Hasturk, O., Ermis, M., Demirci, U., Hasirci, N., and Hasirci, V. (2018). Square prism micropillars improve osteogenicity of poly (methyl methacrylate) surfaces. Journal of Materials Science: Materials in Medicine, 29(5), 53. DOI: 10.1007/s10856-018-6059-z

Osteogenicity and osteointegration of materials is one of the key elements of the success of bone implants. Poly(methyl methacrylate) (PMMA) is the basic compound of bone cement and has been widely investigated for other orthopedic applications, but its poor osteointegration and the subsequent loosening of implant material limits its widespread use as bone implants. Micropillar features on substrate surfaces were recently reported to modulate cell behavior through alteration of cell morphology and promotion of osteogenesis. Utilization of this pillar-decorated topography may be an effective approach to enhance osteogenicity of polymeric surfaces. The aim of this study was to investigate the effect of cell morphology on the micropillar features on attachment, proliferation, and osteogenic activity of human osteoblast-like cells. A series of solvent cast PMMA films decorated with 8 µm high square prism micropillars with pillar width and interpillar distances of 4, 8 and 16 µm were prepared from photolithographic templates, and primary human osteoblast-like cells (hOB) isolated from bone fragments were cultured on them. Micropillars increased cell attachment and early proliferation rate compared to unpatterned surfaces, and triggered distinct morphological changes in cell body and nucleus. Surfaces with pillar dimensions and gap width of 4 µm presented the best osteogenic activity. Expression of osteogenic marker genes was upregulated by micropillars, and cells formed bone nodule-like aggregates rich in bone matrix proteins and calcium phosphate. These results indicated that micropillar features enhance osteogenic activity on PMMA films, possibly by triggering morphological changes that promote the osteogenic phenotype of the cells.

Komez, A., Buyuksungur, S., Hasirci, V., and Hasirci, N. (2018). Effect of chemical structure on properties of polyurethanes: Temperature responsiveness and biocompatibility. Journal of Bioactive and Compatible Polymers, 33(5), 479-497. DOI: 10.1177/0883911518783233

Polyurethanes are known as one of the most biocompatible and inherently blood-compatible materials and have a wide range of applications in the medical field due to their controllable structure and properties. Durability, elasticity, elastomeric structure, fatigue resistance, versatility, and easy acceptance by the biological media after the application makes these polymers preferable in medical area. In this study, polyurethane films were prepared using poly(propylene-ethylene glycol) and either toluene-2,4-diisocyanate or 4,4′-methylenediphenyl diisocyanate without adding any other ingredients such as solvent, catalyst, or chain extender to prevent negative effects of leachable molecules. Mechanical tests were performed at room temperature while swelling tests were conducted in water and phosphate-buffered saline at 4°C, 25°C, and 37°C. Temperature responsiveness was observed for the samples synthesized using toluene-2,4-diisocyanate and poly(propylene-ethylene glycol). These samples had more than 100% swelling at 4°C and about 4% swelling at 25°C and 37°C. Cytocompatibility tests were performed by culturing the samples and their extracts with mouse fibroblast cells (L929). Viability of human umbilical vein endothelial cells was studied to examine the compatibility of the films for blood contacting devices. Both toluene-2,4-diisocyanate and 4,4-methylenediphenyl diisocyanate–based polyurethane films showed no cytotoxic effect and good biocompatibility. Oxygen plasma treatment enhanced hydrophilicity of the films. After plasma treatment, human umbilical vein endothelial cell attachment on toluene-2,4-diisocyanate–based polyurethane films improved and 4,4-methylenediphenyl diisocyanate–based polyurethane films maintained their high cell affinity. Polyurethanes presenting temperature responsiveness, high biocompatibility, and high affinity for human umbilical vein endothelial cells were synthesized in medical purity and in a reaction media involving only diisocyanate and diol components without addition of any solvent, chain extender, or catalyst. Polyurethanes with these properties and as produced in this study are reported for the first time in the literature.

Sezlev Bilecen, D., Uludag, H., and Hasirci, V. (2019). Development of PEI-RANK siRNA complex loaded PLGA nanocapsules for the treatment of osteoporosis. Tissue Engineering Part A, 25(1-2), 34-43. DOI: 10.1089/ten.tea.2017.0476

Osteoporosis, which is characterized by low bone mineral density and susceptibility to fracture, is caused by increased osteoclastic activity. Receptor activator of nuclear factor kappa B ligand (RANKL)/RANK signaling plays an important role in osteoclast differentiation and activation. The current treatment strategies for osteoporosis do not directly address this underlying cause and generates undesired side effects. This led to emergence of controlled delivery systems to increase drug bioavailability and efficacy specifically at the bone tissue. With better understanding of molecular pathology of bone, the use of small interfering RNA (siRNA) to inhibit translation of abnormal gene expression in cells is becoming a promising approach. In this study, we report a siRNA delivery system consisting of PEI:RANK siRNA complex entrapped in nanosized poly(lactic acid-co-glycolic acid) (PLGA) capsules intended to be used in the treatment of osteoporosis. The nanosize will enable the nanoparticles to be administered by intravenous injection. The RANK siRNA was complexed with polyethylenimine (PEI) and loaded into biodegradable PLGA nanocapsules (NCs). The PEI:RANK siRNA loaded nanocapsules significantly reduced (47%) RANK mRNA levels. The differentiation of osteoclast precursors to mature osteoclasts was significantly suppressed (∼54%). The reduction in the osteoclastic activity of the differentiated osteoclasts (55%) was found to be statistically significant. The siRNA delivery system developed in the study is planned to be tested i.v. in mouse and has the potential to be used as a novel alternative approach for the systemic treatment of osteoporosis.


Last Updated:
31/03/2022 - 16:02