Advanced Surgical Simulation Processes in the Correction of Skeletal Defects and Deformities (SIMULA)

Virtual Surgical Planning (VSP), Computer-Aided Surgical Simulation (CASS) for bone corrections, and the customization of implants and devices through 3D printing, known as Patient-Specific Instruments (PSI) and Graft-Specific Instruments (GSI), are assuming increasingly central roles in orthopedic clinical and surgical practice.

One area witnessing notable advancement is the treatment of musculoskeletal disorders (MMS) in children, adolescents, and young adults. These disorders involve severe and rare abnormalities in skeletal formation and development across three-dimensional planes, often affecting multiple limbs. Managing such deformities is complex, challenging to standardize, and prone to unpredictable clinical, radiographic, and functional outcomes.

The application of 3D modeling and printing technologies offers a deeper understanding of deformities and facilitates improved prediction, precision, reproducibility, and safety in surgical interventions.

The Musculoskeletal Apparatus Network (RAMS Network) centers are equipped with advanced 3D laboratories for surgical simulation and planning, aligned with the overarching goal of improving surgery quality through "in-silico" medicine (ISM) principles.

At present, numerous complex surgeries involving Virtual Surgical Planning (VSP) and sterilizable 3D-printed Patient-Specific Instruments (PSI) and/or Graft-Specific Instruments (GSI) are being simulated and performed at the Rizzoli Institute. Preliminary data from previous protocols indicate a significant reduction in surgical time with the implementation of VSP and the utilization of PSI and GSI.

The aim of this study is to enhance the current process of simulating, planning, and designing surgical support tools within 3D Printing Point-of-Care (3D POC) facilities. To achieve this, it is imperative to expand case volumes and systematically organize, categorize, and standardize simulation and planning procedures.

Study Overview

• Status: Recruiting
• Conditions: Musculoskeletal Abnormalities; Musculoskeletal Disorder; Musculoskeletal Deformity
• Intervention / Treatment: Procedure: Deformity correction

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Grazia Chiara Menozzi; Phone Number: 484 0516366; Email: graziachiara.menozzi@ior.it
• Study Contact Backup: Name: Giovanni Trisolino, MD; Phone Number: 484 0516366; Email: giovanni.trisolino@ior.it

Study Locations

• Italy
  • Genova, Italy
    • Not yet recruiting
    • Istituto Giannina Gaslini
    • Contact: Giorgio Marrè Brunenghi, MD; Email: giorgiomarre@gaslini.org
  • Milan, Italy
    • Not yet recruiting
    • Galeazzi Orthopedic Institute
    • Contact: Fabio Verdoni, MD; Email: fabio.verdoni@grupposandonato.it
  • Pavia, Italy
    • Not yet recruiting
    • Policlinico San Matteo
    • Contact: Gianluigi Pasta, MD
  • Roma, Italy
    • Not yet recruiting
    • Istituto Nazionale Tumori Regina Elena
    • Contact: Roberto Biagini, MD; Email: roberto.biagini@ifo.it
  • Roma, Italy
    • Not yet recruiting
    • Ospedale Pediatrico Bambino Gesu
    • Contact: Pier Francesco Costici, MD; Email: pierfrancesco.costici@opbg.net
  • BO
    • Bologna, BO, Italy, 40136
      • Recruiting
      • IRCCS Istituto Ortopedico Rizzoli
      • Contact: Grazia Chiara Menozzi; Phone Number: 484 0516266; Email: graziachiara.menozzi@ior.it
  • MI
    • Rozzano, MI, Italy
      • Not yet recruiting
      • Istituto Clinico Humanitas
      • Contact: Tommaso Bonanzinga, MD; Email: tommaso.bonanzinga@hunimed.eu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of musculoskeletal disease (MSD) of the limbs;
• Need for mono- or polyaxial correction by one or more osteotomies;
• Presence of specific consent to participate in the trial;

Exclusion Criteria:

• Patients who refuse to participate in the study
• Patients who do not undergo radiological follow-up examinations for VSP or for whom the radiological record is insufficient to conduct VSP;
• Patients who undergo different interventions for correction of MSD (growth modulation interventions by epiphysiodesis and hemiepiphysiodesis, progressive correction by external circular/hexapodal fixation);
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pediatric patients with musculoskeletal diseases; Children, adolescents, and young adults suffering from musculoskeletal disorders (MMD) who exhibit complex conditions characterized by rare and severe anomalies in skeletal development. These abnormalities may affect bones, joints, and musculotendinous structures.	Procedure: Deformity correction; Surgeries to correct bone defomity, supported by the use of preoperative planning and/or patient-specific instruments

