Development of Tunable Hard and Soft Lattice Scaffolds for Multiscale Tissue Engineering Applications.

Abstract

The design of tunable hard and soft lattice scaffolds is key to advancing multiscale tissue engineering. In this study, we computationally designed and 3D-printed gyroid and diamond polylactic acid (PLA) scaffolds with varying lattice thicknesses and infills to modulate mechanical properties. Compression testing revealed a linear increase in modulus with increasing gyroid thickness (82-405 MPa), while diamond lattices with simple and body-centered infills reached up to 150 MPa, enabling tuning for both low- and high-density trabecular bone. Micro-CT analysis confirmed architectural fidelity, with scaffold porosity ranging from 63 to 85%, trabecular spacing (Tb.Sp) between 1.5 and 2.4 mm, and bone surface-to-volume ratios (BS/BV) of 3.2-6.4 mm²/mm³, suggesting tunability toward native trabecular bone. Surface modification with polydopamine (PDA) enhanced scaffold bioactivity, supporting robust human bone marrow-derived mesenchymal stem cell (hMSC) attachment, spreading, and stress fiber formation. Importantly, preliminary osteogenic evaluation revealed enhanced mineral deposition in PDA-coated scaffolds compared to uncoated PLA, with PDA-coated diamond architectures exhibiting the highest calcium deposition relative to both gyroid and uncoated diamond scaffolds. These results demonstrate that osteogenic potential can be tuned through both topology and surface modification. In parallel, soft scaffolds were developed by reinforcing alginate hydrogels with hydroxyapatite (HAP) nanocrystals and 3D bioprinting them into gyroid, hexagonal, and square honeycomb geometries. Rheological testing confirmed improved shear-thinning and print fidelity with increasing HAP content. Cell encapsulation studies with fibroblasts revealed scaffold-dependent differences, where Alamar Blue and PicoGreen assays demonstrated the highest metabolic activity and DNA content in the square honeycomb design, followed by hexagonal and gyroid lattices. Together, these findings establish a framework in which lattice geometry, material reinforcement, and surface biofunctionalization can be systematically combined to create tunable scaffolds for both load-bearing and soft tissue applications, laying the groundwork for hybrid systems with spatial and mechanical gradients to regenerate complex tissues.