3D Printing An Innovative Technology for Medicine Ing. Stefania - - PowerPoint PPT Presentation

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3D Printing An Innovative Technology for Medicine Ing. Stefania - - PowerPoint PPT Presentation

3D Printing An Innovative Technology for Medicine Ing. Stefania Marconi, PhD Dept. of Civil Engineering and Architecture University of Pavia 3D4MED: the Lab 3D4MED is the first Clinical 3D Printing Lab in Italy and one of the first worldwide.


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3D Printing

An Innovative Technology for Medicine

  • Ing. Stefania Marconi, PhD
  • Dept. of Civil Engineering and Architecture

University of Pavia

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3D4MED: the Lab 3D4MED is the first Clinical 3D Printing Lab in Italy and

  • ne of the first worldwide.

It is located at the DEA building of IRCCS Policlinico San Matteo of Pavia and it has a strategic position to improve its visibility (to disseminate the new proposed service) and centrality (to facilitate the collaboration between surgeons and engineers). DEA Building 0 floor – tower B 3D4MED Lab

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3D4MED: the Lab

3D4MED is equipped with all the hardware and software necessary to perform the entire process, from medical images elaboration to the production of the 3D printed model. We are equipped with: ➢ Image elaboration and segmentation software; ➢ Software for virtual models’ manipulation; ➢ 3D printers management software; ➢ Professional 3D printers; ➢ Post-processing instrumentation.

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3D4MED: the Idea

We transform medical images (CT & MRI) into a 3D printed object to hold in your hands!

A new technology for an effective and customized surgery!

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3D4MED: How?

Virtual Model Slicing 3D Printed Model Thanks to innovative 3D printing technologies, we produce three-dimentional replicas of each patient’s unique anatomy, showing all the surgical relevant structures accurately.

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3D4MED: the Lab

The Lab is equipped with different 3D printing technologies:

3DSystems ProJet 460 Plus

➢ Binder jetting technology; ➢ High precision (100 μm) and low production times and costs; ➢ 2.8 milion colors; ➢ Big/small models with fine details, especially bone structures;

ObJet 260 Connex 3

➢ PolyJet printer with photopolymer resins; ➢ Different colors & materials (deformable and transparent); ➢ Big/small models with fine details (20 μm); ➢ 3D printed models of the abdominal cavity;

FORM 2 Desktop SLA

➢ Printer with photopolymer resins; ➢ High precision (100/50/25 μm); ➢ 4 different transparent materials (1 deformable); ➢ Medium/small (vascular) models with fine details;

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Available 3D Printers

3NTR A4v2

➢ Professional FDM printer; ➢ Dual bowden extruder (water cooled extruders up to 410°C);

LeapFrog Creatr HS

➢ FDM printer; ➢ Dual bowden extruder; ➢ Suitable for relatively high speeds printing of large objects;

LeapFrog Creatr Dual Extruder

➢ FDM printer; ➢ Dual direct extruder; ➢ Suitable for low modulus filaments printing;

3NTR A4v3

➢ Professional FDM printer; ➢ Triple bowden extruder (water cooled extruders up to 410°C); ➢ Hot chamber (up to 70°C);

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Renishaw AM 400

➢ SLM metal 3D printer; ➢ Flexible AM for professional use in a wide range of metals; ➢ 400W optical system with a reduced beam diameter of 70 μm; ➢ Available metal powders: Titanium, Aluminium, Cobalt chromium, Stainless steel, Nickel alloys.

Instrumentation for post-processing treatments:

➢ Heat treatments oven; ➢ Sandblasting machine; ➢ Machining center for finishing and removal.

