Skip to main content
SpringerLink
Log in

Design Control for Clinical Translation of 3D Printed Modular Scaffolds

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9

Similar content being viewed by others

References

  1. Arthur, W. B. The Nature of Technology: What it is and How it Evolves. New York: Free Press, 2009.

    Google Scholar 

  2. Class II Special Controls Guidance Document: Intervertebral Body Fusion Device. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071408.htm. 2007.

  3. Coelho, P. G., P. R. Fernandes, H. C. Rodrigues, J. B. Cardoso, and J. M. Guedes. Numerical modeling of bone tissue adaptation—a hierarchical approach for bone apparent density and trabecular structure. J. Biomech. 42:830–837, 2009.

    Article  CAS  PubMed  Google Scholar 

  4. Coelho, P. G., P. R. Fernandes, and H. C. Rodrigues. Multiscale modeling of bone tissue with surface and permeability control. J. Biomech. 44:321–329, 2011.

    Article  Google Scholar 

  5. Crawford, D. C., T. M. DeBerardino, and R. J. Williams, 3rd. NeoCart, an autologous cartilage tissue implant, compared with microfracture for treatment of distal femoral cartilage lesions: an FDA phase-II prospective, randomized clinical trial after two years. J. Bone Joint Surg. Am. 94:979–989, 2012.

    PubMed  Google Scholar 

  6. Design Control Guidance for Medical Device Manufacturers, http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm070627.htm.

  7. Dias, M. R., J. M. Guedes, C. L. Flanagan, S. J. Hollister, and P. R. Fernandes. Optimization of scaffold design for bone tissue engineering: a computational and experimental study. Med. Eng. Phys. 36:448–457, 2014.

    Article  PubMed  Google Scholar 

  8. Doyle, H., S. Lohfield, and P. McHugh. Predicting the elastic properties of selective laser sintered PCL/beta-TCP bone scaffold materials using computational modeling. Ann. Biomed. Eng. 42:661–677, 2014.

    Article  PubMed  Google Scholar 

  9. Eosoly, S., N. E. Vrana, S. Lohfeld, M. Hindie, and L. Looney. Interaction of cell culture with composition effects on the mechanical properties of polycaprolactone-hydroxyapatite scaffolds fabricated via selected laser sintering (SLS). Mater. Sci. Eng. C 32:2250–2257, 2012.

    Article  CAS  Google Scholar 

  10. Eshraghi, S., and S. Das. Mechanical and microstructural properties of polycaprolactone scaffolds with one-dimensional, two-dimensional, and three-dimensional orthogonally oriented porous architectures produced by selective laser sintering. Acta Biomater. 6:2467–2476, 2010.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Eshraghi, S., and S. Das. Micromechanical finite-element modeling and experimental characterization of the compressive mechanical properties of polycaprolactone-hydroxyapatite composite scaffolds prepared by selective laser sintering for bone tissue engineering. Acta Biomater. 8:3138–3143, 2012.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Harrison, R. H., J. P. St-Pierre, and M. M. Stevens. Tissue engineering and regenerative medicine: a year in review. Tissue Eng. Part B 20:1–16, 2014.

    Article  Google Scholar 

  13. Hollister, S. J. Porous scaffold design for tissue engineering. Nat. Mater. 4:518–524, 2005.

    Article  CAS  PubMed  Google Scholar 

  14. Hollister, S. J., and W. L. Murphy. Scaffold translation: barriers between concept and clinic. Tissue Eng. Part B 17:459–474, 2011.

    Article  Google Scholar 

  15. Hollister, S. J., R. A. Levy, T. M. Chu, J. W. Halloran, and S. E. Feinberg. An image-based approach for designing and manufacturing craniofacial scaffolds. Int. J. Oral Maxillofac. Surg. 29:67–71, 2000.

    Article  CAS  PubMed  Google Scholar 

  16. Hu, W. W., Y. Elkasabi, H. Y. Chen, Y. Zhang, J. Lahann, S. J. Hollister, and P. H. Krebsbach. The use of reactive polymer coatings to facilitate gene delivery from poly (epsilon-caprolactone) scaffolds. Biomaterials 30:5785–5792, 2009.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Jungebluth, P., E. Alici, S. Baiguera, K. Le Blanc, P. Blomberg, B. Bozoky, C. Crowley, O. Einarsson, K. H. Grinnemo, T. Gudbjartsson, S. Le Guyader, G. Henriksson, O. Hermanson, J. E. Juto, B. Leidner, T. Lilja, J. Liska, T. Luedde, V. Lundin, G. Moll, B. Nilsson, C. Roderburg, S. Stromblad, T. Sutlu, A. I. Teixeira, E. Watz, A. Seifalian, and P. Macchiarini. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 378:1997–2004, 2011.

