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Tissue Engineering

Tissue Engineering - Poster Session E

Poster BB1 - Design & Computational Modeling to Streamline Scaffold Design for Craniofacial Tissue Engineering

Saturday, October 26, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Craniofacial defects from birth or through traumatic injury require surgical treatment to restore functionality and cosmetic appearance. The gold standard includes implanting a bone graft, typically from the iliac cleft. Despite commonality, bone grafts lack specificity, increase infection risk, and greatly burden the healthcare system. Alternatively, tissue engineering can overcome the limitations of traditional bone grafts. Cryogel scaffolds are macroporous structures formed through freezing and thawing polymer solutions, resulting in a sponge-like construct with ideal pore sizes for cell infiltration and angiogenesis in bone applications; however, mechanical strength is reduced. To combat this, recent work by our group has demonstrated the benefits of incorporating three-dimensional (3D) frameworks (here, metastructures). Metastructures are 3D open-celled structures composed of repeating unit cells, resulting in highly tunable structures with negative Poisson’s ratio and high energy absorption. Using 3D printing (3DP) technologies, metastructural lattices can be fabricated from any printable material, including natural minerals found within bone extracellular matrix (ECM), such as hydroxyapatite (HAP). However, 3DP HAP is costly, and in cases where reiterative design is needed for TE applications, it results in unnecessary material waste. Instead, finite element analysis (FEA) may validate lattice structures before fabrication, accelerating the design process through in vitro HAP modeling. We hypothesize that bridging tissue engineering and metastructural design through FEA simulations will create a database from which the most mechanically resilient lattice structure can be identified for scaffold fabrication and bone applications.

Materials and

Methods:  This project addresses FEA simulation accuracy of metastrucural lattices and the potential prediction of in vitro mechanical behavior for craniofacial reconstruction. In identifying three geometries, with a focus on varying pore size (2mm, 2.5mm, 3mm), strut diameter (0.5mm, 0.25mm, 0.125mm), and strut angle (60°, 70°, 80°), this project will provide FEA simulations of ceramic HAP compared to in vitro mechanical testing with 3DP Grey v4 Resin in a proof-of-concept analysis. This will determine which parameter combination yields the most compelling lattice design for bone applications. Simulations were initially performed in SOLIDWORKS on five different lattices: cubic, tetrarchical, auxetic, honeycomb, and auxetic-honeycomb hybrids (Fig. 1), each in their “pilot” format (i.e., 2mm unit cell, 60° pore angle, and 0.5mm strut diameter), to determine which three designs would be 3DP based on their max yield strength. The three best-performing lattices were printed as cylinders in (diameter of 9mm and height of 10mm) and infiltrated by chitosan/gelatin cryogels. Briefly, the solution was crosslinked with glutaraldehyde and poured into the 3DP lattices within 3ml syringes. Subsequent freezing for 24 hrs, thawing, and lyophilization resulted in the combined structure (Fig. 2). Cryogel pore validation was completed via SEM imaging/python analysis and samples were hydrated and subjected to 70% uniaxial compressive strain (3mm) using the Instron 4469 machine (N=3/group). The strongest lattice that retained cryogel porosity was identified as the Hybrid Lattice. This scaffold was 3DP with HAP, filled with cryogel, and mechanically tested.

Results, Conclusions, and Discussions: Initial FEA testing focused on narrowing down five potential lattice designs from literature: cubic, tetrachiral, auxetic, honeycomb, and auxetic-honeycomb hybrid unit cells. FEA simulations with HAP (Fig. 3) resulted in the honeycomb, auxetic honeycomb, and a hybrid configuration (alternating the two unit cells) producing the highest max Von Mises yield strength (35.6, 80.8, 162 GPa, respectively). These three lattice designs were then 3DP, with a subset infiltrated with cryogel, and evaluated based on geometry, unit cell size (pore size), pore angle, and strut diameter. Compression testing identified the following ideal properties of hybrid lattice (mean EM: 362 MPa) (Fig. 4A), 3 mm unit cell (mean EM: 379 MPa) (Fig. 4B), 80° pore angle (mean EM: 389 MPa) (Fig. 4C), and 0.5 mm diameter (mean EM: 617 MPa), with only strut diameter variations resulting in statistical significance (p < 0.05) (Fig. 4D). Notably, related to pore integration, auxetic lattices (and the auxetic pores within the hybrid lattices), 2mm unit cell, 60° pore angle, and 0.125 mm strut diameter displayed optimal combined scaffold potential, as determined by full cryogel infiltration within the metastructure. Based on these combined results, and considering the lattice design that resulted in sufficient strength and cryogel integration, the Hybrid Lattice (2.5mm unit cell, 70° pore angle, and a 0.25 mm strut diameter, was chosen as optimal for bone applications. Ongoing work is focused on printing the design with HAP (Osteolite) resin and characterization, with and without cryogel scaffold. In conclusion, this initial assessment has demonstrated a match between FEA predictions in HAP and experimental mechanical values for the pilot lattice configurations. Ongoing work has consolidated the accuracy of FEA simulations in the context of 3DP HAP-cryogel hybrids, with further analysis focused on confirming cell viability and mineralization within these novel mineral scaffolds for bone.

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