Available 3D Printers

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3D Printing Applications in Medicine

3D Printed ORGAN MODELS 3D Printed IMPLANTS 3D Printed DRUGS

BIOPRINTING

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3D Printing Applications in Medicine

3D Printed Patient - Specific ORGAN MODELS

Applications: Surgical Planning Surgical Simulation Intra-Operative Guide Medical Training Informed Consent

Anatomical Comprehension

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3D Printing Applications in Medicine

3D Printed Patient - Specific ORGAN MODELS

Available Materials & Technologies: Photopolymer Resins

➢ Material Jetting ➢ Stereolithography

Chalk Powder

➢ Binder Jetting

Thermoplastic Polymers

➢ Fused Deposition Modeling (FDM)

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3D Printing Applications in Medicine

3D Printed Patient – Specific IMPLANT & PROSTHESIS

Applications: Permanent Implants Orthopedic Braces Prosthesis & Orthosis Dental Implants Artificial Joints Maxillo - Facial Plates

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3D Printing Applications in Medicine

3D Printed Patient - Specific IMPLANT & PROSTHESIS

Available Materials & Technologies: Metals

➢ SLM ➢ SLS

Ceramic Materials

➢ SLS ➢ Material Jetting

Thermoplastic Polymers

➢ Fused Deposition Modeling (FDM)

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3D Printing Applications in Medicine

3D Printed Parts for REGENERATIVE MEDICINE

Applications: Biodegradable Scaffolds BioPrinting Tissue Engineering ➢ Biocompatible ThermoPolymers (i.e. PCL, PLA, PVA…) ➢ Natural Biomaterials (i.e. Chitosan, Collagen, Fibrin…) ➢ Natural Hydrogel (i.e. Alginate, Gelatine…) Available Materials & Technologies: ➢ Commercial Bioplotter ➢ Fused Deposition Modeling (FDM)

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3D Printing Applications in Medicine

3D Printed DRUGS

Applications: Customized Drugs PolyPills On-Demand Production ➢ Increased complexity of drugs ➢ Customization based on patient’s mass and metabolism ➢ Polypill production: tablet containing more active pharmaceutical ingredients simultaneously Available Technologies: ➢ Stereolithography (SLA) ➢ Extrusion Systems & Fused Deposition Modeling (FDM) ➢ Binder Jetting & Binder Deposition Advantages:

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3D Printing Applications in Medicine

3D Printed ORGAN MODELS 3D Printed IMPLANTS 3D Printed DRUGS

BIOPRINTING

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3D4MED: Specialties

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3D4MED: Clinical Cases

Thoracic Surgery

Pulmonary Pathology Treatment

The 3D printed patient-specific model represents the cardio-pulmonary tract affected by a pulmonary pathology. The model has been useful for the pre-

  • perative planning of the pulmonary

pathology treatment and the evaluation

  • f the systemic arteries involvement.
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3D4MED: Clinical Cases

Thoracic Surgery

Supra–Aortic Pulmonary Pathology

The 3D printed patient-specific model represents the cardio-pulmonary and supra- aortic tracts affected by a pulmonary pathology. The model has been useful for the pre-

  • perative planning of the pulmonary

pathology treatment and the evaluation of the systemic arteries involvement. Pulmonary arteries Aortic Arch Pulmonary veins Systemic arteries Pathology

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3D4MED: Clinical Cases

Thoracic Surgery

Supra–Mammary Pathology Treatment

The 3D printed patient-specific model represents the supra-mammary anatomical district affected by an extended pulmonary pathology. The model has been useful for the pre-

  • perative planning of the pulmonary pathology

treatment and the evaluation of the systemic arteries involvement The green part represents the pulmonary pathology, extended even outside the rib cage.

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3D4MED: Clinical Cases

Thoracic Surgery

Pericardic Inflammation Evaluation

The model has been used to properly plan the surgical treatment

  • f a pericardic

inflammation due to the damage of metallic staples previously implanted in the sternum.

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3D4MED: Clinical Cases

Thoracic Surgery

Severe Pulmonary Pathology

The 3D printed patient-specific model represents the thoracic anatomical district affected by an extended neoplasm pathology. The model has been useful for the pre-

  • perative planning of the pulmonary pathology

treatment and the evaluation of the systemic arteries involvement The green part represents the pulmonary pathology, extended even outside the rib cage.

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3D4MED: Clinical Cases

Kidney tumor resection: robotic resection planned on the 3D printed model. Models for spleen laparoscopic resection and splenic artery aneurysm esclusion.

Deformable materials used to simulate the surgery

Abdominal Surgery

Interlocking parts, to assess tumor relation with surrounding structures.

