Biomechanical performance of polycaprolactone (PCL)-based scaffold with rhBMP-2 in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. Resulting spine deformities include progressive coronal curvature, hypokyphosis, or frank lordosis in the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral discs have been surgically cleared and the disc spaces filled with graft material. Problems with bone graft harvest site morbidity as well as limited bone availability have led to the search for bone graft substitutes. Recently, a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone (PCL) has been developed for bone regeneration at load bearing sites. Combined with recombinant human bone morphogenic protein–2 (rhBMP-2), this has been shown to be successful in acting as a bone graft substitute in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft. This in vivo sheep study intends to evaluate the suitability of a custom designed medical grade PCL scaffold in combination with rhBMP-2 as a bone graft substitute in the setting of mini–thoracotomy surgery as a platform for ongoing research to benefit patients with adolescent idiopathic scoliosis

Modeling the growth of multicellular cancer spheroids in a\ud bioengineered 3D microenvironment and their treatment with an\ud anti-cancer drug

A critical step in the dissemination of ovarian cancer cells is the formation of multicellular spheroids from cells shed from the primary tumor. The objectives of this study were to establish and validate bioengineered three-dimensional (3D) microenvironments for culturing ovarian cancer cells in vitro and simultaneously to develop computational models describing the growth of multicellular spheroids in these bioengineered matrices. Cancer cells derived from human epithelial ovarian carcinoma were embedded within biomimetic hydrogels of varying stiffness and cultured for up to 4 weeks. Immunohistochemistry was used to quantify the dependence of cell proliferation and apoptosis on matrix stiffness, long-term culture and treatment with the anti-cancer drug paclitaxel.\ud \ud Two computational models were developed. In the first model, each spheroid was treated as an incompressible porous medium, whereas in the second model the concept of morphoelasticity was used to incorporate details about internal stresses and strains. Each model was formulated as a free boundary problem. Functional forms for cell proliferation and apoptosis motivated by the experimental work were applied and the predictions of both models compared with the output from the experiments. Both models simulated how the growth of cancer spheroids was influenced by mechanical and biochemical stimuli including matrix stiffness, culture time and treatment with paclitaxel. Our mathematical models provide new perspectives on previous experimental results and have informed the design of new 3D studies of multicellular cancer spheroids

Growth of confined cancer spheroids: a combined experimental and mathematical modelling approach

We have integrated a bioengineered three-dimensional platform by generating multicellular cancer spheroids in a controlled microenvironment with a mathematical model to investigate\ud confined tumour growth and to model its impact on cellular processes

The effect of beta-tricalcium phosphate on mechanical and thermal performances of poly(lactic acid)

Orthophosphates are bioactive crystals with similar structure, in terms of elemental composition and crystal nature, to human bone. In this work, biocomposite materials were prepared with poly(lactic acid) (PLA) as matrix, and betatricalcium phosphate (b-TCP) as osteoconductive filler by extrusion-compounding followed by conventional injection molding. The b-TCP load content was varied in the 10 40 wt% range and the influence of the b-TCP load on mechanical performance of PLA/b-TCP composites was evaluated. Mechanical properties of composites were obtained by standardized tensile, flexural, impact, and hardness tests. Thermal analysis of composites was carried out by means of differential scanning calorimetry; degradation at high temperatures was studied by thermogravimetric analysis; and the effect of the b-TCP load on dynamical response of composites was studied by mechanical thermal analysis in torsion mode. The bestbalanced properties were obtained for PLA composites containing 30 wt% b-TCP with a remarkable increase in the Young s modulus. These materials offer interesting properties to be used as base materials for medical applications such as interference screws due to high stiffness and mechanical resistance.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by "Conselleria d'Educacio, Cultura i Esport" - Generalitat Valenciana ref: GV/2014/008.Ferri Azor, JM.; Gisbert, I.; García Sanoguera, D.; Reig Pérez, MJ.; Balart Gimeno, RA. (2016). The effect of beta-tricalcium phosphate on mechanical and thermal performances of poly(lactic acid). Journal of Composite Materials. 50(30):4189-4198. https://doi.org/10.1177/0021998316636205S41894198503

A Method for Prostate and Breast Cancer Cell Spheroid Cultures Using Gelatin Methacryloyl-Based Hydrogels.

