3D and 4D printed meta-biomaterials for bone tissue engineering

Abstract

A complex interplay of material, mechanical, and biological factors governs the performance of bone implants and scaffolds. Key determinants include surface functionalization, Young’s modulus of the base material (e.g., metals, or polymers), morphometric properties (e.g., curvature, porosity), mechanical features (e.g., effective elastic modulus, and Poisson’s ratio, defined as the negative ratio of transverse strain to longitudinal strain), and mass transport parameters (e.g., permeability). All these properties are often designed to enhance osseointegration significantly within the context of both bone replacement and regeneration. Regarding Poisson’s ratio, auxeticity (i.e., negative values of Poisson’s ratio) is a distinct property of trabecular bone, which assumes a high relevance for implant design.
To address these challenges, meta-biomaterials offer a unique opportunity to tune all the above-mentioned properties, enhancing the rate of tissue regeneration. These designer materials derive their effective properties mainly from their engineered microarchitecture rather than solely from their material composition. This has led to the development of meta-implants, a new generation of bone implants that exhibit rare or unprecedented functionalities. Conventional solid hip joint implants are mainly under mechanical bending, and due to their design, a physical gap may be created between the surrounding bone and the implant in such conventional implants. Under such circumstances, the particles released from the bearing surfaces may enter the gap and trigger an inflammatory response, replacing the bone tissue with fibrous tissue around the implant, a process known as osteolysis. On the other hand, meta-implants minimize the risk of such physical gaps between the surrounding bone and implants, thereby reducing the risk of implant loosening.
While the next generation of “hip meta-implants” addresses this issue by using auxeticity to minimize the risk of gaps forming, a fundamental challenge remains: “How can the effects of auxeticity on cell and tissue response be studied in isolation from many intrinsically coupled properties of meta-biomaterials (e.g., elastic/shear moduli, porosity, pore size, permeability)?” This question forms the core of my dissertation, which focuses on decoupling Poisson’s ratio from interdependent scaffold properties to achieve tunable auxetic behavior while preserving structural and functional integrity. Beyond structural design, understanding how Poisson’s ratio influences bone cell mechanobiology is vital for ensuring meta-implants promote healthy tissue regeneration. This leads to a key sub-question: “How does Poisson’s ratio affect bone cell response in meta-biomaterials?” Exploring this extends the research into the biological implications of meta-biomaterials.
Addressing these challenges demands an interdisciplinary approach, including i. mechanical design to isolate Poisson’s ratio from all other scaffold properties, ii.additive manufacturing (AM) of meta-biomaterials and their mechanical characterizations, iii. bone cell culture of meta-biomaterials and their cellular assessments, and iv. creating shape-morphing meta-biomaterials via 4D bioprinting for prospective dynamic cell culture studies.