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3D4MED: Clinical Cases

Abdominal Surgery

Phantom for the surgical simulation of living-donor kidney transplantation procedure

  • Arterial system;
  • Venous system;
  • Pelvic bones;
  • Bladder;
  • Ureters;
  • Psoas and iliac muscles;
  • Abdominal muscles;
  • Skin;

Patient-specific parts (arteries, veins and bladder) to be change for the simulation of the specific clinical case

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3D4MED: Clinical Cases

Cardio-Vascular Surgery

Left heart cavity reconstruction.

The model has been used to plan surgical access from pulmonary arteries to the point of interest.

3D Virtual Model 3D Printed Model Placement of aortic endoprosthesis 3D printed models influence the choice of the type and geometry of the most suitable endoprosthesis for the particular clinical case.

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3D4MED: Clinical Cases

Cardio-Vascular Surgery

Pulmonary arteries

The model has been used to plan surgical access from pulmonary arteries to the point of interest.

Cardiology

Left Atrial Appendage Closure

The model has been useful to properly plan and simulate trans- catheter closure feasibility.

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3D4MED: Clinical Cases

Orthopedics

Reconstruction of spine, vessels and spine tumor. Interlocking parts (vertebra), to assess tumor visibility and its relation with surrounding structures. Spine Interlocking vertebra Tumor visibility Pre - operative evaluation of foot fracture. 3D models of traumatic injuries are required with considerable urgency; we are able to produce them within 12 hours.

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3D4MED: Clinical Cases

Orthopedics

Pelvis Fracture Evaluation

The model has been useful to evaluate the degree of the compound fracture, the bones to be reconstructed and the presence of bone fragments.

Scoliosis & Spine Tumor Treatment

The model has been useful to evaluate the pathological curvature

  • f the spine and to plan

the surgical treatment involving the modeling and the placement of metal bars to straighten the spinal column. The model has been useful to properly plan the spine tumor complex resection caused by the worsening of patient’s scoliosis.

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3D4MED: Clinical Cases

Otolaryngology

Temporal bones thickness map and ear/scalp reconstruction to be used for surgical planning and access evaluation.

  • Red → high thickness
  • Green → medium thickness
  • Blue → low thickness

Complete positioning system for fixing bone fragments for dissection exercise and surgical training in otolaryngology.

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3D4MED: Clinical Cases

Otolaryngology

Temporal bones 3D printed models can be also used to design metal surgical guides. Temporal bone chalk powder 3D model – to mimic natural bones’ mechanical properties – and 3D printed steel surgical guide 3D printed salivary ducts’ models – both normal and pathological – for the simulation of surgical unblocking procedures.

Normal Submandibular Salivary duct stone Stenosis

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3D4MED: Clinical Cases

NeuroSurgery

Left middle cerebral artery aneurysm clipping

The model has been for the simulation of the aneurysm clipping

  • procedure. The aneurysm, its

vascular proximal tract and the thrombus have been 3D printed in soft material with different degree of deformability to assure the best adherence with the physiological reality.

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3D Printing Applications in Medicine

3D Printed Parts for REGENERATIVE MEDICINE

Applications: Biodegradable Scaffolds BioPrinting Tissue Engineering ➢ Biocompatible ThermoPolymers (i.e. PCL, PLA, PVA…) ➢ Natural Biomaterials (i.e. Chitosan, Collagen, Fibrin…) ➢ Natural Hydrogel (i.e. Alginate, Gelatine…) Available Materials & Technologies: ➢ Commercial Bioplotter ➢ Fused Deposition Modeling (FDM)

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Regenerative Medicine: the Process

Thermoplastic biocompatible polymers (PLA & PCL) Setting of printing parameters and 3D printing Implant Incubation Implant Transfer

Biocompatible materials for implantable scaffolds and 3D printing

Stem Cells from Adipose Tissue Implant Seeding

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Produce a copolymeric PLA-PCL patch for esophageal tissue regeneration Thermoplastic biocompatible polymers PCL (polycaprolactone) PLA (polylactic acid) Setting of printing parameters and 3D printing Final esophageal patches Biological analysis and mechanical characterizatio n

In collaboration with: Prof. Bice Conti & Drug Science Department

Biocompatible materials for implantable scaffolds and 3D printing

Regenerative Medicine: the Process

  • R. Dorati, A. De Trizio, S. Marconi, A. Ferrara, F. Auricchio, I. Genta, T. Modena, M. Benazzo, A. Benazzo, G. Volpato, B.Conti. Design of a Bioabsorbable

Multilayered Patch for Esophageal Tissue Engineering, Macromolecular Bioscience, vol.17 (6) (2017).

