Christos Leliopoulos: Quantitative Design and Additive Manufacturing of Resorbable Composite Biomaterial for Bone Regeneration

Abstract

Successful tissue regeneration depends on the synergy between appropriate materials and a suitable 3D architecture. Additive manufacturing stands out as the optimal process for creating this architecture because it drives the creation of implants specific to the defect of the patient and allows for control over the macro porosity of the implant. However, to facilitate this fabrication process, the material system requires a polymeric component that induces shear-thinning properties. An extracellular matrix-derived biopolymer such as hyaluronic acid is a high-potential candidate for tissue regeneration due to its biological relevance and ability to interact with sensitive growth factors as well as inorganic ions. When combined with calcium phosphate ceramics, specifically brushite and beta-tricalcium phosphate (β-TCP), anionic biopolymers form composite systems designed to mimic the composition of natural bone. However, to translate these components into functional scaffolds, the polymer backbone must undergo precise chemical modifications to obtain chemically crosslinked hydrogels. These modifications are responsible for driving properties that are crucial for fabrication, such as shear-thinning and self-healing, which enable the processing of the material into complex geometries. Consequently, the proper characterization of these modifications is of paramount importance, as they govern the network formation and stability of the final construct.

To address this challenge, specifically to control and quantify chemical modifications, a universal quantification strategy was established based on the stoichiometric analysis of counterions. This approach successfully bridges the analytical gap for “spectroscopically silent” and insoluble polymer networks, ensuring chemical consistency without reliance on label-based assays. Simultaneously, the characterization of self-healing material behaviors was critically reassessed to distinguish true functional repair from rheological artifacts, providing a robust metric to verify the recovery of mechanical competence. 

Applying these analytical and mechanical methodologies, a composite scaffold system was developed that decouples architectural fabrication from the inherent limitations of the material. The resulting constructs exhibited a profound enhancement in mechanical performance, characterized by a significant increase in compressive strength and stiffness while retaining essential ductility. Structurally, the evolution of the material yielded a highly interconnected internal pore network, optimizing the scaffold for biological permeability. In vivo evaluation confirmed the efficacy of this system, demonstrating robust bone regeneration and integration in a critical-size defect model.