Customized Bone Allografts by 3D-printing

NCT05700526 | Enrolling By Invitation

• 1 other identifier: CE-AVEC 301/2022/Sper/IOR
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Virtual surgical planning (VSP), the simulation of bone corrections in virtual reality ("Computer Aided Surgical Simulation": CASS) and 3D printing of customized implants and devices are achieving an increasingly central role in clinical practice and orthopaedic surgery. Those technologies and processes allow an allow incredibly versatile and accurate planning and reproduction of complex bone correction or joint replacement procedures. Recent and converging evidence document how the use of these technologies is able to significantly reduce surgical times, bleeding and intra-operative complications, and the use of intra-operative fluoroscopy. Due to the collaboration between the ward of Pediatric Orthopedics and Traumatology of the Rizzoli Orthopedic Institute and the Department of Industrial Engineering (DIN) of the University of Bologna it was possible to experiment, validate and introduce simulation, planning and personalization technologies of interventions of corrective surgery of Musculoskeletal Disorders (MSDs) of the limbs in childhood and developmental age into clinical practice. (3D-MALF - CE AVEC: 356/2018/Sper/IOR). Currently, extremely complex bone correction interventions are often planned and performed through Computer Aided Design (CAD) and 3D printing of models and custom sterilizable cutting guides (Patient-Specific Instrument, PSI). In pediatric orthopedic surgery is often necessary to use homologous massive bone grafts customized on the patient's anatomy, which can be employed in the replacement of neoplastic lesions, in the axial correction of deformities or even in the extemporaneous lengthening of bone segments. The Musculoskeletal Tissue Bank (BTM) regularly provides bone grafts processed in a Class A controlled contamination environment according to GMP (Clean Room), guaranteeing quality and microbiological safety. The current realization standard of bone grafts on specific request is a freehand realization. The BTM technicians model the grafts, based on the indications received (length, width, height, indications on geometry), using standard surgical instruments (osteotomes, oscillating saws, etc.). The present clinical trial aims to validate the feasibility, accuracy and effectiveness of an innovative process for producing customized bone allografts to correct bone deformities in children. the customization process will be conducted by using computer-aided surgical simulation and 3D printing.

Conditions

Musculoskeletal Deformity; Musculoskeletal Diseases; Musculoskeletal Disorder

Keywords

Bone allograft; 3D printing; Computer aided surgical simulation; Virtual surgical simulation; Orthopedics; Pediatrics; Additive Manufacturing; Cutting guides; 3D models

Outcome Measures

Primary Outcomes (2)

• allograft dimensions

  The main dimensions of the obtained graft (height, lenght and depth), which are also the most clinically significant, will be measured in millimiters in the clean-room. The analysis of the dimensions obtained will be performed reconstructing the CT images of the graft. These dimensions will be compared with those planned by VSP, in order to examine the accuracy, reliability, and repeatability of the graft processing through GSI compared to standard processing.

  The measurements will be collected during the first three years of the study.

• allograft volume

  The volume of the obtained graft will be measured in millimiters square in the clean-room. The analysis of the volumes obtained will be performed reconstructing the CT images of the graft. These values will be compared with those planned by VSP, in order to examine the accuracy, reliability, and repeatability of the graft processing through GSI compared to standard processing.

  The measurements will be collected during the first three years of the study.

Secondary Outcomes (9)

• cost analysis

  The cost analysis will be conducted during the first three years of the study.

• Geometrical-structural analysis of PSI and GSI

  The geometrical-structural analysis will be conducted during the first three years of the study.

• operating time

  The analysis will be conducted during the first three years of the study.

• Fluoroscopy time

  The analysis will be conducted during the first three years of the study.

• Intraoperative bleeding

  The analysis will be conducted during the first three years of the study.

Study Arms (2)

Standard Group

SHAM COMPARATOR

The main measures of the designed graft are extrapolated from VSP. The dimensioned drawings of the graft are delivered to the bone bank that prepares the graft according to standard procedures.

Device: Planning of multiplanar and/or multifocal osteotomies in children by using VSP, PSIs and customized structural bone allograft; Device: Routine preparation of bone graft according to standard protocols; Procedure: Corrective osteotomy

GSI Group

ACTIVE COMPARATOR

The main measures of the designed graft are extrapolated from VSP. The bone bank provides a series of CTs of bone segments from those available for processing. These bone segments are reconstructed and compared with the planning to find the best match. Once defined which bone segment will be used, if necessary, the planning is adapted to it.

