Validation of scaffold design optimization in bone tissue engineering: finite element modeling versus designed experiments

Abstract

This study reports the development of biological/synthetic scaffolds for bone tissue engineering (TE) via 3D bioplotting. These scaffolds were composed of poly(L-lactic-co-glycolic acid) (PLGA), type I collagen, and nano-hydroxyapatite (nHA) in an attempt to mimic the extracellular matrix of bone. The solvent used for processing the scaffolds was 1,1,1,3,3,3-hexafluoro-2-propanol. The produced scaffolds were characterized by scanning electron microscopy, microcomputed tomography, thermogravimetric analysis, and unconfined compression test. This study also sought to validate the use of finite-element optimization in COMSOL Multiphysics for scaffold design. Scaffold topology was simplified to three factors: nHA content, strand diameter, and strand spacing. These factors affect the ability of the scaffold to bear mechanical loads and how porous the structure can be. Twenty four scaffolds were constructed according to an I-optimal, split-plot designed experiment (DE) in order to generate experimental models of the factor-response relationships. Within the design region, the DE and COMSOL models agreed in their recommended optimal nHA (30%) and strand diameter (460 μm). However, the two methods disagreed by more than 30% in strand spacing (908 μm for DE; 601 μm for COMSOL). Seven scaffolds were 3D-bioplotted to validate the predictions of DE and COMSOL models (4.5-9.9 MPa measured moduli). The predictions for these scaffolds showed relative agreement for scaffold porosity (mean absolute percentage error of 4% for DE and 13% for COMSOL), but were substantially poorer for scaffold modulus (51% for DE; 21% for COMSOL), partly due to some simplifying assumptions made by the models. Expanding the design region in future experiments (e.g., higher nHA content and strand diameter), developing an efficient solvent evaporation method, and exerting a greater control over layer overlap could allow developing PLGA-nHA-collagen scaffolds to meet the mechanical requirements for bone TE.

Mechanobiological Approach to Design and Optimize Bone Tissue Scaffolds 3D Printed with Fused Deposition Modeling: A Feasibility Study

“…(ii) The typical distribution of the von Mises stresses within the scaffold model displays the presence of stress peaks in the proximity of the point where the generic strand enters in contact with the strand of the adjacent layer ( Figure 11). This same mechanical behavior was reported by Uth et al [34] who observed peaks of stress in alignment with the filaments of the previous layer.…”

“…Materials 2020, 13,648 17 of 21 the strand of the adjacent layer ( Figure 11). This same mechanical behavior was reported by Uth et al [34] who observed peaks of stress in alignment with the filaments of the previous layer. (iii) The amounts of bone predicted with the proposed algorithm are comparable with those predicted with other scaffolds based on different unit cell geometries [36,38,40,41].…”

“…Regarding the experimental measurements, only two dimensions-the strand diameter and the distance between the filaments-were measured and compared with the corresponding quantities obtained via the mechanobiology-based optimization algorithm. The choice of measuring only these two geometrical parameters is due to the fact that by adjusting the diameter and distance between extruded strands, it is possible to design various topologies with variable values of porosity and therefore to have a wide control of the scaffold micro-architecture [34]. All the other geometric parameters involved in the scaffold designing will certainly play a role less relevant than that played by the distance between the strands and the diameter of the filaments.…”

“…In one word, such studies that consider scaffold stiffness as the design variable aim to minimize the effects of stress shielding at the bone/scaffold interface [32,33]. Optimization strategies based on the compressive modulus expressed as a ratio between third principal stress and the prescribed compressive strain were also utilized to optimize the geometry of scaffolds fabricated with the FDM technique [34]. Singh et al have proposed a multifactor optimization for the development of biocompatible and biodegradable composite material-based feedstock filament of fused deposition modeling [35].…”

I‐Optimal design of poly(lactic‐co‐glycolic) acid/hydroxyapatite three‐dimensional scaffolds produced by thermally induced phase separation

“…Bone grafts and substitutes are used in millions of operations worldwide . Nevertheless, these therapies pose the risk of infection, immune response, disease transfer, or stress shielding . Tissue engineering is an alternative approach for the repair of damaged tissues and organs .…”