Hostname: page-component-6bf8c574d5-2jptb Total loading time: 0 Render date: 2025-02-18T20:21:13.546Z Has data issue: false hasContentIssue false
  • English
  • Français

3D printing of poly(ε-caprolactone)/poly(D,L-lactide-co-glycolide)/hydroxyapatite composite constructs for bone tissue engineering

Published online by Cambridge University Press:  27 June 2018

Kazim K. Moncal ,
Dong N. Heo ,
Kevin P. Godzik ,
Donna M. Sosnoski ,
Oliver D. Mrowczynski ,
Elias Rizk ,
Veli Ozbolat ,
Scott M. Tucker ,
Ethan M. Gerhard  and
Madhuri Dey
...Show all authors
Kazim K. Moncal
Affiliation:
Engineering Science and Mechanics, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Dong N. Heo
Affiliation:
Engineering Science and Mechanics, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Kevin P. Godzik
Affiliation:
Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Donna M. Sosnoski
Affiliation:
Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Oliver D. Mrowczynski
Affiliation:
Department of Neurosurgery, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania 17033, USA
Elias Rizk
Affiliation:
Department of Neurosurgery, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania 17033, USA
Veli Ozbolat
Affiliation:
Engineering Science and Mechanics, Pennsylvania State University, University Park, Pennsylvania 16802, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Department of Mechanical Engineering, Ceyhan Engineering Faculty, Cukurova University, Adana 01330, Turkey
Scott M. Tucker
Affiliation:
Engineering Science and Mechanics, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Department of Orthopaedics and Rehabilitation, College of Medicine, Pennsylvania State University, Hershey 17033, Pennsylvania, USA
Ethan M. Gerhard
Affiliation:
Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Madhuri Dey
Affiliation:
Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Gregory S. Lewis
Affiliation:
Engineering Science and Mechanics, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Department of Orthopaedics and Rehabilitation, College of Medicine, Pennsylvania State University, Hershey 17033, Pennsylvania, USA
Jian Yang
Affiliation:
Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA; and Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Ibrahim T. Ozbolat*
Affiliation:
Engineering Science and Mechanics, Pennsylvania State University, University Park, Pennsylvania 16802, USA; Huck Institutes of the Life Sciences, Pennsylvania State University, University Park 16802, Pennsylvania, USA; Biomedical Engineering, Pennsylvania State University, University Park 16802, Pennsylvania, USA; and Materials Research Institute, Pennsylvania State University, University Park 16802, Pennsylvania, USA
*
a)Address all correspondence to this author. e-mail: ito1@psu.edu
Get access

Abstract

Three-dimensional (3D) printing technology is a promising method for bone tissue engineering applications. For enhanced bone regeneration, it is important to have printable ink materials with appealing properties such as construct interconnectivity, mechanical strength, controlled degradation rates, and the presence of bioactive materials. In this respect, we develop a composite ink composed of polycaprolactone (PCL), poly(D,L-lactide-co-glycolide) (PLGA), and hydroxyapatite particles (HAps) and 3D print it into porous constructs. In vitro study revealed that composite constructs had higher mechanical properties, surface roughness, quicker degradation profile, and cellular behaviors compared to PCL counterparts. Furthermore, in vivo results showed that 3D-printed composite constructs had a positive influence on bone regeneration due to the presence of newly formed mineralized bone tissue and blood vessel formation. Therefore, 3D printable ink made of PCL/PLGA/HAp can be a highly useful material for 3D printing of bone tissue constructs.

