Article Database

Characterization of porcine circulating progenitor cells: toward a functional endothelium

Abstract:

The lack of available healthy vessels, significant patient morbidity, and high costs hinders the successful clinical utilization of autologous endothelial cells (ECs). Herein we assess the feasibility of using endothelial progenitor cells (EPC) found in circulating blood to engineer a functional endothelium on poly(1,8-octanediol-co-citrate) (POC), a hemocompatible and biodegradable elastomer used in vascular tissue engineering. EPCs were isolated from porcine blood and biochemically differentiated into porcine endothelial (PE)-like cells in vitro. Once differentiated, EC phenotype and function on POC were assessed according to the presence of the EC-specific markers von Willebrand factor, platelet EC adhesion molecule, and vascular endothelial cadherin; metabolism of acetylated low-density lipoprotein; secretion of the anti-thrombogenic factors nitric oxide and prostacyclin; and inhibition of platelet adhesion and clotting processes in vitro. The effects of PE-like cells on porcine aortic smooth muscle cells (PASMCs) were also investigated via co-culture. PE-like cells on POC had phenotype, function, and clotting responses similar to those of primary aortic ECs. The presence of PE-like cells resulted in a 71 ± 20% decrease in PASMC proliferation; a 52 ± 2% decrease in the protein:deoxyribonucleic acid ratio; and an elongated, spindle-shaped morphology indicative of a shift from the proliferative to the contractile phenotype. These data suggest that EPCs and POC can provide the basis for a functional tissue-engineered endothelium.

Biodegradable magnesium alloys, methods of manufacture thereof and articles comprising the same

Abstract:

Disclosed herein is an article comprising a metal alloy; where the metal alloy comprises a base metal, a second element and a third element; where the base metal is magnesium, calcium, strontium, zinc, or a combination thereof; where the second element is chemically different from the third element; and where the second element and the third element are scandium, yttrium, gadolium, cerium, neodymium, dysporium, or a combination thereof; and a protective layer disposed upon the metal alloy and is reactively bonded to the metal alloy; where the protective layer comprises a base non-metallic derivative, a second non-metallic derivative and a third non-metallic derivative of metals present in the metal alloy; and where the base non-metallic derivative, the second non-metallic derivative and the third non-metallic derivative are all chemically different from one another.

Biodegradable magnesium alloys, methods of manufacture thereof and articles comprising the same

Abstract:

This application claims priority to International Application No. PCT/US14/045364 filed on Jul. 3, 2014, which claims the benefit of U.S. Provisional Patent Application No. 61/842,456 filed on Jul. 3, 2013, the entire contents of both are hereby incorporated by reference.

Biocompatible evaluation of barium titanate foamed ceramic structures for orthopedic applications

Abstract:

The potential of barium titanate (BT) to be electrically active makes it a material of interest in regenerative medicine. To enhance the understanding of this material for orthopedic applications, the in vitro biocompatibility of porous BT fabricated using a direct foaming technique was investigated. Characterization of the resultant foams yielded an overall porosity between 50 and 70% with average pore size in excess of 30 µm in diameter. A mouse osteoblast (7F2) cell line was cultured with the BT to determine the extent of the foams’ toxicity using a LDH assay. After 72 h, BT foams showed a comparable cytotoxicity of 6.4 ± 0.8% to the 8.4 ± 1.5% of porous 45S5 Bioglass®. The in vitro inflammatory response elicited from porous BT was measured as a function of tumor necrosis factor alpha (TNF‐α) secreted from a human monocytic leukemia cell line (THP‐1). Results indicate that the BT foams do not cause a significant inflammatory response, eliciting a 9.4 ± 1.3 pg of TNF‐α per mL of media compared with 20.2 ± 2.3 pg/mL from untreated cells. These results indicate that porous BT does not exhibit short term cytotoxicity and has potential for orthopedic tissue engineering applications.

Biocompatibility evaluation of porous ceria foams for orthopedic tissue engineering

Abstract:

Ceria ceramics have the unique ability to protect cells from free radical‐induced damage, making them materials of interest for biomedical applications. To expand upon the understanding of the potential of ceria as a biomaterial, porous ceria, fabricated via direct foaming, was investigated to assess its biocompatibility and its ability to scavenge free radicals. A mouse osteoblast (7F2) cell line was cultured with the ceria foams to determine the extent of the foams’ toxicity. Toxicity assessments indicate that mouse osteoblasts cultured directly on the ceria scaffold for 72 h did not show a significant (p > 0.05) increase in toxicity, but rather show comparable toxicity to cells cultured on porous 45S5 Bioglass®. The in vitro inflammatory response elicited from porous ceria foams was measured as a function of tumor necrosis factor alpha (TNF‐α) secreted from a human monocytic leukemia cell line. Results indicate that the ceria foams do not cause a significant inflammatory response, eliciting a response of 27.1 ± 7.1 pg mL⁻¹ of TNF‐α compared to 36.3 ± 5.8 pg mL⁻¹ from cells on Bioglass, and 20.1 ± 2.9 pg mL⁻¹ from untreated cells. Finally, we report cellular toxicity in response to free radicals from tert‐butyl hydroperoxide with and without foamed ceria. Our preliminary results show that the foamed ceria is able to decrease the toxic effect of induced oxidative stress. Collectively, this study demonstrates that foamed ceria scaffolds do not activate an inflammatory response, and show potential free radical scavenging ability, thus they have promise as an orthopedic biomaterial.

