Strontium and bisphosphonate coated iron foam scaffolds for osteoporotic fracture defect healing.

The purpose of this work was to investigate new bone formation in macroporous iron foams coated with strontium (FeSr) or bisphosphonate (FeBiP) compared to plain iron foam (Fe) and empty defect in a critical size metaphyseal bone defect model in ovariectomized rats. 60 female rats were subjected to bilateral ovariectomy and multi-deficient diet for 3 months. A 4 mm wedge shaped metaphyseal osteotomy was created, fixed with a mini-plate and subsequently filled with Fe, FeSr, FeBiP or left empty. After 6 weeks, µCt analysis revealed a statistically significant increased bone formation at the implant interface in FeSr compared to FeBiP (p = 0.035) and Fe (p = 0.002), respectively. Increased mineralized tissue was also seen within the pores in FeSr (p = 0.023) compared to Fe. Histomorphometry revealed significantly increased bone formation at the implant interface in FeSr (p < 0.001) and FeBiP (p = 0.006) compared to plain Fe with increased osteoblast and decreased osteoclast activity in combination with increased BMP2 and decreased RANKL/OPG in immunohistochemistry. ToF-SIMS analysis showed overlapping Ca signals with Fe for both FeSr and FeBiP thereby indicating tissue in-growth into the scaffolds. In conclusion, iron foam with strontium or bisphosphonate coating are of further interest in metaphyseal fracture defects in osteopenic bone.

Multi-scale simulation of plant stem reinforcement by brachysclereids: A case study in apple fruit peduncles.

Sclereid formation in addition to or in gaps of fragmented fibre rings is common in dicotyledonous plant stems. Whether this sclereid formation is force-triggered remains open so far. In fruit peduncles of several Malus species as modified plant stems, for example, the persistent fibre ring is displaced to the centre by formation of cortex parenchyma during growth. Parenchyma cells subsequently differentiate into an additional layer of brachysclereids, previously interpreted as an adaptation to continuously rising fruit loads. The present study pursues a multi-scale numerical modelling approach, to verify the important effect for different cellular architectures in both sclerenchyma categories on the stiffness of these tissues and the entire peduncle. First, different material properties are simulated analogue to plant tissues on the basis of three cell types. A regular three-dimensional and a random Voronoi microstructure combined with various mechanical cell wall parameters are applied. Using homogenisation simulations based on HILL's principle, numerical calculations predict a lower effective homogenised tissue stiffness of isodiametric brachysclereids compared to those of fibres, confirming experimentally obtained data from Malus fruit peduncles. Furthermore, a curved peduncle model with a complex arrangement of different material layers is generated. Diverse material sets are tested under three representative loadings, using an adaptive diffuse domain approach (AMDiS). The model explains the function of sclereids as considerable contributors to the stiffness against bending and tensile deformations, as well as torsion, especially in consequence of superimposed load conditions in the case of a curved plant stem.

A NOMPC-dependent membrane-microtubule connector is a candidate for the gating spring in fly mechanoreceptors.

BACKGROUND: Mechanoreceptors contain compliant elements, termed "gating springs," that transfer macroscopic stimuli impinging on the cells into microscopic stimuli that open the mechanosensitive channels. Evidence for gating springs comes from mechanical experiments; they have not been identified molecularly or ultrastructurally. RESULTS: We show that the filamentous structures that connect the plasma membrane to the microtubules are compliant structural elements in the mechanoreceptive organelle of fly campaniform receptors. These filaments colocalize with the ankyrin-repeat domain of the transient receptor potential (TRP) channel NOMPC. In addition, they resemble the purified ankyrin-repeat domain in size and shape. Most importantly, these filaments are nearly absent in nompC mutants and can be rescued by the nompC gene. Finally, mechanical modeling suggests that the filaments provide most of the compliance in the distal tip of the cell, thought to be the site of mechanotransduction. CONCLUSIONS: Our results provide strong evidence that the ankyrin-repeat domains of NOMPC structurally contribute to the membrane-microtubule connecting filaments. These filaments, as the most compliant element in the distal tip, are therefore good candidates for the gating springs.

Chemotaxis of mesenchymal stem cells within 3D biomimetic scaffolds--a modeling approach.

Bone tissue engineering is a promising strategy to repair local defects by implanting biodegradable scaffolds which undergo remodeling and are replaced completely by autologous bone tissue. Here, we consider a Keller-Segel model to describe the chemotaxis of bone marrow-derived mesenchymal stem cells (BMSCs) into a mineralized collagen scaffold. Following recent experimental results in bone healing, demonstrating that a sub-population of BMSCs can be guided into 3D scaffolds by gradients of signaling molecules such as SDF-1α, we consider a population of BMSCs on the surface of the pore structure of the scaffold and the chemoattractant SDF-1α within the pores. The resulting model is a coupled bulk/surface model which we reformulate following a diffuse-interface approach in which the geometry is implicitly described using a phase-field function. We explain how to obtain such an implicit representation and present numerical results on µCT-data for real scaffolds, assuming a diffusion of SDF-1α being coupled to diffusion and chemotaxis of the cells towards SDF-1α. We observe a slowing-down of BMSC ingrowth after the scaffold becomes saturated with SDF-1α, suggesting that a slow release of SDF-1α avoiding an early saturation is required to enable a complete colonization of the scaffold. The validation of our results is possible via SDF-1α release from injectable carrier materials, and an adaptation of our model to similar coupled bulk/surface problems such as remodeling processes seems attractive.