) were selected as the polymer backbones and they can crosslink in situ through double dynamic bonds, which were Schiff base and catechol-Fe coordinate bond; polydopamine decorated silver nanoparticles (PDA@Ag NPs) were also introduced into the hydrogel network. The double dynamic bonds endowed the hydrogel with injectable ability, shorter gelation time and enhanced mechanical property. And the aldehyde and catechol groups on the chains of ADA and Gel-Cat gave the hydrogel excellent adhesiveness. In addition, the PDA@Ag NPs in this system play two roles: one is bactericidal agent which can release from the hydrogel to kill the bacteria; the other is photothermal agent to convert 808 nm near-infrared light into heat to realize sterilization. In vitro study, the hydrogel displayed bactericidal ability against S. aureus and E. coli whether in photothermal antimicrobial test or agar diffusion test. In vivo test also testified that the hydrogel had a prominent therapeutic effect on infected wound through reducing inflammatory response and accelerating angiogenesis. Thus, we anticipate that our double dynamic bonds crosslinked hydrogel with PDA@Ag NPs as the antimicrobial agent can be a novel therapeutic way for infected wounds.

A FBXO7/EYA2-SCFFBXW7 axis promotes AXL-mediated maintenance of mesenchymal and immune evasion phenotypes of cancer cells.

A mesenchymal tumor phenotype associates with immunotherapy resistance, although the mechanism is unclear. Here, we identified FBXO7 as a maintenance regulator of mesenchymal and immune evasion phenotypes of cancer cells. FBXO7 bound and stabilized SIX1 co-transcriptional regulator EYA2, stimulating mesenchymal gene expression and suppressing IFNα/ß, chemokines CXCL9/10, and antigen presentation machinery, driven by AXL extracellular ligand GAS6. Ubiquitin ligase SCFFBXW7 antagonized this pathway by promoting EYA2 degradation. Targeting EYA2 Tyr phosphatase activity decreased mesenchymal phenotypes and enhanced cancer cell immunogenicity, resulting in attenuated tumor growth and metastasis, increased infiltration of cytotoxic T and NK cells, and enhanced anti-PD-1 therapy response in mouse tumor models. FBXO7 expression correlated with mesenchymal and immune-suppressive signatures in patients with cancer. An FBXO7-immune gene signature predicted immunotherapy responses. Collectively, the FBXO7/EYA2-SCFFBXW7 axis maintains mesenchymal and immune evasion phenotypes of cancer cells, providing rationale to evaluate FBXO7/EYA2 inhibitors in combination with immune-based therapies to enhance onco-immunotherapy responses.

The surface modification of long carbon fiber reinforced polyether ether ketone with bioactive composite hydrogel for effective osteogenicity.

Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) is fabricated using a three-dimensional (3D) needle-punched method in our previous work, which is considered as a potential orthopedic implant due to its high mechanical strength and isotropic properties, as well as having an elastic modulus similar to human cortical bone. However, the LCFRPEEK has inferior integration with bone tissue, limiting its clinical application. Thus, a facile surface modification method, using gelatin methacrylate/polyacrylamide composite hydrogel coating (GelMA/PAAM) loading with dexamethasone (Dex) on our newly-developed LCFRPEEK composite via concentrated sulfuric acid sulfonating and ultraviolet (UV) irradiation grafting methods, has been developed to tackle the problem. The results demonstrate that the GelMA/PAAM/Dex coating modified sulfonated LCFRPEEK (SCP/GP/Dex) has a hydrophilicity surface, a long-term Dex release capability and forms more bone-like apatite nodules in SBF. The SCP/GP/Dex also displays enhanced cytocompatibility and osteogenic differentiation in terms of rat bone marrow mesenchymal stem cells (rBMSCs) responses in vitro assay. The in vivo rat cranial defect assay confirms that SCP/GP/Dex boosts bone regeneration/osseointegration, which significantly improves osteogenic fixation between the implant and bone tissue. Therefore, the newly-developed LCFRPEEK modified via GelMA/PAAM/Dex bioactive coating exhibits improved biocompatibility and osteogenic integration capability, which has the basis for an orthopedic implant for clinical application.

A bi-layered scaffold of a poly(lactic-co-glycolic acid) nanofiber mat and an alginate-gelatin hydrogel for wound healing.