Device: Planning of multiplanar and/or multifocal osteotomies in children by using VSP, PSIs and customized structural bone allograft; Device: Preparation of bone graft with virtual bone-matching and GSIs; Procedure: Corrective osteotomy

Interventions

Planning of multiplanar and/or multifocal osteotomies in children by using VSP, PSIs and customized structural bone allograft DEVICE

Preoperative VSP is performed starting from 3D digital models obtained from DICOM data of CT-scan with a segmentation process. If applicable, a model of the contralateral limb is obtained and used as reference for the correction. The surgeon and the engineer together define the surgical strategy, establishing the correction, the design of Patient-Specific Instruments (PSIs) and the hardware to implant. Then, through VSP, an ideal model of the bone graft is designed.

GSI Group; Standard Group

Routine preparation of bone graft according to standard protocols DEVICE

The size dimensions obtained through VSP are used by the tissue bank to manually cut a structural bone graft according to the standard protocols.

Standard Group

Preparation of bone graft with virtual bone-matching and GSIs DEVICE

The best donor bone is identified by matching the 3D models provided by bone bank with the planned graft, considering not only the size but also the most suitable configuration of cortical and medullary bone. Then GSIs are designed and 3D printed to perform the exact cut on the donor bone according to the experimental protocol.

GSI Group

Corrective osteotomy PROCEDURE

The acute surgical correction is performed according to VSP using PSI and the customized bone graft. Preoperative variables (age, sex, disease, deformity), intraoperative variables (operation time, intraoperative complications, use of fluoroscopy, intraoperative bleeding) are registered.

GSI Group; Standard Group

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• From 2 to 18 years old
• Diagnosis of limbs musculoskeletal diseases
• Need for uni- or poly-axial correction through one or more osteotomies
• Need for massive bone graft to stabilize the correction
• Consent to the processing of data

You may not qualify if:

• Patients who refuse the VSP study
• Patients who do not undergo in-depth radiological examinations or patients with insufficient radiological documentation
• Patients who undergo different interventions for the correction of musculoskeletal disease
• Patients who do not need a massive bone graft
• Pregnant women

Sponsors & Collaborators

• Istituto Ortopedico Rizzoli: lead
• University of Bologna: collaborator

Study Sites (1)

IRCCS - Istituto Ortopedico Rizzoli

Bologna, 40136, Italy

Location

Related Publications (15)

• Raza M, Murphy D, Gelfer Y. The effect of three-dimensional (3D) printing on quantitative and qualitative outcomes in paediatric orthopaedic osteotomies: a systematic review. EFORT Open Rev. 2021 Feb 1;6(2):130-138. doi: 10.1302/2058-5241.6.200092. eCollection 2021 Feb.

  PMID: 33828856 BACKGROUND

• Grassi FR, Grassi R, Vivarelli L, Dallari D, Govoni M, Nardi GM, Kalemaj Z, Ballini A. Design Techniques to Optimize the Scaffold Performance: Freeze-dried Bone Custom-made Allografts for Maxillary Alveolar Horizontal Ridge Augmentation. Materials (Basel). 2020 Mar 19;13(6):1393. doi: 10.3390/ma13061393.

  PMID: 32204393 BACKGROUND

• Frizziero L, Santi GM, Leon-Cardenas C, Ferretti P, Sali M, Gianese F, Crescentini N, Donnici G, Liverani A, Trisolino G, Zarantonello P, Stallone S, Di Gennaro GL. Heat Sterilization Effects on Polymeric, FDM-Optimized Orthopedic Cutting Guide for Surgical Procedures. J Funct Biomater. 2021 Nov 19;12(4):63. doi: 10.3390/jfb12040063.

  PMID: 34842761 BACKGROUND

• Frizziero L, Santi GM, Leon-Cardenas C, Donnici G, Liverani A, Papaleo P, Napolitano F, Pagliari C, Di Gennaro GL, Stallone S, Stilli S, Trisolino G, Zarantonello P. In-House, Fast FDM Prototyping of a Custom Cutting Guide for a Lower-Risk Pediatric Femoral Osteotomy. Bioengineering (Basel). 2021 May 26;8(6):71. doi: 10.3390/bioengineering8060071.

