Scaffolds for tissue engineering are usually designed to support cell viability with large adhesion surfaces and high permeability to nutrients and oxygen. Recent experiments support the idea that, in addition to surface roughness, elasticity and chemistry, the macroscopic geometry of the substrate also contributes to control the kinetics of tissue deposition. In this study, a previously proposed model for the behavior of osteoblasts on curved surfaces is used to predict the growth of bone matrix tissue in pores of different shapes. These predictions are compared to in vitro experiments with MC3T3-E1 pre-osteoblast cells cultivated in two-millimeter thick hydroxyapatite plates containing prismatic pores with square- or cross-shaped sections. The amount and shape of the tissue formed in the pores measured by phase contrast microscopy confirms the predictions of the model. In cross-shaped pores, the initial overall tissue deposition is twice as fast as in square-shaped pores. These results suggest that the optimization of pore shapes may improve the speed of ingrowth of bone tissue into porous scaffolds.
This study investigated how substrate geometry influences in-vitro tissue formation at length scales much larger than a single cell. Two-millimetre thick hydroxyapatite plates containing circular pores and semi-circular channels of 0.5 mm radius, mimicking osteons and hemi-osteons respectively, were incubated with MC3T3-E1 cells for 4 weeks. The amount and shape of the tissue formed in the pores, as measured using phase contrast microscopy, depended on the substrate geometry. It was further demonstrated, using a simple geometric model, that the observed curvature-controlled growth can be derived from the assembly of tensile elements on a curved substrate. These tensile elements are cells anchored on distant points of the curved surface, thus creating an actin “chord” by generating tension between the adhesion sites. Such a chord model was used to link the shape of the substrate to cell organisation and tissue patterning. In a pore with a circular cross-section, tissue growth increases the average curvature of the surface, whereas a semi-circular channel tends to be flattened out. Thereby, a single mechanism could describe new tissue growth in both cortical and trabecular bone after resorption due to remodelling. These similarities between in-vitro and in-vivo patterns suggest geometry as an important signal for bone remodelling.
Biological materials are often based on simple constituents and grown by the principle of self-assembly under ambient conditions. In particular, biomineralization approaches exploit efficient pathways of inorganic material synthesis. There is still a large gap between the complexity of natural systems and the practical utilization of bioinspired formation mechanisms. Here we describe a simple self-assembly route leading to a CaCO3 microlens array, somewhat reminiscent of the brittlestars' microlenses, with uniform size and focal length, by using a minimum number of components and equipment at ambient conditions. The formation mechanism of the amorphous CaCO3 microlens arrays was elucidated by confocal Raman spectroscopic imaging to be a two-step growth process mediated by the organic surfactant. CaCO3 microlens arrays are easy to fabricate, biocompatible and functional in amorphous or more stable crystalline forms. This shows that advanced optical materials can be generated by a simple mineral precipitation.
The collective self-organization of cells into three-dimensional structures can give rise to emergent physical properties such as fluid behavior. Here, we demonstrate that tissues growing on curved surfaces develop shapes with outer boundaries of constant mean curvature, similar to the energy minimizing forms of liquids wetting a surface. The amount of tissue formed depends on the shape of the substrate, with more tissue being deposited on highly concave surfaces, indicating a mechano-biological feedback mechanism. Inhibiting cell-contractility further revealed that active cellular forces are essential for generating sufficient surface stresses for the liquid-like behavior and growth of the tissue. This suggests that the mechanical signaling between cells and their physical environment, along with the continuous reorganization of cells and matrix is a key principle for the emergence of tissue shape.
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