A dopable bioink augmented tissue engineering incraniofacial reconstruction: Innovative pipeline for drug design and selective delivery through functionalized polymer Nanonaprticles

This project aims to address the challenges of craniofacial bone reconstruction, particularly in pediatric patients, by developing an innovative biohybrid material with tunable rheological properties, serving as a sealing agent and defect filler. The most prevalent indications to craniofacial surgery include congenital malformations (i.e. craniosyostosis), trauma and tumors. 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. Overall this area places the highest demands on the surgeon. The study plans to create a bioink using a combination of collagen-based hydrogels and polymeric nanoparticles that can deliver bioactive molecules. Multiomic profiling of the bone defect environment will be used to identify druggable targets and guide drug design, leading to patient-tailored bone regeneration and reduced complications. Current biomaterials and procedures have limitations such as the limited supply of autologous bone and the inability of alloplastic materials to achieve functional bone regeneration, often undergoing dislocation due to poor osteointegration. Their inadequacy is particulary evident for pediatric patients who require skull elasticity to accommodate growth. This significantly impacts healthcare systems increasing the costs for hospitalization, causing severe complications and repeated surgeries. The properties of craniofacial implants depend on biomaterials and their biomimetic features. A personalized rheological and bio-inspired implant design could address these challenges. In this context, hydrogel-based bioinks endowed with bioactive molecule releases may be exploited stabilize bone implants, adapting to diverse and complex defect areas, impede implant site infections, and promote functional bone healing. The specific aims of the project include the assembly of a mouldable biosynthetic collagen-based polymer matrix with functionalized nanoparticles for drug delivery. This system will target osteogenic niche modulation and reduce infection risk. High-throughput profiling of patients' samples will identify targets for the bioactive compounds to be released by the bioink. In vitro validation will involve co-culture systems to assess uptake, release dynamics, biocompatibility, immunogenicity, and therapeutic effects. The final goal will be to develop a pre-prototype tissue engineering biocomposite for craniofacial bone reconstruction. This project's significance lies in the potential for major innovations in craniofacial bone reconstruction. The biohybrid material with tunable rheological properties and controlled drug delivery can improve outcomes in craniofacial procedures. The personalized approach, guided by multiomic profiling, offers tailored therapies and precise interventions. These advancements can enhance perioperative outcomes, reduce complications, and improve quality of life for pediatric patients and beyond. The collaboration between researchers with expertise in neurosurgery, genetics, cell and molecular biology, biochemistry, and drug design ensures a synergistic and comprehensive approach to the project.