Multifunctional 3D-Printed Polylactic Acid/Hydroxyapatite Systems for Cranial Applications: Functionalization and Local Anti-Inflammatory Drug Delivery

Traumatic Brain Injuries (TBIs) frequently require cranioplasty procedures to restore skull integrity and protect underlying brain. Conventional cranial implants are often limited by inadequate osteointegration, risk of inflammation, infection, or the need for secondary surgical interventions. In this study, a multifunctional strategy for cranial reconstruction is proposed, combining additive manufacturing, bioactive surface functionalization, and local drug delivery. Porous polylactic acid (PLA) scaffolds were fabricated by Fused Deposition Modelling (FDM) to obtain lightweight structures with controlled porosity. The scaffolds were subsequently functionalized with hydroxyapatite coatings, deposited through sol–gel, to provide osteointegrative properties. To locally modulate post-implant inflammatory responses, a drug delivery system based on polycaprolactone (PCL) microparticles loaded with dexamethasone was developed and entrapped within hydroxyapatite-coated PLA structures. The produced systems were extensively characterized in terms of morphology, mechanical and thermal behavior, structural properties, biological response, and drug release behavior. Results demonstrated that the 3D-printed scaffolds exhibited homogeneous hydroxyapatite coatings, whose continuity and retention were enhanced by NaOH surface pre-treatment. Biological assays demonstrated that HAp coating significantly improved cell viability and osteogenic differentiation, confirming the osteoconductive potential of the scaffolds for craniofacial bone regeneration applications. Dexamethasone-loaded PCL microparticles were successfully integrated into the coated scaffolds, exhibiting controlled drug release, absence of cytotoxicity, and homogeneous distribution within the porous architecture, thereby demonstrating the feasibility of a multifunctional platform combining bone-regenerative and therapeutic delivery functionalities. Overall, the proposed multifunctional scaffolds represent a promising, low-cost and customizable approach for advanced cranioplasty applications, integrating structural support, osteointegration and local anti-inflammatory therapy within a single system.