    Article  CAS  PubMed  Google Scholar 

  18. Kandziora, F., G. Schollmeier, M. Scholz, J. Schaefer, A. Scholz, G. Schmidmaier, R. Schroder, H. Bail, G. Duda, T. Mittlmeier, and N. P. Hass. Influence of cage design on interbody fusion in a sheep cervical spine model. J. Neurosurg. 96:321–332, 2002.

    PubMed  Google Scholar 

  19. Kang, H., C. Y. Lin, and S. J. Hollister. Topology optimization of three dimensional tissue engineering scaffold architectures for prescribed bulk modulus and diffusivity. Str. Multidiscipl. Optim. 42:633–644, 2010.

    Article  Google Scholar 

  20. Kang, H., S. J. Hollister, F. La Marca, P. Park, and C. Y. Lin. Porous biodegradable lumbar interbody fusion cage design and fabrication using integrated global-local topology optimization with laser sintering. J. Biomech. Eng. 135:101013–101018, 2013.

    Article  PubMed  Google Scholar 

  21. Kinsel, D. Design control requirements for medical device development. World J. Pediatr. Congenit. Heart Surg. 3:77–81, 2012.

    Article  PubMed  Google Scholar 

  22. Lin, C. Y., N. Kikuchi, and S. J. Hollister. A novel method for biomaterial scaffold internal architecture design to match bone elastic properties with desired porosity. J. Biomech. 37:623–636, 2004.

    Article  PubMed  Google Scholar 

  23. Low, S. W., Y. J. Ng, T. T. Yeo, and N. Chou. Use of Osteoplug polycaprolactone implants as novel burr-hole covers. Singapore Med. J. 50:777–780, 2009.

    CAS  PubMed  Google Scholar 

  24. May-Newman, K., and G. B. Cornwall. Teaching medical device design using design control. Expert Rev. Med. Devices 9:7–14, 2012.

    Article  PubMed  Google Scholar 

  25. Murgu, S., and H. Colt. Tracheobronchomalacia and excessive dynamic airway collapse. Clin. Chest Med. 34:527–555, 2013.

    Article  PubMed  Google Scholar 

  26. Partee, B., S. J. Hollister, and S. Das. Selective laser sintering process optimization for layered manufacturing of CAPA 6501 polycaprolactone bone tissue engineering scaffolds. ASME J. Manuf. Sci. Eng. 128:531–540, 2006.

    Article  Google Scholar 

  27. Saito, E., D. Suarez-Gonzalez, R. R. Rao, J. P. Stegemann, W. L. Murphy, and S. J. Hollister. Use of micro-computed tomography to nondestructively characterize biomineral coatings on solid freeform fabricated poly (l-lactic acid) and poly (epsilon-caprolactone) scaffolds in vitro and in vivo. Tissue Eng. Part C 19:507–517, 2013.

    Article  CAS  Google Scholar 

  28. Schantz, J. T., T. C. Lim, C. Ning, S. H. Teoh, K. C. Tan, S. C. Wang, and D. W. Hutmacher. Cranioplasty after trephination using a novel biodegradable burr hole cover: technical case report. Neurosurgery 58:ONS-E176, 2006; discussion ONS-E176.

  29. Schwartz, S. D., J. P. Hubschman, G. Heilwell, V. Franco-Cardenas, C. K. Pan, R. M. Ostrick, E. Mickunas, R. Gay, I. Klimanskaya, and R. Lanza. Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379:713–720, 2012.

    Article  CAS  PubMed  Google Scholar 

  30. Smith, M. H., C. L. Flanagan, J. M. Kemppainen, J. A. Sack, H. Chung, S. Das, S. J. Hollister, and S. E. Feinberg. Computed tomography-based tissue-engineered scaffolds in craniomaxillofacial surgery. Int. J. Med. Robot. 3:207–216, 2007.

    Article  CAS  PubMed  Google Scholar 

  31. Teixeira, M. B., and R. Bradley. Design Controls for the Medical Device Industry. New York: Marcel Dekker Inc, 2003.

    Google Scholar 

  32. Updated 510(k) Sterility Review Guidance K90-1; Final Guidance for Industry and FDA. http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm072783.htm.