A resveratrol-loaded bi-layered scaffold (RBS) that consists of a resveratrol-loaded poly(lactic-co-glycolic acid) (Res-PLGA) electrospinning nanofiber mat (upper layer) and an alginate di-aldehyde (ADA)-gelatin (GEL) crosslinking hydrogel (ADA-GEL) (lower layer) was fabricated as a wound dressing material. It was made through mimicking the epidermis and dermis of the skin. The RBS exhibited good hemostatic ability and proper swelling ability. Furthermore, HaCaT cells and human embryonic skin fibroblasts (ESFs) were also cultured in the nanofiber layer and hydrogel layer of RBS, and the results indicated that both HaCaT and ESFs could grow well in the materials. The in vivo experiment using a Sprague-Dawley (SD) rat skin wound as a model showed that the RBS could accelerate the wound healing rate compared with the Res-PLGA group and ADA4-GEL6 group. These results indicated that this resveratrol-loaded bi-layered scaffold can be a potential candidate in promoting wound healing.

FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells.

Repetitive elements (REs) compose ∼50% of the human genome and are normally transcriptionally silenced, although the mechanism has remained elusive. Through an RNAi screen, we identified FBXO44 as an essential repressor of REs in cancer cells. FBXO44 bound H3K9me3-modified nucleosomes at the replication fork and recruited SUV39H1, CRL4, and Mi-2/NuRD to transcriptionally silence REs post-DNA replication. FBXO44/SUV39H1 inhibition reactivated REs, leading to DNA replication stress and stimulation of MAVS/STING antiviral pathways and interferon (IFN) signaling in cancer cells to promote decreased tumorigenicity, increased immunogenicity, and enhanced immunotherapy response. FBXO44 expression inversely correlated with replication stress, antiviral pathways, IFN signaling, and cytotoxic T cell infiltration in human cancers, while a FBXO44-immune gene signature correlated with improved immunotherapy response in cancer patients. FBXO44/SUV39H1 were dispensable in normal cells. Collectively, FBXO44/SUV39H1 are crucial repressors of RE transcription, and their inhibition selectively induces DNA replication stress and viral mimicry in cancer cells.

Knockdown of Kif20a inhibits growth of tumors in soft tissue sarcoma in vitro and in vivo.

Kif20a (Kinesin Family Member 20A), plays a role in cell mitosis, cell migration and intracellular transport. Numerous studies have demonstrated that Kif20a is abnormally highly expressed in a variety of tumors and shows poor prognosis. Soft tissue sarcoma (STS) represents a group of malignant tumors with poor prognosis. The role of Kif20a in STSs has not been systematically studied. In the present study, bioinformatics analysis, in vitro and in vivo experiments were conducted to investigate the function of Kif20a in STSs. In bioinformatics analysis higher KIf20a expression indicated a poor prognosis. Functional enrichment analysis indicated that Kif20a may be related to cell cycle, p53 and other signaling pathways. In vitro experiments showed that after the down-regulation of Kif20a, cell proliferation, migration and invasion were decreased, while apoptosis was increased. In vivo experiments revealed that Kif20a affected the proliferation of tumors in tumor-bearing mice. In summary, our findings revealed that Kif20a performs an important role in STS, indicating that it is a potential prognostic biomarker and potentially representing a therapeutic target for the disease.

Integrative Clustering Reveals a Novel Subtype of Soft Tissue Sarcoma With Poor Prognosis.

BACKGROUND: Soft tissue sarcomas (STSs) are heterogeneous at the clinical and molecular level and need to be further sub-clustered for treatment and prognosis. MATERIALS AND METHODS: STSs were sub-clustered based on RNAseq and miRNAseq data extracted from The Cancer Genome Atlas (TCGA) through the combined process of similarity network fusion (SNF) and consensus clustering (CC). The expression and clinical characteristics of each sub-cluster were analyzed. The genes differentially expressed (lncRNAs, miRNAs, and mRNAs) between the poor prognosis and good prognosis clusters were used to construct a competing endogenous RNA (ceRNA) network. Functional enrichment analysis was conducted and a hub network was extracted from the constructed ceRNA network. RESULTS: A total of 247 STSs were classified into three optimal sub-clusters, and patients in cluster 2 (C2) had a significantly lower rate of survival. A ceRNA network with 91 nodes and 167 edges was constructed according to the hypothesis of ceRNA. Functional enrichment analysis revealed that the network was mainly associated with organism development functions. Moreover, LncRNA (KCNQ1OT1)-miRNA (has-miR-29c-3p)-mRNA (JARID2, CDK8, DNMT3A, TET1)-competing endogenous gene pairs were identified as hub networks of the ceRNA network, in which each component showed survival significance. CONCLUSION: Integrative clustering analysis revealed that the STSs could be clustered into three sub-clusters. The ceRNA network, especially the subnetwork LncRNA (KCNQ1OT1)-miRNA (has-miR-29c-3p)-mRNA (JARID2, CDK8, DNMT3A, TET1) was a promising therapeutic target for the STS sub-cluster associated with a poor prognosis.

