Functionalized Bioink Delivering Biomolecules for the Treatment of Craniofacial Diseases

The study aims to address the challenges of craniofacial bone reconstruction in pediatric and adult patients affected by congenital craniofacial malformations (i.e. craniosynostosis), trauma or tumors, by developing an innovative biohybrid material with tunable rheological properties, serving as a sealing agent and defect filler. Craniectomy/craniotomy procedures often leave bone defects that require cranioplasty to protect the underlying dura mater and the brain from physical insults. Reconstruction of the viscerocranial skeleton poses additional challanges, due to the complex anatomy of the facial skull and significant esthetic and functional demands on its reconstruction. The study plans to develop a mouldable biosynthetic gelatin-methacrylamide (GelMA)-based hydrogel complexed with functionalized Poly (lactic-co-glycolic acid) (PLGA) nanoparticles for drug delivery. Osteoprogenitors cells (including mesenchymal stromal cells/osteoblasts and monocytes/osteoclasts) will be isolated from bone tissue fragments of enrolled patients and peripheral blood sample, respectively, to obtain 2D and 3D cultures mimicking the in vivo bone environment. High-throughput profiling of patients' samples will identify druggable targets for the bioactive compounds to be released by the bioink. In vitro validation will involve osteoprogenitor co-cultures derived from patients to assess uptake, release dynamics, biocompatibility, immunogenicity, and therapeutic effects of the developed complex. The final goal will be to develop a pre-prototype tissue engineering biocomposite for craniofacial bone reconstruction.