Under a Creative Commons license
Abstract
The Poisson's ratio and elastic modulus are two parameters determining the elastic behavior of biomaterials.Moreover, there is an explicit analytical relationship describing the relationship between the design parameters of hexagonal unit cells and the Poisson's ratio (
of the resulting 2D meta-biomaterial [51]: (1) where and denote the transverse and longitudinal strains, respectively. For instance, in porous scaffolds or implants, the micro-architectural design determines the effective elastic
modulus with porosity and pore size serving as critical morphological parameters that need to be tailored
to mimic native tissues [12,13].In addition to the effective elastic modulus, the Poisson's ratio (i.e., the negative ratio of the transverse to
the longitudinal strain) is a crucial factor in biomaterial design and is known to play a significant role in
regulating cell behavior [9,[14], [15], [16], [17]].The outcomes of osteogenic differentiation (i.e., Runx2 immunofluorescent staining) and matrix mineralization (i.e., Alizarin red staining) assays indicated the significant potential impact of these meta-biomaterials in the field of bone tissue engineering, paving the way for the development of advanced bone meta-implants.The 2PP technique creates high-resolution, complex
meso-scale structures with micro-metric or sub-micrometric features [45], [46], [47], [48], [49], [50],
enabling the creation of 3D scaffolds with varying Poisson's ratios and allowing the study of the impact ofthese properties on the cell behavior in 3D.Subsequently, we measured the mechanical properties of IP-Q at the micro-scale (i.e., a cylinder with equal diameter and height of 30.0 um) for our FEM models using micro-compression, and similarly, characterized the mechanical properties of the meta-biomaterials at the meso-scale to validate our rational design approach.In this study, we first used computational mechanics and the finite element method (FEM) to rationally design meta-biomaterials with different values of the Poisson's ratio (range of - 0.74 to + 0.74) while maintaining similar values of the effective elastic modulus, porosity, pore size, and strut diameter.To tackle this, this study employed rational computational design to craft meta-biomaterials
with controlled Poisson's ratios, alongside consistent effective elastic modulus, porosity, and pore size.Graphical Abstract
Download : Download high-res image (382KB)
Download : Download full-size image
Keywords
Meta-biomaterials; Poisson's ratio; two-photon polymerization; preosteoblasts; metabolic activity;
differentiation
1.Introduction
Both the effective elastic modulus of the scaffolds (~stiffness) and the biomaterial's Young modulus may
modulate cell fate and subsequent tissue development through mechanotransduction pathways involving
cytoskeletal reorganization, and changes in gene expression and protein synthesis[1], [2], [3], [4].Advanced micro-additive manufacturing (micro-AM) techniques, such as two-photon polymerization (2PP),
have emerged as a valuable tool for exploring the influence of the Poisson's ratio on cell response in 3D
micro-/meso-scale structures [41], [42], [43], [44].Then, we employed the 2PP technique to fabricate these complex meta-biomaterials at the meso-scale (i.e., 1356.0x1356.0x1800.0 um3 with a strut diameter of 36.0 um) using a methacrylate photosensitive polymer (called IP-QTM).The porosity of such meta-biomaterials is defined as: (2) where and respectively refer to the volumes of the meta-biomaterial calculated from a CAD
software and the volume of a solid cube encompassing the entire meta-biomaterial structure ( in Figure 1.a.i).Interestingly, the meta-biomaterials exhibited different cell-induced deformations (e.g., shrinkage or local bending) as observed via scanning electron microscopy.Finally, we evaluated the response of mouse preosteoblasts seeded onto the meta-biomaterials by assessing their viability, metabolic activity, spatiotemporal organization, as well as the osteogenic differentiation and matrix mineralization.The complexity arises from intertwined micro-
architectural parameters, such as porosity and elastic modulus, making it challenging to isolate the
Poisson's ratio.Several strategies can be employed to modulate the effective elastic modulus of scaffolds depending on the
targeted tissue, biochemical properties, and manufacturing techniques.The micro-architecture of meta-biomaterials determines not only the Poisson's ratio but also several other parameters that also influence cell response, such as porosity, pore size, and effective elastic modulus.Here, we computationally design metabiomaterials with controlled Poisson's ratios, ranging between -0.74 and +0.74, while maintaining consistent porosity, pore size, and effective elastic modulus.The 3D meta-biomaterials were additively manufactured at the micro-scale using two-photon polymerization (2PP), and were mechanically evaluated at the meso-scale.It is,
therefore, necessary to consider the elastic modulus of the target tissue in the design of biomaterials and
scaffolds, which can vary greatly from soft tissues (e.g., brain with an elastic modulus of approximately 1-4 kPa
[5], [6], [7]) to hard tissues (e.g., cancellous bone with an elastic modulus of around 0.04-1 GPa [6,8]).This offers new opportunities for developing innovative 3D-engineered microenvironments that can be customized for specific tissue engineering and regenerative medicine applications.However, rational design
techniques could be used to decouple the Poisson's ratio of meta-biomaterials from their effective elastic
modulus and morphological properties.Statement of Significance What's this?Material and methods
2.1.2.