Three-Dimensional Coating of SF/PLGA Coaxial Nanofiber Membranes on Surfaces of Calcium Phosphate Cement for Enhanced Bone Regeneration.

Calcium phosphate cements (CPCs) have been widely used for the study of bone regeneration because of their excellent physical and chemical properties, but poor biocompatibility and lack of osteoinductivity limit potential clinical applications. To overcome these limitations, and based on our previous research, CPC scaffolds were prepared with CPC as the principal material and polyethylene glycol (PEG) as a porogen to introduce interconnected macropores. Using a bespoke electrospinning auxiliary receiver, silk fibroin (SF)/poly(lactide-co-glycolide) (PLGA) coaxial nanofibers containing dexamethasone (DXM) and recombinant human bone morphogenetic protein-2 (rhBMP2) were fabricated which were coated on the surface of the CPC. By comparing the surface morphology by SEM, hydrophilicity, results of FTIR spectroscopy, and mechanical properties of the composite materials fabricated using different electrospinning times (20, 40, 60 min), the CPC surface constructed by electrospinning for 40 min was found to exhibit the most appropriate physical and chemical properties. Therefore, composite materials were built for further study by electrospinning for 40 min. The osteogenic capacity of the SF/PLGA/CPC, SF-DXM/PLGA/CPC, and SF-DXM/PLGA-rhBMP2/CPC scaffolds was evaluated by in vitro cell culture with rat bone marrow mesenchymal stem cells (BMSCs) and using a rat cranial defect repair model. ALP activity, calcium deposition levels, upregulation of osteogenic genes, and bone regeneration in skull defects in rats with SF-DXM/PLGA-rhBMP2/CPC implants were significantly higher than in rats implanted with the other scaffolds. These results suggest that drug-loaded coaxial nanofiber coatings prepared on a CPC surface can continuously and effectively release bioactive drugs and further stimulate osteogenesis. Therefore, the SF-DXM/PLGA-rhBMP2/CPC scaffolds prepared in this study demonstrated the most significant potential for the treatment of bone defects.

CKS1 Germ Line Exclusion Is Essential for the Transition from Meiosis to Early Embryonic Development.

Cell division cycle (Cdc) kinase subunit (CKS) proteins bind cyclin-dependent kinases (CDKs) and play important roles in cell division control and development, though their precise molecular functions are not fully understood. Mammals express two closely related paralogs called CKS1 and CKS2, but only CKS2 is expressed in the germ line, indicating that it is solely responsible for regulating CDK functions in meiosis. Using cks2-/- knockout mice, we show that CKS2 is a crucial regulator of maturation-promoting factor (MPF; CDK1-cyclin A/B) activity in meiosis. cks2-/- oocytes display reduced and delayed MPF activity during meiotic progression, leading to defects in germinal vesicle breakdown (GVBD), anaphase-promoting complex/cyclosome (APC/C) activation, and meiotic spindle assembly. cks2-/- germ cells express significantly reduced levels of the MPF components CDK1 and cyclins A1/B1. Additionally, injection of MPF plus CKS2, but not MPF alone, restored normal GVBD in cks2-/- oocytes, demonstrating that GVBD is driven by a CKS2-dependent function of MPF. Moreover, we generated cks2cks1/cks1 knock-in mice and found that CKS1 can compensate for CKS2 in meiosis in vivo, but homozygous embryos arrested development at the 2- to 5-cell stage. Collectively, our results show that CKS2 is a crucial regulator of MPF functions in meiosis and that its paralog, CKS1, must be excluded from the germ line for proper embryonic development.

