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3D printing of bone structure – why does not be done with a hybrid printer

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Worldwide, 2.2 million bone grafts are carried out per year and their huge number indicates a deficit of donor bone [19]. 500.000 bone grafts are carried out per year in the US, and almost half of them are associated with spine fusion [11] or with fractures, tumours and congenital diseases [9]. And Brydone at al. noted that around 4.000.000 operations involving bone grafting and bone substitutes are performed around the world annually [1]. Currently, the «gold standard» for a bone graft is an autograft, as it possesses all the qualities necessary for the growth of a new bone, namely osteoconductivity, osteogenicity and osteoinductivity .

The main complications are associated with the donor location of the bone graft and include arteriovenous fistula, urethral damage, massive blood loss, deep infection, chronic pain and abdominal hernias. An autologous bone graft, obtained from the iliac crest, is taken and is most commonly used in bone reconstructive operations, but it cannot be utilized in pediatric cases. Other complications related to the donor location include: pelvic instability and low back pain, avulsion of the anterior superior iliac spine [7, 8, 20]. The minor complications related to the donor location of the bone graft include problems associated with the wound healing, the formation of a hematoma and cosmetic deformations [4, 10, 12, 18, 30].


The clinical alternative to the autografts are allogeneic bone grafts taken from a bone bank and taken from cadaver-derived bones. Although they are well known and available; their use is associated with an increase in the costs of treatment, the risk of immune rejection in some patients, the possibility of infections transmitted by the donor and a loss of mechanical and biological characteristics possessed by allografts [14,16].

Because of all these complications and risks accompanying the use of allografts, the bone tissue engineering aims to develop methods for synthesizing and/or regeneration of the bone, which will restore or improve its function in vivo [22].

3D printing (3DP) – a technology developed in the early 90`s at the Technology Institute of Massachusetts (Cambridge, MA) by Sachs at al. — is used in the bone tissue engineering and allows the direct production of such bone scaffolds with a porous structure of CAD files [27].

A scaffold for bone regeneration must meet the following conditions:

  1. To have an appropriate extracellular matrix structure providing reliable cell adhesion, proliferation and differentiation;
  2. To have an architecture identical to the bone tissue which has to be made of biodegradable or biocompatible material;
  3. To have an internal design providing high mechanical strength to support various loads [5, 26].

The bone is a complex biological composite material comprised of collagen fibrils organization, in which the crystals of hydroxyapatite — Cа10 (РО4)6 (ОН)2 are embedded. The aim of developing a scaffold of calcium phosphate through 3D printing is achievable. Technologically, it should be achieved by spraying of organic or inorganic binders on a horizontally layer of calcium phosphate. The size and the distribution of the particles in the powder used for printing determine the micro porosity and the resolution of the printed material [2]. For the development of a calcium phosphate scaffold, porous hydroxyapatite granules corresponding to a size of 22 μm are used and cubic voxel size of 240 μm corresponding to a resolution of 106 dpi were achieved and the cavities in the printed scaffold have a minimum size of 100 μm [22]. The average particle size of a calcium phosphate in a study of Butscher has been 21.20 ± 0.09 μm [3]. In a study of Inzana at al., the particles’ sizes have been from 30 μm to 70 μm and the measured porosity of the printed scaffold from 20 μm to 50 μm [15]. The method, using a powder of calcium phosphate of 3D printing could be used in developing the structures resembling compact bone and the in vivo experiments conducted by Inzana at al. [15] indicate good osteoconductivety, but because it is not possible to control the pore size and to achieve the thickness of the trabeculae between 145 μm and 192 μm, as observed in human trabecular bone, an identical structure to human trabecular bone could not be created by this method [21].

Laser technologies allow the creation of mimetic scaffolds with greater precision and reproducibility. Two-photon polymerization (fig.1) allows the production of 3D microstructures with a complex architecture and precise dimensions [24, 25].  This process uses the simultaneous absorption of two photons of infrared (780 nm) or green (515 nm) laser light which takes place at high laser intensity within a spatially localized focus region. The microstructures produced by 2PP-production are precise models of the relevant computer-generated designs and show in vitro good cell adhesion and proliferation [17].  According to Sikavitsas et al., the controlling of the function of the bone cells in vivo can be achieved by designing the scaffold with mechanical characteristics that permit osteoinductive fluid flow in the scaffold [28]. This design is possible by associating the three-dimensional image diagnosis, fluid flow modeling and the numerical simulation of the scaffold physical properties.