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achieved skeletal corrections	Assessment of achieved skeletal corrections compared to planned corrections, measured on standard radiographs or CT scans depending on the type of deformity corrected	At baseline (day 0)
Achieved skeletal corrections	Assessment of achieved skeletal corrections compared to planned corrections, measured on standard radiographs or CT scans depending on the type of deformity corrected	After 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Operating room times	Operating room times for each planned procedure	At baseline (day 0)
Fluoroscopy times	Fluoroscopy times for each planned procedure	At baseline (day 0)
Blood loss	Blood loss for each patient	At baseline (day 0)
Intra- and peri-operative complications	Intra- and peri-operative complications for each patient	At baseline (day 0)
Suitability of PSIs	Suitability of PSIs in relation to the planned surgery	At baseline (day 0)
Suitability of GSIs	Suitability of GSIs, if needed, in relation to the planned surgery	At baseline (day 0)
Suitability of bone graft	Suitability of bone graft, if needed, in relation to the planned surgery	At baseline (day 0)
Clinical-functional outcome	Clinical-functional outcome will be assessed by preoperative and one-year follow-up administration of the Pediatric Outcome Data Collection Instrument (PODCI) questionnaire for pediatric patients or the Short Form Health Survey 36 (SF-36) for young adults	At baseline (day 0)
Clinical-functional outcome	Clinical-functional outcome will be assessed by preoperative and one-year follow-up administration of the Pediatric Outcome Data Collection Instrument (PODCI) questionnaire for pediatric patients or the Short Form Health Survey 36 (SF-36) for young adults	After 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost analysis	The cost analysis will entail evaluating expenses associated with various components, including imaging required for planning, production of 3D-printed instrumentation such as PSIs and GSIs, and bone grafts. Additionally, human costs for planning will be considered. Surgical-related costs will be assessed by comparing them with those of traditional surgeries to gauge the cost-effectiveness of the procedure, taking into account the achieved correction and the necessity for additional procedures.	At baseline (day 0)

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Rizzoli
• Collaborators: Istituto Clinico Humanitas; Istituto Giannina Gaslini; Ospedale Pediatrico Bambino Gesù; Galeazzi Orthopedic Institute; Istituto Nazionale Tumori Regina Elena; Policlinico San Matteo
• Investigators: Principal Investigator: Pierfrancesco Costici, MD, Ospedale Pediatrico Bambin Gesù; Principal Investigator: Giorgio Marrè Brunenghi, MD, Istituto Giannina Gaslini; Principal Investigator: Fabio Verdoni, MD, Galeazzi Orthopedic Institute; Principal Investigator: Roberto Biagini, MD, Istituto Nazionale Tumori Regina Elena; Principal Investigator: Gianluigi Pasta, MD, Policlinico San Matteo; Principal Investigator: Tommaso Bonanzinga, MD, Istituto Clinico Humanitas