Co-expression Network Analysis Identifies Four Hub Genes Associated With Prognosis in Soft Tissue Sarcoma.

Background: Soft tissue sarcomas (STS) are heterogeneous tumors derived from mesenchymal cells that differentiate into soft tissues. The prognosis of patients who present with an STS is influenced by the regulation of a complex gene network. Methods: Weighted gene co-expression network analysis (WGCNA) was performed to identify gene modules associated with STS (Samples = 156). Results: Among the 11 modules identified, the black and blue modules were highly correlated with STS. However, using preservation analysis, the black module demonstrated low preservation, therefore the blue module was chosen as the module of interest. Furthermore, a total of 20 network hub genes were identified in the blue module, 12 of which were also hub nodes in the protein-protein interaction network of the module genes. Following additional verification, 4 of 12 genes (RRM2, BUB1B, CENPF, and KIF20A) demonstrated poorer overall survival and disease-free survival rate in the test datasets. In addition, gene set enrichment analysis (GSEA) demonstrated that samples with a high level of blue module eigengene (ME) were enriched in cell cycle and metabolism associated signaling pathways. Conclusion: In summary, co-expression network analysis identified four hub genes associated with prognosis for STS, which may diminish the prognosis by influencing cell cycle and metabolism associated signaling pathways.

Interleukin-35 suppresses antitumor activity of circulating CD8+ T cells in osteosarcoma patients.

Purpose/Aim of the study: Interleukin (IL)-35 is a newly identified IL-12 cytokine family member and reveals immunosuppressive activity to CD8+ T cells in inflammation, infectious diseases, and cancers. However, little is known regarding IL-35 function in osteosarcoma. Thus, the aim of the current study was to investigate the regulatory function of IL-35 to CD8+ T cells in osteosarcoma. Materials and methods: Thirty-five osteosarcoma patients and 20 healthy individuals were enrolled. Serum CD4+CD25+CD127dim/- regulatory T cells (Tregs) and CD8+ T cells were purified. IL-35 concentration in serum and cultured supernatants was measured by enzyme-linked immunosorbent assay. Osteosarcoma cell line MG-63 cells and CD8+ T cells were stimulated with recombinant IL-35 in vitro, and modulatory function of IL-35 on these cells was assessed by investigation of cellular proliferation, cell cycle, apoptosis, and cytokine production. Results: Serum IL-35 and Treg-secreting IL-35 were significantly elevated in osteosarcoma patients. IL-35 stimulation did not affect proliferation, apoptosis, or cell cycle of MG-63 cells. Purified peripheral CD8+ T cells from osteosarcoma patients revealed dysfunctional property, which presented as decreased mRNA expressions for perforin, granzyme B, and granulysin, as well as reduced cytolytic (direct lysis of target MG-63 cells) and noncytolytic (interferon-γ and tumor necrosis factor-α production) function in coculture systems. Moreover, IL-35 stimulation further diminished cytolytic and noncytolytic activity of CD8+ T cells from osteosarcoma patients. Conclusions: The current data indicated that IL-35 contributed to CD8+ T-cell dysfunction and limited antitumor immune response in osteosarcoma.

Using co-axial electrospray deposition to eliminate burst release of simvastatin from microparticles and to enhance induced osteogenesis.

Microparticles (MPs) exhibit fast dissolution, characterized by a burst drug release pattern. In the present work, we prepared core-shell MPs of simvastatin (SIM) and zein with chitosan (CS) and nano-hydroxyapatite (nHA) as a drug carrier using the coaxial electrospray deposition method. The morphology, formation and in vitro osteogenic differentiation of these MPs were studied. The synthetic MPs have a diameter of about 1 µm and they are composed of non-toxic natural materials. They provide an effective way to enable long-term sustained-release activity, which is controlled by their double layer structures. The CS-nHA/zein-SIM MPs presented a low initial burst release (approximately 35-47%) within the first 24 h of application followed by the sustained release for at least 4 weeks. In vitro cell culture experiments were performed and the results revealed that the CS-nHA/zein-SIM core-shell MPs were beneficial to the adhesion, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The CS-nHA/zein-SIM MPs with a low SIM concentration were beneficial to cell proliferation and promotion of osteogenic differentiation.

Tibial plateau fractures (AO type B3) combined with tibial tubercle fracture: Case report and review of the literature.