According to Professor Guldberg structures of platforms constructed from biometeriali, must often be modified or combined with bioactive components, to achieve the desired properties. [13]

The creation of a new hybrid 3D printer – through the combination of two technologies – jet 3D printing and two-photon polymerization can help in creating of new hybrid bone implant that would replace the use of autografts and allografts.


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  2. Butscher A, Powder based three-dimensional printing of calcium phosphate structures for scaffold engineering, ETH No. 21210; 2013
  3. Butscher A, Bohner M, Roth C, Ernstberger A, Heuberger R, Doebelin N, et al. Printability of calcium phosphate powders for three-dimensional printing of tissue engineering scaffolds. Acta 2012; 8(1):373–385.
  4. Catinella FP, De Laria GA, DeWald RL: Falseaneurysm of the superior gluteal artery- a complication of iliiac crest bone grafting. Spine 15: 1360-1362,1990.
  5. Cheah CM, Chua CK, Leong KF, Chua SW. Development of a tissue engineering scaffold structure library for rapid prototyping. Part 1: lnvestigation and classification. Int J Adv Manuf Technol 2003;21:291-301
  6. Chichkov B. Two-photon полимеризатион енханцес rapid prototyping оф медицал devices. SPIE—The International Society for Optical Engineering, 2007
  7. Cohn BT, Krackow KA: Fracture of the iliac crest following bone grafting-A case report. Orthopedics 11:473-474, 1988.
  8. Coventry MB, Tapper EM: Pelvic instability-A consequence of removing iliac bone for grafting. JBone Joint Surg 54A:83-101, 1972
  9. Dias AG, Lopes MA, Santos JD, Afonso A, Tsuru K, Osaka A, Hayakawa S, Takashima S, Kurabayashi Y. In vivo performance of biodegradable calcium phosphate glass ceramics using the rabbit model: histological and SEM observation. J Biomater ApplJan;20(3):253-66; 2006
  10. Escales F, DeWald RL: Combined traumatic arteriovenous fistula and ureteral iniurv: A complication of bone grafting. J Bone»J4nt Surg’59A:270-271.1977
  11. Greenwald AS, Boden SD, Goldberg VM, Khan Y, Laurencin CT, Rosier RN; American Academy of Orthopaedic Surgeons. The Committee on Biological Implants. Bone-graft substitutes: facts, fictions, and applications. J Bone Joint Surg Am. 2001;83-A Suppl 2 Pt 2:98-103.
  12. Hamad MM, Majeed SA: Incisional hernia through iliac crest defects. Arch Orthop Trauma Surg Heppenstall RB: Bone Grafting in Fracture Treatment and Healing. Philadelphia, WB Saunders 1980
  13. Healy KE, Guldberg RE Bone tissue engineering J Musculoskelet Neuronal Interact 7(4):328-330; 2007
  14. Ikada Y. Tissue Engineering Elsevier Ltd.,p.121; 2006
  15. Inzana JA, Olveraa D, Fullerd SM, Kellyd JP, Graeved OA, Schwarza EM, Katesa SL, Awada HA. 3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration Biomaterials. April; 35(13): 4026–4034. 2014
  16. Kakar S, Einhorn TA Tissue Engineering of Bone.p278; CRC Press, 2005
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  18. Kurz LT, Garfin SR, Booth RE: Harvesting autogenous iliac bone graft: A review of complication and Spine 14: 1324-133 1, 1989.
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  20. Laurie SWS, Kaban LB, Mulliken JB, Murray JE: Donor-site morbidity after harvesting rib and iliac bone. J Plast Reconstr Surg 73:933-938, 1984
  21. Minkov DM, Rossmanov VB, De Clerck N, De Schutter T, Georgiev G. Micro-computer tomography and bilateral ultrasound osteometry of patient subject of total hip artheoplasty JBMR, Vol2-2; 2008
  22. Müller B, Deyhle H,. Fierz FC, Irsen SH, Yoon J Y, Mushkolaj S, Boss O, Vorndran E, Gbureck U, Degistirici Ö, Biomimetics and Bioinspiration, Vol. 7401, 2009
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  25. Raimondi MT, Eaton SM, Nava MM, Laganà M, Cerullo G, et al. Two-photon laser polymerization: from fundamentals to biomedical application in tissue engineering and regenerative medicine. J Appl Biomater Biomech 10: 55–65; 2012
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Figure 1. Schematic of the experimental setup used for two photon polymerization (2PP) processing [6].

3D printing of bone structure – why does not be done with a hybrid printer
Written by: Dimitar Minkov Minkov
Published by: Басаранович Екатерина
Date Published: 12/15/2016
Edition: euroasia-science_6(27)_23.06.2016
Available in: Ebook

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