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1 Current and Future Uses of Additive Manufacturing in Neurologic, Musculoskeletal, Spinal, and Oncologic Surgery Michael J. Yaszemski, M.D., Ph.D. John & Posy Krehbiel Endowed Professor of Orthopedic Surgery and Biomedical Engineering Jane Matsumoto, M.D. Professor of Radiology Mayo Clinic, Rochester, MN National Science Foundation Arlington, VA March 17, 2016 Disclosure-Yaszemski Mayo Clinic and Dr. Yaszemski hold patents for various biodegradable polymers for use in musculoskeletal system repair. Grant support from NIH, DOD, Mayo Foundation, and the Krehbiel Professorship Associate Editor, Journal of Biomedical Materials Research-Part A Associate Editor, Techniques in Orthopaedics Consultant, Medtronic, Inc. & K2M, Inc. Page 1
2 Disclosure-Matsumoto Institutional: Mayo Clinic holds patents for various biodegradable polymers for use in musculoskeletal system repair. Custom Implant Bioprinting Custom Cutting Guide Surgical Planning Medical Education Patient Education Cell Scaffolding: Regenerative Medicine Research: MR, CT, US Forensic: Pathology Anatomic Models Laser Stereolithography Selective Laser Sintering Electrospinning Piezo- or Thermal Ink Jet Printing Custom Stent Sizing Fused Deposition Modeling Injection Moulding Polymeric & Cellular Bioprinting Page 2
3 Outline Current uses of additive manufacturing in medicine and surgery Illustrative examples Gaps in clinical care that might be addressed by additive technologies Research needs Future vision Tissue Engineering Strategy Scaffold Bioactive Molecules Cells Page 3
4 Scaffolds Polymers Natural: Silk, chitosan, alginate, collagen, decellularized allograft Synthetic: Polyesters, polyphosphazines, polyanhydrides, polyurethanes Metals Ceramics Scaffold 3D Fabrication by Injection Molding Page 4
5 Fused Deposition Modeling (Thermoplastic Extrusion) Fused Deposition Modeling Page 5
6 Fiber Electrospinning Scaffold Fabrication by Stereolithography Making model and STL file Making support and slicing Post-processing and curing Photo-crosslinking in SLA Page 6
7 Stereolithography (SLA) Layer-based fabrication technique using UV laser to polymerize resins Pore morphology (SEM) 913 µm 778 µm 670 µm 582 µm 508 µm 446 µm Top Side (* Bar represents 400 µm) Page 7
8 Bimodal Porosity in Scaffold Gelatin microsphere (for small pores: 20 ~ 50 µm) Solid freeform fabrication Leaching out microsphere PPF + cross-linker + initiator + accelerator Large pores (from CAD): 600 µm Small pores Scaffold Fabrication by 3D Thermal or Piezo Inkjet Printing Page 8
9 Scaffold Fabrication by 3D Thermoplastic Inkjet Printing One of the solid freeform fabrication (SFF) techniques Allows fabrication using any material that can be injected and then formed in situ The process exploits variations in solubility and thermal properties among the build materials Scaffold Fabrication by 3D Thermoplastic Inkjet Printing Removal of the Solid Phase by Solvent Dissolution CAD Design of Scaffolds With Defined Interconnectivity Fabrication of CAD Designed Scaffolds by 3-D Microprinting Injection of Degradable Crosslinkable Macromer in the Scaffold s Solid Phase Page 9
10 Bioprinting Bio-ink: cells in aqueous solution for rheologic properties Bioscaffold (or biopaper ): surface for cell attachment and expression of matrix secretion Hydrogel for controlled delivery of cells & biomolecules 3D Printed Models for Surgical Planning and Intraoperative Guidance Page 10
11 Charcot Arthropathy with Spinopelvic Dissociation 30 year old man with thoracic level paralysis and developmental delay 6 inch diameter ulcer with purulence at lumbosacral junction Poor sitting balance and further ulcer risk based on spinopelvic dissociation Charcot Arthropathy with Spinopelvic Dissociation Page 11
12 POEMS Syndrome POEMS Syndrome Polyneuropathy Organomegaly Endocrinopathy Monoclonal Gammopathy Skin Changes Page 12
13 POEMS Myeloma with Resorption of Skull Base and Upper Cervical Spine POEMS Myeloma with Resorption of Skull Base and Upper Cervical Spine C1 and C2 Foramen Magnum Skull Base Page 13
14 Touch adds to comprehension Three-dimensional printing permits greater understanding of complicated anatomy allowing surgeons to treat complex patients with greater safety & better outcomes. Page 14
15 Patient Counselling: One model is worth a thousand words Teaching Anatomic Pathology: Supplement to cadavers Page 15
16 The Future: Gaps Composite Tissue Regeneration Brain-Computer Interface linked to Tissue & Organ Regeneration Cells and Biomaterials in Single additive Manufacturing Implant The Future: Research Questions What are the pertinent biologic processes at the junctions between different tissue types, and how can we engineer them in 3D? Do we manufacture and implant a 3D tissue or organ, or do we manufacture and implant a bioreactor to induce the formation of the new tissue/organ in vivo? Page 16
17 Tendon and Ligament Tissue Engineering Clinical Needs: Degenerative tendon tears Traumatic tendon and ligament injuries Clinical Issues: Musculotendinous junction Enthesis: tendon/ligament to bone junction Intrasynovial Environment Composite Tissue Regeneration Tendon and Ligament Tissue Engineering Current Treatment Options Direct repair to bone (e.g. rotator cuff repair) Direct repair to muscle (e.g. tendo achilles repair to gastrocsoleus) Substitution (e.g. anterior cruciate ligament reconstruction via bonetendon-bone patellar graft or semitendinosus graft Page 17
18 Tendon and Ligament Tissue Engineering Create scaffolds that resist tensile load Culture fibroblasts on scaffolds Deliver signaling molecules to fibroblasts that have attached to scaffolds Assess engineered tendon or ligament by collagen production and tensile mechanical strength Self-Assembled Block Copolymer Transmission Electron Microscopy Low Magnification High Magnification PCLF-co-PMMA, 82% PCLF Page 18
19 Tendon/Ligament Scaffold SEM Collagen I Production on Fibroblast-Seeded Tendon/Ligament Scaffolds at 4 Weeks in Culture with Platelet Lysate and Fibroblast Growth Factor Page 19
20 Acknowledgements Armed Forces Institute of Regenerative Medicine Page 20
21 Acknowledgements Funding Mayo Foundation National Institutes of Health (R01 AR45871, R01 EB03060, R01 EB02390 Department of Defense Hulman-George Foundation The Team Page 21
22 Page 22
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