RATIONALE: Tibial tuberosity fractures most often occur in the adolescents. Fracture of tibial tuberosity in adults is extremely rare with only 5 reported cases till date. Tibial plateau fractures combined with tibial tubercle fractures are not common. PATIENT CONCERNS: We report here a type B3 tibial plateau fracture (AO classification) with a concomitant fracture of tibial tuberosity. DIAGNOSES: Anteroposterior and lateral knee view radiographs revealed a complex comminuted fracture of the right tibial plateau (AO Type B3; Schatzker Type IV) with tibial tubercle fracture. Three-dimensional computed tomography (CT) showed that the tibial media plateau was split into 2 pieces in the sagittal plane, along with the isolated tibial tubercle. INTERVENTIONS: The open procedure was performed first and a standard posteromedial approach for medial and posteromedial tibial plateau fracture was used with double locking plate fixation. The tibial tuberosity was fixed with a cortical screw. OUTCOMES: The patient showed full range of motion in right knee after 8 weeks. The patient was allowed full weight bearing at 4 months. Eight months after operation, he was asymptomatic, showed a full range of motion and good strength. He had returned to work with no limitations. LESSONS: Fractures of the partial tibial plateau combined with tibial tubercle are present and should not be ignored. Accurate diagnosis and proper treatment will help achieve favorable outcomes in these patients.

Paclitaxel and etoposide-loaded Poly (lactic-co-glycolic acid) microspheres fabricated by coaxial electrospraying for dual drug delivery.

In this study, we fabricated paclitaxel (PTX) and etoposide (ETP) loaded Poly (lactic-co-glycolic acid) (PLGA) microspheres with core-shell structures and particle sizes ranging from 1 to 4 µm by coaxial electrospraying. The microspheres were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM). The drug loading rate and entrapment efficiency of the microspheres were detected by high performance liquid chromatograph (HPLC). Moreover, the drug release profiles and degradation of drug-loaded PLGA microspheres in vitro were investigated, respectively. The distinct layered structure that existed in the manufactured core-shell microspheres can be observed by TEM. The in vitro release profiles indicated that the PLGA/PTX + ETP (PLGA/PE) microspheres exhibited the controlled release of two drugs in a sequential manner. Cell Counting Kit-8 was used to detect the toxic and side effects of the microspheres on bone tumor cells. PTX and ETP for combination drug therapy loaded microspheres had more cytotoxic effect on saos-2 osteosarcoma cells than the individual drugs. In conclusion, core-shell PLGA microspheres by electrospraying for combination drug therapy is promising for medicine applications, the PLGA/PE microspheres have some potential for osteosarcoma treatment.

Potential of rhBMP-2 and dexamethasone-loaded Zein/PLLA scaffolds for enhanced in vitro osteogenesis of mesenchymal stem cells.

Nanofibers fabricated by electrospinning simulate the extracellular matrix of bone cells and so researchers have taken a keen interest in them for regenerating bone tissue. The aim of this study was to fabricate ideal Zein/PLLA nanofibers by coaxial electrospinning and to load them with bone morphogenetic protein 2 (BMP-2) and dexamethasone (DEX) for dual controlled-release for bone tissue engineering applications. Morphology, surface hydrophilicity and core-shell construction were analyzed by environmental scanning electron microscopy (SEM), water contact angle and transmission electron microscopy (TEM). The properties of the scaffolds were studied in terms of the viability, morphology and osteogenic differentiation of mesenchymal stem cells (MSCs) that had been cultured on nanofiber mats of the Zein/PLLA and were determined using SEM, CCK-8 assay, quantitative ALP staining analysis, quantitative mineral deposition using Alizarin red staining (ARS), immunofluorescence staining and western blot analysis of osteogenic proteins. In vitro studies demonstrated that the biological activity of DEX and BMP-2 was retained in the dual-drug-loaded nanofiber scaffolds. A large quantity of DEX was released in the first three days, while the release of BMP-2 lasted for more than 21 days. In vitro osteogenesis studies showed that the drug-loaded nanofiber scaffolds induced osteogenic differentiation. Furthermore, the dual controlled-release of BMP-2 and DEX enhanced the osteogenic differentiation of MSCs resulting from synergistic effects. Therefore, Zein/PLLA nanofiber scaffolds loaded with BMP-2 and DEX have great potential in bone tissue engineering applications.