  33. Williams, J. M., A. Adewunmi, R. M. Schek, C. L. Flanagan, P. H. Krebsbach, S. E. Feinberg, S. J. Hollister, and S. Das. Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. Biomaterials 26:4817–4827, 2005.

    Article  CAS  PubMed  Google Scholar 

  34. Yoo, D. J. Porous scaffold design using the distance field and triply periodic minimal surface models. Biomaterials 32:7741–7754, 2011.

    Article  CAS  PubMed  Google Scholar 

  35. Zopf, D. A., S. J. Hollister, M. E. Nelson, R. G. Ohye, and G. E. Green. Bioresorbable airway splint created with a three-dimensional printer. N. Engl. J. Med. 368:2043–2045, 2013.

    Article  CAS  PubMed  Google Scholar 

  36. Zopf, D. A., C. L. Flanagan, M. Wheeler, S. J. Hollister, and G. E. Green. Treatment of severe porcine tracheomalacia with a 3-dimensionally printed, bioresorbable, external airway splint. JAMA Otolaryngol. Head Neck Surg. 140:66–71, 2014.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the financial support of the NIH, R21 HD076370 (to S.J.H., G.E.G. and M.B.W.) for the tracheal splint work and NIH R01 AR 060892 (to S.J.H., M.B.W., E.E. and S.N.S.) for the cervical spine fusion work. In addition, some BMP2 delivery work was supported by NIH R21 DE0224439 (to S.J.H. and M.B.W). We gratefully acknowledge the contributions of Chanaka Rabel, PhD, Department of Animal Sciences, University of Illinois, Urbana-Champaign, Aaron Maki, PhD, Department of Bioengineering, University of Illinois, Urbana-Champaign, Jamey Cooper, University of Illinois, Urbana-Champaign, Anna Ercolin, DVM, Department of Animal Sciences, University of Illinois, Urbana-Champaign, and Kelly Roballo, Department of Animal Sciences, University of Illinois, Urbana-Champaign, for collection of the postsurgical respiratory data and animal monitoring for the tracheal splint; and especially Jonathan F. Mosley, Department of Animal Sciences, University of Illinois, Urbana-Champaign, along with his staff at the Physiology Research Laboratory/Imported Swine Research Laboratory, for the animal management, surgery assistance, and excellent animal care for the tracheal splint and cervical spine fusion work. Finally, we acknowledge the work of Sean L. Borkowski and Ashleen R. Knutsen on the dynamic fatigue testing of the cervical spine cages.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, The University of Michigan, Rm 2214 Lurie Biomedical Engineering Bldg, 1101 Beal Ave, Ann Arbor, MI, USA

    Scott J. Hollister, Colleen L. Flanagan & Janki J. Patel

  2. Department of Mechanical Engineering, The University of Michigan, Ann Arbor, MI, USA

    Scott J. Hollister

  3. Department of Surgery, The University of Michigan, Ann Arbor, MI, USA

    Scott J. Hollister

  4. Division of Pediatric Otolaryngology, Department of Otolaryngology – Head and Neck Surgery, The University of Michigan, Ann Arbor, MI, USA

    David A. Zopf, Robert J. Morrison, Hassan Nasser & Glenn E. Green

  5. J. Vernon Luck, Sr., M.D. Orthopaedic Research Center at the Orthopaedic Institute for Children, Los Angeles, USA

    Edward Ebramzadeh & Sophia N. Sangiorgio

  6. Department of Orthopaedic Surgery, University of California, Los Angeles, USA

    Edward Ebramzadeh & Sophia N. Sangiorgio

  7. Institute for Genomic Biology and Department of Animal Sciences, The University of Illinois, Urbana-Champaign, Champaign, USA

    Matthew B. Wheeler

Authors
  1. Scott J. Hollister
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Colleen L. Flanagan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David A. Zopf
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert J. Morrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hassan Nasser
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Janki J. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Edward Ebramzadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sophia N. Sangiorgio
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Matthew B. Wheeler
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Glenn E. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott J. Hollister.

Additional information

Associate Editor Nadya Lumelsky oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hollister, S.J., Flanagan, C.L., Zopf, D.A. et al. Design Control for Clinical Translation of 3D Printed Modular Scaffolds. Ann Biomed Eng 43, 774–786 (2015). https://doi.org/10.1007/s10439-015-1270-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-015-1270-2

Keywords

Search

Navigation