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Goal : to find a compromise between biological and mechanical responses

Biocompatible materials for implantable scaffolds and 3D printing

Regenerative Medicine: Performed Tests

Porosity variations by changing infill percentage To find the most suitable porosity for the esophageal patch SEM Analysis: to determinate internal structure and morphology GPC Analysis: to determinate the Molecular Weight

  • f polymers

MTT Analysis: to determinate cell viability and proliferation Information about morphological aspects How polymer Mw changes after the extrusion process Analyse cell viability and engraftment on 3D printed patches Mechanical characterization: to determinate 3D printed patches’ stiffness To reproduce esophageal tissue mechanical features

Biological Tests

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3D networks made

  • f biocompatible

thermoplastic polymers

Hydrogels Cells Bioink Bioprinting

Biological components (cells) are encapsulated in hydrogels Used in biomedical and tissue engineering applications Layer by layer deposition of bioink

Bioink Bioplotter (Future) Tissue

Bioprinting: the Process

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Bioprinting: Tested Cells & Materials

Natural hydrogel Synthetic

Tested Material Alginate and Gelatin Chitosan PCL HIPE Application

Evaluate printing process of HeLa, cell model of SH- SY5Y, 3D model

  • f neuromuscolar

junctions (iPSCs) and of muscle fiber (C2C12).

(Collab. Ist. Mondino)

Encapsulate fibroblast cell line for tissue regeneration

(Collab. Chemical dept., UniPV)

Reinforce PCL with HA to realized scaffolds for

  • steoblast

culture

(Master thesis, collab. Federico II, Naples)

Produce tall, complex scaffolds with an internal lattice structure and microscale porosity

(Collab. Chemical dept., UniPV)

Test Viability and proliferation Material printability Material characterization Material printability Preliminary Results Good proliferation, biocompatibility and major cell viability Not suitable for printing process PCL is able to be printed using Cellink INKREDIBLE+ Not suitable for printing process

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Bioprinting: Some Examples

Cellink INKREDBLE + Cellink Start: soluble support material (CellInk patented) 6%Sodium-Alginate + 4%Gelatin + 0,4%CalciumChloride

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Other Activities: ECCS ExtraCorporeal Circulator Simulator

HEATER OXYGENATOR GAS BLENDER RESERVOIR AORTA 3D PRINTED MODEL ACQUISITION CENTRIFUGAL PUMP AND CONTROLLER

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Other Activities: ECCS Medical devices to be tested in our circuit:

Oxygenators Ventricular Assist Devices Anatomical 3D models Dialyzers Blood pumps Gas Blenders

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Other Activities: Modular Flow Chamber

Goal: Development of a modular chamber design, rapid to manufacture by 3D printing and easy to manage, to

hold a silk-based 3D sponge with interconnected/controlled-size pores and able to support platelets formation for bone marrow tissue engineering. Supported scaffold – 3D printed mold Cover top – 3D printed mold Supported scaffold – Silicon model Cover top – Silicon model Closed & lock Silk sponge perfused

  • The new system reproduces the basic features of the 3D bone marrow structure;
  • Platelets collected after perfusion show the same morphology as peripheral blood platelets;
  • Collected platelets express fibronectin, thrombospondin and vWF, proteins normally present in platelet

granules;

  • The combination of 3D printed scaffolds with silk biomaterial allows the development of a versatile platform

for ex vivo platelet production.

  • C. A. Di Buduo, P.M. Soprano, L. Tozzi, S. Marconi, F. Auricchio, D. L. Kaplan, A. Balduini. Modular flow chamber for engineering bone marrow architecture

and function, Biomaterials, Aug 2017, 146 60-71.

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Thanks for Your Attention

More information about our activities can be found on our WebSite and Social Networks! www.3d4med.eu 3d4med@unipv.it 3D4MED 3d4med

  • Ing. Stefania Marconi, PhD

stefania.marconi@unipv.it