Substrate curvature as a cue to guide spatiotemporal cell and tissue organization

Callens, Sebastien J.P.; Uyttendaele, Rafael J.C.; Fratila‐Apachitei, Lidy E.; Zadpoor, Amir A.

doi:10.1016/j.biomaterials.2019.119739

Cited by 213 publications

(176 citation statements)

References 191 publications

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“…The elucidation of the mechanistic and cell-level diffusive and proliferative mechanisms required to match our experimental data is an important outcome of our study. It allows the prediction of the evolution of MC3T3cell-produced tissue in scaffold pores of new geometries, and can thus help design optimal scaffold pore shapes to meet conflicting constraints in both space and time, such as the requirement to bridge pores quickly while maintaining some degree of permeability [16].…”

Section: Resultsmentioning

confidence: 99%

“…There are many design questions that need to be addressed in the production of these scaffolds, such as determining their optimal size, shape and material properties [2][3][4]. These properties have been shown to impact cell attachment, viability, proliferation, migration, and differentiation, among other functions [10][11][12][13][14][15][16], and they could be tuned to control the manufacture of complex multicellular tissues or organs. Recent additive manufacturing techniques have leveraged these biophysical relationships in an ad hoc manner: by 3D printing bilayer cylindrical scaffolds as vascular grafts with endothelial and muscle cells [17] or by patterning scaffold pores or fibres * Corresponding author: pascal.buenzli@qut.edu.au to spatially control cell morphology and differentiation [18].…”

Section: Introductionmentioning

confidence: 99%

“…Several mathematical modelling strategies have been developed to explore the interplay between tissue growth and curvature effects [16], such as models based on the idea of mean curvature flow, that borrow ideas from fluid mechanics and the role of surface tension, but that do not consider cells explicitly [11][12][13][14][15]. Other modelling approaches consider the effects of cell-level behaviour and tissue crowding and spreading during surface growth, which lead to hyperbolic curvature flow models [24,22,25].…”

Section: Introductionmentioning

confidence: 99%

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Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Buenzli

Lanaro

Wong

et al. 2020

Preprint

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Tissue growth in bioscaffolds can be influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in a 3D printed scaffold by analysing experiments with a mathematical model. Experimentally, the new tissue infills the pore continually from the pore perimeter under strong curvature control, which leads to rounding off of the initial pore shape. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge the pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction-diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue; new cellular tissue in the model grows at a rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis therefore suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic cell proliferation and cell diffusion processes. The rates of these processes are unaffected by pore geometry, and can be predicted by simple reaction-diffusion models of cells that have robust, consistent behaviours.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Buenzli

Lanaro

Wong

et al. 2020

Preprint

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“…Recent studies have clearly shown that the geometry of porous biomaterials that are used for bone tissue engineering and/or bone substitution plays an important role in terms of the cell response, the rate of bone regeneration, and consequently the fate of the biomaterials [41]. Therefore, it is important to also investigate the effects of curvature on the rate of tissue generation by comparing concave, convex, and planar surfaces.…”

Section: Discussionmentioning

confidence: 99%

Bone Regeneration in Critical-Sized Bone Defects Treated with Additively Manufactured Porous Metallic Biomaterials: The Effects of Inelastic Mechanical Properties

et al. 2020

Self Cite

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Additively manufactured (AM) porous metallic biomaterials, in general, and AM porous titanium, in particular, have recently emerged as promising candidates for bone substitution. The porous design of such materials allows for mimicking the elastic mechanical properties of native bone tissue and showed to be effective in improving bone regeneration. It is, however, not clear what role the other mechanical properties of the bulk material such as ductility play in the performance of such biomaterials. In this study, we compared the bone tissue regeneration performance of AM porous biomaterials made from the commonly used titanium alloy Ti6Al4V-ELI with that of commercially pure titanium (CP-Ti). CP-Ti was selected because of its high ductility as compared to Ti6Al4V-ELI. Critical-sized (6 mm diameter) femoral defects in rats were treated with implants made from both Ti6Al4V-ELI and CP-Ti. Bone regeneration was assessed up to 11 weeks using micro-CT scanning. The regenerated bone volume was assessed ex vivo followed by histology and biomechanical testing to assess osseointegration of the implants. The bony defects treated with AM CP-Ti implants generally showed higher volumes of regenerated bone as compared to those treated with AM Ti6Al4V-ELI. The torsional strength of the two titanium groups were similar however, and both considerably lower than those measured for intact bony tissue. These findings show the importance of material type and ductility of the bulk material in the ability for bone tissue regeneration of AM porous biomaterials.

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“…Protein micropatterns on 2D substrates have provided valuable insight into the downstream effects of cell shape on intracellular and intranuclear protein organization and dynamics, however such adhesive patterns do not naturally exist in vivo. In the body as well as in tissue engineering scaffolds, cell-scale geometrical cues are primarily represented by 3D curved surfaces such as cavities or cylindrical structures (e.g., in the form of scaffold struts, natural vessels, or large collagen bundles) [91]. Substrate curvatures with radii of curvature similar or bigger than cell size have been shown to remarkably affect the morphology of human Bone Marrow Stromal Cells (hBMSCs) [68].…”

Section: Substrate Curvature Modulates Cytoskeletal Forces Acting On mentioning

confidence: 99%

Cellular Geometry Sensing at Different Length Scales and its Implications for Scaffold Design

2020

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Geometrical cues provided by the intrinsic architecture of tissues and implanted biomaterials have a high relevance in controlling cellular behavior. Knowledge of how cells sense and subsequently respond to complex geometrical cues of various sizes and origins is needed to understand the role of the architecture of the extracellular environment as a cell-instructive parameter. This is of particular interest in the field of tissue engineering, where the success of scaffold-guided tissue regeneration largely depends on the formation of new tissue in a native-like organization in order to ensure proper tissue function. A well-considered internal scaffold design (i.e., the inner architecture of the porous structure) can largely contribute to the desired cell and tissue organization. Advances in scaffold production techniques for tissue engineering purposes in the last years have provided the possibility to accurately create scaffolds with defined macroscale external and microscale internal architectures. Using the knowledge of how cells sense geometrical cues of different size ranges can drive the rational design of scaffolds that control cellular and tissue architecture. This concise review addresses the recently gained knowledge of the sensory mechanisms of cells towards geometrical cues of different sizes (from the nanometer to millimeter scale) and points out how this insight can contribute to informed architectural scaffold designs.

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Substrate curvature as a cue to guide spatiotemporal cell and tissue organization

Cited by 213 publications

References 191 publications

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Cell proliferation and migration explain pore bridging dynamics in 3D printed scaffolds of different pore size

Bone Regeneration in Critical-Sized Bone Defects Treated with Additively Manufactured Porous Metallic Biomaterials: The Effects of Inelastic Mechanical Properties

Cellular Geometry Sensing at Different Length Scales and its Implications for Scaffold Design

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