Functionalized Bioink Delivering Biomolecules for the Treatment of Craniofacial Diseases

NCT06533150 | Active Not Recruiting

• 1 other identifier: 6830
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Craniofacial Defects, Subtle; Skull Defect; Craniosynostoses

Outcome Measures

Primary Outcomes (1)

• Development of bio-ink nanoparticles complex

  Development of at least 50 gelatin-methacrylamide (GelMA)-based hydrogels bio-ink complexed with Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) showing a sustained and prolonged NPs release from GelMA matrix for 15-20 days. The efficiency of the developed complex will be evaluated by submerging the GelMA-NPs loaded with fluorescent compound with a bio-mimetic cell growth medium and quantifying the NPs released in the surnatant in time course experiments. NP quantification will be performed using UV-Vis Spectroscopy, Fluorescence Spectroscopy or particle counting such as Nanoparticle Tracking Analysis (NTA). NPs integrity will be studied by transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS).

  12 months

Secondary Outcomes (2)

• Development of bio-ink nanoparticles complex delivering selected biomolecules

  18 months

• Validation of the complex bio-ink efficiency in bone regeneration

  22 months

Interventions

multiomic profiling OTHER

2 aliquots of patients-derived bone tissue specimens (collected as surgical waste from routinely surgeries) will be collected and exploited from proteins and metabolites isolation according to standardized protocol. Then, samples will be digested using Filter-aided sample preparation digestion protocol and analysed by Liquid Chromatography Tandem Mass Spectrometry. Peptides will be loaded on the PepMap 100 C18 trap cartridge, and subsequently separated on an EASY Spray C18 analytical column. The mass spectrometer, equipped with a nanoESI spray source, operates in positive ion polarity and MS/MS mode. Also metabolites will be assessed by LC-MS/MS and will be separated by HPLC. Obtained results will be analyzed by integrated pathway analysis (IPA) to achieve the multiomic profiling of each patient thus identifying druggable targets to be exploited in drug design. The selected biomolecules will be then tested in patient cells using the developed bioink-nanoparticle complex.

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Paediatric patients undergoing surgery for craniosynostosis and other inborn defects (e.g. trauma, brain tumors) as per standard of care. Adult patients affected by trauma and tumors undergoing craniectomy as per standard of care. Pediatic patient will be enrolled at Fondazione Policlinico Universitario A. Gemelli IRCCS and at Azienda Ospedaliera di Rilievo Nazionale (AORN) Santobono Pausilipon. Adult patient will be enrolled at Policlinico di Bari. Samples derived from180 patients will be analysed for this study, 60 patients per UO will be enrolled prospectively.

You may qualify if:

• Paediatric patients (0-3 years) undergoing surgery for craniosynostosis and other inborn defects/trauma/brain tumors
• Adult patients (18-50 years) undergoing craniofacial surgery for (mainly) trauma and tumours

You may not qualify if:

• Paediatric patients older than 3 years of age
• Adults older than 50 years of age
• Paediatric patients and adult patients with other cranial diseases
• Patients with cranial defects that do not require craniofacial surgery

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC neurochirurgia Infantile

Roma, 00168, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Patient-derived cells isolated from tissue samples as well as tissue samples will be collected in biobanking infrastructures until the end of the study.

MeSH Terms

Conditions

Craniosynostoses

Condition Hierarchy (Ancestors)

Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Luca Massimi

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 1, 2024
• Study Start: October 7, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 14, 2025

Record last verified: 2024-07

Locations

IT (1)