Anti‐VEGF‐R2 Aptamer and RGD Peptide Synergize in a Bifunctional Hydrogel for Enhanced Angiogenic Potential

Abstract:

Hydrogels have gained interest for use in tissue regeneration and wound healing because of their absorbing and swelling properties as well as their ability to mimic the natural extracellular matrix. Their use in wound healing specifically may be in the form of a patch or wound dressing or they may be administered within the wound bed as a filler, gel in situ, to promote healing. Thiolated hyaluronic acid‐polyethylene diacrylate (tHA‐PEGDA) hydrogels are ideal for this purpose due to their short gelation times at physiological temperature and pH. But these hydrogels alone are not enough and require added components to gain bioactivity. In this work, RGD adhesion peptides and an antivascular endothelial growth factor receptor‐2 (VEGF‐R2) DNA aptamer are incorporated into a tHA‐PEGDA hydrogel to make a bifunctional hyaluronic acid hydrogel. RGD peptides promote attachment and growth of cells while the anti‐VEGF‐R2 DNA aptamer seems to improve cell viability, induce cell migration, and spur the onset of angiogenesis by tube formation by endothelial cells. This bifunctional hydrogel supports cell culture and has improved biological properties. The data suggest that these hydrogels can be used for advanced tissue regeneration applications such as in wound healing.

Advanced Nanocomposites for Bone Regeneration

Abstract:

The field of orthopedic tissue engineering is quickly expanding with the development of novel materials and strategies designed for rapid bone regeneration. While autologous bone grafts continue to be the standard of care, drawbacks include donor-site morbidity and short tissue supplies. Herein we report a novel nanocomposite sponge composed of poly(1,8-octanediol-co-citrate) (POC) and the bioactive ceramic β-tricalcium phosphate (TCP). We show that these nanocomposite sponges can be used as a depot for bone-producing (a.k.a. osteogenic) growth factors. In vitro bioactivity is demonstrated by significant upregulation of osteogenic genes, osteopontin (∼3 fold increase), osteocalcin (∼22 fold increase), alkaline phosphatase (∼10 fold increase), and transcription factor, RUNX2 (∼5 fold increase) over basal expression levels in mesenchymal stem cells. In vivo osteogenicity and biocompatibility is demonstrated in a standard subcutaneous implant model in rat. Results show that the nanocomposite sponge supports complete cell infiltration, minimal adverse foreign body response, positive cellular proliferation, and cellular expression of osteogenic markers in subcutaneous tissue. The results shown herein are encouraging and support the use of this sponge for future bone tissue engineering efforts.

Analysis of an Ovarian Cancer Cohort in a Health System with a Safety-Net Hospital and a Comprehensive Cancer Center

Abstract:

Abstract not available at this time.

A study of a biodegradable Mg–3Sc–3Y alloy and the effect of self-passivation on the in vitro degradation

Abstract:

Abstract POSTER-BIOL-1312: The role of BRCA and CEBPD in serous ovarian cancer carcinogenesis

Abstract:

Introduction: The most common histotype representing 90% of ovarian cancer cases is High Grade Serous Carcinoma. In a previous publication we found C/EBP-δ to be significantly increased in fallopian tube epithelial in BRCA1 mutation carriers and specifically in the luteal phase of the menstrual cycle, by transcription and protein expression. C/EBP-δ represents a master regulator of gene transcription primarily through STAT3 activation in many tumor types. C/EBP-δ is commonly induced by stress and is associated with increased DNA damage. Additionally, studies in breast cancer showed that C/EBP-δ could interact with FANCD2, which is involved in DNA repair along with BRCA1 and BRCA2. C/EBP-δ plays a dichotomous role in tumor suppression and promotion, which is tissue specific. We therefore studied the 1) differential expression of C/EBP-δ in serous carcinoma 2) expression of C/EBP-δ in precursor lesions (STIC) and 3) modeled the effect of over-expression of C/EBP-δ in an in vitro fallopian tube cell culture model.

Methods: The study protocol for collection of tissue and clinical information for all patients was approved by the UHN REB. Tissue microarrays containing the different histotypes were used to validate immunohistochemical protein expression. Fallopian tubes with lesions classified as STIC using published diagnostic criteria, were selected (n=15) from women undergoing surgery for HGSC. FTE Cells were propagated on collagen IV coated plates in MCDB105/M199 media supplemented with BPE, EGF, insulin and hydrocortisone. Cells were immortalized via double infection with a lentiviral dominant negative TP53 vector and retroviruses with E7 and hTERT. Statistical analysis was performed using ANOVA (p<0.05) and Fisher’s Exact Test p<0.05).

Results/Conclusion: C/EBP-δ is down-regulated in over 60% of HGSC analyzed, an observation which is also histotype specific as LGSC tumors show high expression levels (p<0.01). 60% of C/EBP-δ protein expression exhibited a gradual decrease from the normal FTE to the p53-signatures and the STICs and lost in concomitant HGSC. This indicates an inverse correlation between C/EBP-δ and proliferative index. This suggests that C/EBP-δ regulates cell-cycle progression in the FTE possibly through the G2/M checkpoint and is a potential tumor suppressor in HGSC. In short-term cultures of FTE cell lines, over-expression of C/EBP-δ did not affect proliferation but may affect long-term growth. High expression of C/EBP-δ in FTE cells correlated with decreased vimentin, N-cadherin, ACTA2 and Zeb2 while and in Twist1 and mir21 expression. This data is consistent with the phenotypic effect observed by over-expressing C/EBP-δ in cell culture and indicates an involvement of C/EBP-δ in mesenchymal-to-epithelial transition during high-grade serous carcinogenesis.