Modern tissue engineering technologies have delivered tools to recreate a cell's naturally occurring niche in vitro and to investigate normal and pathological cell-cell and cell-niche interactions. Hydrogel biomaterials mimic crucial properties of native extracellular matrices, including mechanical support, cell adhesion sites and proteolytic degradability. As such, they are applied as 3D cell culture platforms to replicate tissue-like architectures observed in vivo, allowing physiologically relevant cell behaviors. Here we review bioengineered 3D approaches used for prostate and breast cancer. Furthermore, we describe the synthesis and use of gelatin methacryloyl-based hydrogels as in vitro 3D cancer model. This platform is used to engineer the microenvironments for prostate and breast cancer cells to study processes regulating spheroid formation, cell functions and responses to therapeutic compounds. Collectively, these bioengineered 3D approaches provide cell biologists with innovative pre-clinical tools that integrate the complexity of the disease seen in patients to advance our knowledge of cancer cell physiology and the contribution of a tumor's surrounding milieu

A humanised tissue-engineered bone model allows species-specific breast cancer-related bone metastasis in vivo.

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer-related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell-bone interactions. In this study, two established tissue-engineered bone constructs (TEBCs) were applied to a breast cancer-related metastasis model. A cylindrical medical-grade polycaprolactone-tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate-coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA-MB-231, SUM1315, and MDA-MB-231BO breast cancer cells were cultured in polyethylene glycol-based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer-related bone metastasis seen in patients.Queensland University of Technology, the Australian Research Council (ARC) and the German Academic Exchange Service (DAAD

Automation of Pivot Sprinkler Irrigation Systems to More Efficiently Utilize Rainfall and Irrigation Water

A study was conducted to develop automated pivot sprinkler irrigation systems and determine if such systems use less water and energy than manually operated systems. The study was conducted near Earth, Texas, using irrigation systems located on producers farms. Sensors with transmitters and receivers were constructed and tested so that the irrigation systems can be controlled by wind, soil water tension, and rainfall. The sensors can be used separately or in combination to control the irrigation systems. For several reasons it was not possible to determine if automated systems use less water and energy than manually operated systems. The major reason was the low capacity of the wells (114 to 204 m3/hr) supplying the irrigation systems. To meet crop water requirements and losses due to evaporation and runoff, the well capacity should be at least 284 m3/hr. Since the wells could not supply adequate water, soil water tension was out of the tensiometer range for the last 60 days of the growing season. Considerable variation in soil water tension and content was noted between irrigation systems and within quadrants of each irrigation system. Systems planted to cotton would probably be easier to automate than those planted in corn because of the lower water requirements of cotton. The wind and rainfall controls have more promise to aid in increasing water use efficiency than controls activated by soil water sensors. Wind controls could be used during preirrigation when more time is available to apply water and rainfall controls could be an aid to producers with remotely located irrigation systems

Mechanical response of 3D Insert® PCL to compression

3D polymeric scaffolds are increasingly used for in vitro experiments aiming to mimic the environment found in vivo, to support for cellular growth and to induce differentiation through the application of external mechanical cues. In research, experimental results must be shown to be reproducible to be claimed as valid and the first clause to ensure consistency is to provide identical initial experimental conditions between trials. As a matter of fact, 3D structures fabricated in batch are supposed to present a highly reproducible geometry and consequently, to give the same bulk response to mechanical forces. This study aims to measure the overall mechanical response to compression of commercially available 3D Insert PCL scaffolds (3D PCL) fabricated in series by fuse deposition and evaluate how small changes in the architecture of scaffolds affect the mechanical response. The apparent elastic modulus (Ea) was evaluated by performing quasi-static mechanical tests at various temperatures showing a decrease in material stiffness from 5 MPa at 25 °C to 2.2 MPa at 37 °C. Then, a variability analysis revealed variations in Ea related to the repositioning of the sample into the testing machine, but also consistent differences comparing different scaffolds. To clarify the source of the differences measured in the mechanical response, the same scaffolds previously undergoing compression, were scanned by micro computed tomography (μCT) to identify any architectural difference. Eventually, to clarify the contribution given by differences in the architecture to the standard deviation of Ea, their mechanical response was qualitatively compared to a compact reference material such as polydimethylsiloxane (PDMS). This study links the geometry, architecture and mechanical response to compression of 3D PCL scaffolds and shows the importance of controlling such parameters in the manufacturing process to obtain scaffolds that can be used in vitro or in vivo under reproducible conditions