M. Mateu et al. Mechanically Tunable Bone Scaffolds: In Vivo Hardening of 3D-Printed Calcium Phosphate/Polycaprolactone Inks. Advanced Functional Materials

M. Mateu-Sanz, P. Varela, L. del-Mazo-Barbara, I. Lodoso-Torrecilla, E. Jiménez-Piqué, J. Franch, M. Alaminos, M.P. Ginebra. Mechanically Tunable Bone Scaffolds: In Vivo Hardening of 3D-Printed Calcium Phosphate/Polycaprolactone Inks. Adv. Funct. Mater. 2025, e09357. OPEN ACCESS.

doi: doi.org/10.1002/adfm.202509357

Abstract

Calcium phosphate 3D printing has revolutionized customized bone grafting. However, its inherent fragility limits clinical applicability. In this work, this problem is overcome by designing a composite scaffold able to harden in vivo. An α-tricalcium phosphate/polycaprolactone scaffold is developed that is ductile and tough when freshly printed and undergoes a transformation to hydroxyapatite following implantation in the body, resulting in its hardening. The hardening reaction, that takes place under physiological conditions and its impact on the biological response and osteogenic capacity of the material are investigated, both in vitro and in vivo, by comparing the in vivo hardening scaffolds with 3D printed hydroxyapatite and hydroxyapatite/polycaprolactone counterparts. In vitro results confirm the bioactivity, osteogenicity, and immunomodulatory potential of the polycaprolactone-based scaffolds. MG-63 cells increase the expression of osteogenic markers, while a downregulation of proinflammatory cytokines is observed in RAW246.7 cells. In vivo evaluation in a rabbit model confirms progressive bone infiltration and maturation, while osteoclast-mediated scaffold degradation is observed, being gradually resorbed and replaced by newly formed bone. Overall, in vivo hardening α-tricalcium phosphate/polycaprolactone scaffolds achieve mechanical properties comparable to human trabecular bone while retaining the biocompatibility and osteogenic potential of biomimetic hydroxyapatite.