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• R. Michaels et al., "3D printing in surgical simulation: emphasized importance in the COVID-19 pandemic era," https://doi.org/10.2217/3dp-2021-0009, vol. 5, no. 1, pp. 5-9, May 2021, doi: 10.2217/3DP-2021-0009.
• S. Dash, S. K. Shakyawar, M. Sharma, and S. Kaushik, "Big data in healthcare: management, analysis and future prospects," J Big Data, vol. 6, no. 1, pp. 1-25, Dec. 2019, doi: 10.1186/S40537-019-0217-0/FIGURES/6.
• G. Pravettoni and S. Triberti, "A 'P5' Approach to Healthcare and Health Technology," P5 eHealth: An Agenda for the Health Technologies of the Future, pp. 3-17, 2020, doi: 10.1007/978-3-030-27994-3_1.
• Anaya JM, Duarte-Rey C, Sarmiento-Monroy JC, Bardey D, Castiblanco J, Rojas-Villarraga A. Personalized medicine. Closing the gap between knowledge and clinical practice. Autoimmun Rev. 2016 Aug;15(8):833-42. doi: 10.1016/j.autrev.2016.06.005. Epub 2016 Jun 11.
• Coppola L, Cianflone A, Grimaldi AM, Incoronato M, Bevilacqua P, Messina F, Baselice S, Soricelli A, Mirabelli P, Salvatore M. Biobanking in health care: evolution and future directions. J Transl Med. 2019 May 22;17(1):172. doi: 10.1186/s12967-019-1922-3.
• Pop B, Fetica B, Blaga ML, Trifa AP, Achimas-Cadariu P, Vlad CI, Achimas-Cadariu A. The role of medical registries, potential applications and limitations. Med Pharm Rep. 2019 Jan;92(1):7-14. doi: 10.15386/cjmed-1015. Epub 2019 Jan 15.
• Dorsey ER. The new platforms of health care. NPJ Digit Med. 2021 Jul 15;4(1):112. doi: 10.1038/s41746-021-00478-5.
• Tumiene B, Graessner H, Mathijssen IM, Pereira AM, Schaefer F, Scarpa M, Blay JY, Dollfus H, Hoogerbrugge N. European Reference Networks: challenges and opportunities. J Community Genet. 2021 Apr;12(2):217-229. doi: 10.1007/s12687-021-00521-8. Epub 2021 Mar 17.
• Vivarelli L, Govoni M, Attala D, Zoccali C, Biagini R, Dallari D. Custom Massive Allograft in a Case of Pelvic Bone Tumour: Simulation of Processing with Computerised Numerical Control vs. Robotic Machining. J Clin Med. 2022 May 15;11(10):2781. doi: 10.3390/jcm11102781.
• Benedetti MG, et al. Prot. CHILD-DEROT. 'Studio pilota per la pianificazione del trattamento alterazioni torsionali dell'arto inferiore nei bambini affetti da paralisi cerebrale infantile mediante valutazione integrata morfologica e funzionale.' CE AVEC 718/2021/Oss/IOR. 30/09/2021.
• L. Frizziero et al., "Computer-aided surgical simulation for correcting complex limb deformities in children," Applied Sciences (Switzerland), vol. 10, no. 15, Aug. 2020, doi: 10.3390/app10155181.
• L. Frizziero et al., "Paediatric orthopaedic surgery with 3D printing: Improvements and cost reduction," Symmetry (Basel), vol. 11, no. 10, Oct. 2019, doi: 10.3390/sym11101317.
• L. Frizziero et al., "An innovative and cost-advantage cad solution for cubitus varus surgical planning in children," Applied Sciences (Switzerland), vol. 11, no. 9, May 2021, doi: 10.3390/app11094057.
• "3D-MALF: 'Modelli 3D-printing nel planning preoperatorio del paziente pediatrico affetto da malformazioni congenite. Studio pilota.' - CE AVEC: 356/2018/Sper/IOR".
• "3D-MALF II: 'Innesti ossei personalizzati mediante analisi tridimensionale nelle deformità scheletriche in età pediatrica' - CE AVEC: 301/2022/Sper/IOR."
• L. Frizziero et al., "New Methodology for Diagnosis of Orthopedic Diseases through Additive Manufacturing Models," Symmetry 2019, Vol. 11, Page 542, vol. 11, no. 4, p. 542, Apr. 2019, doi: 10.3390/SYM11040542.
• L. Frizziero et al., "Effectiveness assessment of CAD simulation in complex orthopedic surgery practices," Symmetry (Basel), vol. 13, no. 5, May 2021, doi: 10.3390/sym13050850.
• F. Osti et al., "CT conversion workflow for intraoperative usage of bony models: From DICOM data to 3D printed models," Applied Sciences (Switzerland), vol. 9, no. 4, Feb. 2019, doi: 10.3390/app9040708.
• G. Durastanti, C. Belvedere, M. Ruggeri, D. M. Donati, B. Spazzoli, and A. Leardini, "A Pelvic Reconstruction Procedure for Custom-Made Prosthesis Design of Bone Tumor Surgical Treatments," Applied Sciences 2022, Vol. 12, Page 1654, vol. 12, no. 3, p. 1654, Feb. 2022, doi: 10.3390/APP12031654.
• Alessandri G, Frizziero L, Santi GM, Liverani A, Dallari D, Vivarelli L, Di Gennaro GL, Antonioli D, Menozzi GC, Depaoli A, Rocca G, Trisolino G. Virtual Surgical Planning, 3D-Printing and Customized Bone Allograft for Acute Correction of Severe Genu Varum in Children. J Pers Med. 2022 Dec 12;12(12):2051. doi: 10.3390/jpm12122051.
• Archunan MW, Petronis S. Bone Grafts in Trauma and Orthopaedics. Cureus. 2021 Sep 4;13(9):e17705. doi: 10.7759/cureus.17705. eCollection 2021 Sep.
• Depaoli A, Menozzi GC, Di Gennaro GL, Ramella M, Alessandri G, Frizziero L, Liverani A, Martinelli D, Rocca G, Trisolino G. The Flipping-Wedge Osteotomy: How 3D Virtual Surgical Planning (VSP) Suggested a Simple and Promising Type of Osteotomy in Pediatric Post-Traumatic Forearm Deformity. J Pers Med. 2023 Mar 19;13(3):549. doi: 10.3390/jpm13030549.
• Customized Bone Allografts by 3D-printing - Full Text View - ClinicalTrials.gov." https://classic.clinicaltrials.gov/ct2/show/NCT05700526?term=malf&cntry=IT&draw=2&rank=1 (accessed Aug. 21, 2023)

Helpful Links

• Customized Bone Allografts by 3D-printing (3D-MALF 2 protocol)

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 18, 2024
• First Submitted That Met QC Criteria: April 23, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pediatric Orthopedics; Virtual Surgical Planning; Patient-Specific instrument; Graft-Specific instrument
• Additional Relevant MeSH Terms: Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Musculoskeletal Diseases; Musculoskeletal Abnormalities
• Other Study ID Numbers: SIMULA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No