A dopable bioink for augmented tissue engineering in craniofacial reconstruction: innovative pipeline for drug design and selective delivery through functionalized polymeric nanoparticles

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. Craniectomy/craniotomy procedures often leave bone defects that require cranioplasty to protect the underlying dura mater and the brain from physical insults. 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. 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.