  PMID: 34073324 BACKGROUND

• Ferretti P, Leon-Cardenas C, Santi GM, Sali M, Ciotti E, Frizziero L, Donnici G, Liverani A. Relationship between FDM 3D Printing Parameters Study: Parameter Optimization for Lower Defects. Polymers (Basel). 2021 Jun 30;13(13):2190. doi: 10.3390/polym13132190.

  PMID: 34209372 BACKGROUND

• Frizziero L, Pagliari C, Donnici G, Liverani A, Santi GM, Papaleo P, Napolitano F, Leon-Cardenas C, Trisolino G, Zarantonello P, Di Gennaro GL, Stilli S, Stallone S. Effectiveness Assessment of CAD Simulation in Complex Orthopedic Surgery Practices. Symmetry. 2021; 13(5):850.

  BACKGROUND

• Frizziero L, Santi GM, Liverani A, Napolitano F, Papaleo P, Maredi E, Gennaro GLD, Zarantonello P, Stallone S, Stilli S, Trisolino G. Computer-Aided Surgical Simulation for Correcting Complex Limb Deformities in Children. Applied Sciences. 2020; 10(15):5181.

  BACKGROUND

• Osti F, Santi GM, Neri M, Liverani A, Frizziero L, Stilli S, Maredi E, Zarantonello P, Gallone G, Stallone S, Trisolino G. CT Conversion Workflow for Intraoperative Usage of Bony Models: From DICOM Data to 3D Printed Models. Applied Sciences. 2019; 9(4):708.

  BACKGROUND

• Frizziero L, Santi GM, Liverani A, Giuseppetti V, Trisolino G, Maredi E, Stilli S. Paediatric Orthopaedic Surgery with 3D Printing: Improvements and Cost Reduction. Symmetry. 2019; 11(10):1317.

  BACKGROUND

• Frizziero L, Santi GM, Leon-Cardenas C, Donnici G, Liverani A, Napolitano F, Papaleo P, Pagliari C, Antonioli D, Stallone S, Di Gennaro GL, Trisolino G, Zarantonello P. An Innovative and Cost-Advantage CAD Solution for Cubitus Varus Surgical Planning in Children. Applied Sciences. 2021; 11(9):4057.

  BACKGROUND

• Kim HJ, Yoo SY, Jeon TY, Kim JH. Model-based iterative reconstruction in ultra-low-dose pediatric chest CT: comparison with adaptive statistical iterative reconstruction. Clin Imaging. 2016 Sep-Oct;40(5):1018-22. doi: 10.1016/j.clinimag.2016.06.006. Epub 2016 Jun 16.

  PMID: 27348057 BACKGROUND

• Chiesa AM, Spinnato P, Miceli M, Facchini G. Radiologic Assessment of Osteosarcoma Lung Metastases: State of the Art and Recent Advances. Cells. 2021 Mar 4;10(3):553. doi: 10.3390/cells10030553.

  PMID: 33806513 BACKGROUND

• Meyer S, Hirsch JM, Leiggener CS, Msallem B, Sigron GR, Kunz C, Thieringer FM. Fibula Graft Cutting Devices: Are 3D-Printed Cutting Guides More Precise than a Universal, Reusable Osteotomy Jig? J Clin Med. 2020 Dec 20;9(12):4119. doi: 10.3390/jcm9124119.

  PMID: 33419329 BACKGROUND

• Zelen M. The randomization and stratification of patients to clinical trials. J Chronic Dis. 1974 Sep;27(7-8):365-75. doi: 10.1016/0021-9681(74)90015-0. No abstract available.

  PMID: 4612056 BACKGROUND

• Thibault, JB. Veo: CT Model-Based Iterative Reconstruction. 2010. Available online: http://www.gehealthcare.com

  BACKGROUND

MeSH Terms

Conditions

Musculoskeletal Diseases

Study Officials

• Giovanni Trisolino, MD

  IRCCS - Istituto Ortopedico Rizzoli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Both the doctor and the patient will not be aware of the graft preparation method.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study in defined as a randomized clinical trial with two groups and will be double-blind. The randomization will be based on the realization method of the grafts.

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: January 26, 2023
• Study Start: June 1, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: The data will be kept by the principal investigator for the time necessary for scientific production.
• Access Criteria: IPD available on request due to restrictions. The IPD presented in this protocol could be available on request from the principal investigator. The data are not publicly available due to national privacy regulations.

Locations

IT (1)