Keywords

3D printingcomposite inkbone tissue regenerationcalvarial defects
Type
Invited Article
Information
Journal of Materials Research , Volume 33 , Issue 14: Focus Issue: 3D Printing of Biomaterials , 27 July 2018 , pp. 1972 - 1986
Copyright
Copyright © Materials Research Society 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Tang, D., Tare, R.S., Yang, L.Y., Williams, D.F., Ou, K.L., and Oreffo, R.O.: Biofabrication of bone tissue: Approaches, challenges and translation for bone regeneration. Biomaterials 83, 363–382 (2016).CrossRefGoogle ScholarPubMed
Venkatesan, J., Bhatnagar, I., Manivasagan, P., Kang, K.H., and Kim, S.K.: Alginate composites for bone tissue engineering: A review. Int. J. Biol. Macromol. 72, 269–281 (2015).CrossRefGoogle ScholarPubMed
Gao, C., Deng, Y., Feng, P., Mao, Z., Li, P., Yang, B., Deng, J., Cao, Y., Shuai, C., and Peng, S.: Current progress in bioactive ceramic scaffolds for bone repair and regeneration. Int. J. Mol. Sci. 15, 4714–4732 (2014).CrossRefGoogle ScholarPubMed
Mediero, A., Wilder, T., Perez-Aso, M., and Cronstein, B.N.: Direct or indirect stimulation of adenosine A2A receptors enhances bone regeneration as well as bone morphogenetic protein-2. FASEB J. 29, 1577–1590 (2015).CrossRefGoogle ScholarPubMed
Semyari, H., Rajipour, M., Sabetkish, S., Sabetkish, N., Abbas, F.M., and Kajbafzadeh, A.M.: Evaluating the bone regeneration in calvarial defect using osteoblasts differentiated from adipose-derived mesenchymal stem cells on three different scaffolds: An animal study. Cell Tissue Banking 17, 69–83 (2016).CrossRefGoogle Scholar
Shadjou, N. and Hasanzadeh, M.: Silica-based mesoporous nanobiomaterials as promoter of bone regeneration process. J. Biomed. Mater. Res., Part A 103, 3703–3716 (2015).CrossRefGoogle ScholarPubMed
Kim, J., McBride, S., Donovan, A., Darr, A., Magno, M.H.R., and Hollinger, J.O.: Tyrosine-derived polycarbonate scaffolds for bone regeneration in a rabbit radius critical-size defect model. Biomed. Mater. 10, 035001 (2015).CrossRefGoogle Scholar
Shi, S., Jiang, W.B., Zhao, T.X., Aifantis, K.E., Wang, H., Lin, L., Fan, Y.B., Feng, Q.L., Cui, F.Z., and Li, X.M.: The application of nanomaterials in controlled drug delivery for bone regeneration. J. Biomed. Mater. Res., Part A 103, 3978–3992 (2015).CrossRefGoogle ScholarPubMed
Heller, M., Bauer, H.K., Goetze, E., Gielisch, M., Ozbolat, I.T., Moncal, K.K., Rizk, E., Seitz, H., Gelinsky, M., Schroder, H.C., Wang, X.H., Muller, W.E., and Al-Nawas, B.: Materials and scaffolds in medical 3D printing and bioprinting in the context of bone regeneration. Int. J. Comput. Dent. 19, 301–321 (2016).Google ScholarPubMed
Vural, A.C., Odabas, S., Korkusuz, P., Saglam, A.S.Y., Bilgic, E., Cavusoglu, T., Piskin, E., and Vargel, I.: Cranial bone regeneration via BMP-2 encoding mesenchymal stem cells. Artif. Cells, Nanomed., Biotechnol. 45, 544–550 (2017).CrossRefGoogle ScholarPubMed
van der Stok, J., Lozano, D., Chai, Y.C., Yavari, S.A., Coral, A.P.B., Verhaar, J.A.N., Gomez-Barrena, E., Schrooten, J., Jahr, H., Zadpoor, A.A., Esbrit, P., and Weinans, H.: Osteostatin-coated porous titanium can improve early bone regeneration of cortical bone defects in rats. Tissue Eng., Part A 21, 1495–1506 (2015).CrossRefGoogle ScholarPubMed
Ni, P., Ding, Q.X., Fan, M., Liao, J.F., Qian, Z.Y., Luo, J.C., Li, X.Q., Luo, F., Yang, Z.M., and Wei, Y.Q.: Injectable thermosensitive PEG–PCL–PEG hydrogel/acellular bone matrix composite for bone regeneration in cranial defects. Biomaterials 35, 236–248 (2014).CrossRefGoogle ScholarPubMed
Gredes, T., Kunath, F., Gedrange, T., and Kunert-Keil, C.: Bone regeneration after treatment with covering materials composed of flax fibers and biodegradable plastics: A histological study in rats. BioMed Res. Int. 5146285 (2016).Google ScholarPubMed
Cox, S.C., Thornby, J.A., Gibbons, G.J., Williams, M.A., and Mallick, K.K.: 3D printing of porous hydroxyapatite scaffolds intended for use in bone tissue engineering applications. Mater. Sci. Eng., C 47, 237–247 (2015).CrossRefGoogle ScholarPubMed
Kao, C.T., Lin, C.C., Chen, Y.W., Yeh, C.H., Fang, H.Y., and Shie, M.Y.: Poly(dopamine) coating of 3D printed poly(lactic acid) scaffolds for bone tissue engineering. Mater. Sci. Eng., C 56, 165–173 (2015).CrossRefGoogle ScholarPubMed
Holmes, B., Bulusu, K., Plesniak, M., and Zhang, L.G.: A synergistic approach to the design, fabrication and evaluation of 3D printed micro and nano featured scaffolds for vascularized bone tissue repair. Nanotechnology 27, 064001 (2016).CrossRefGoogle ScholarPubMed
Wang, M.O., Vorwald, C.E., Dreher, M.L., Mott, E.J., Cheng, M.H., Cinar, A., Mehdizadeh, H., Somo, S., Dean, D., Brey, E.M., and Fisher, J.P.: Evaluating 3D-printed biomaterials as scaffolds for vascularized bone tissue engineering. Adv. Mater. 27, 138–144 (2015).CrossRefGoogle ScholarPubMed
Lee, S.J., Lee, D., Yoon, T.R., Kim, H.K., Jo, H.H., Park, J.S., Lee, J.H., Kim, W.D., Kwon, I.K., and Park, S.A.: Surface modification of 3D-printed porous scaffolds via mussel-inspired polydopamine and effective immobilization of rhBMP-2 to promote osteogenic differentiation for bone tissue engineering. Acta Biomater. 40, 182–191 (2016).CrossRefGoogle ScholarPubMed
Pati, F., Song, T.H., Rijal, G., Jang, J., Kim, S.W., and Cho, D.W.: Ornamenting 3D printed scaffolds with cell-laid extracellular matrix for bone tissue regeneration. Biomaterials 37, 230–241 (2015).CrossRefGoogle ScholarPubMed
Bose, S., Vahabzadeh, S., and Bandyopadhyay, A.: Bone tissue engineering using 3D printing. Mater. Today 16, 496–504 (2013).CrossRefGoogle Scholar
Hospodiuk, M., Moncal, K.K., Dey, M., and Ozbolat, I.T.: Extrusion-based biofabrication in tissue engineering and regenerative medicine. In: 3D Printing and Biofabrication, Ovsianikov, A., Yoo, J., Mironov, V. eds. (Springer International Publishing, 2016); pp. 1–27.Google Scholar
Tsang, V.L. and Bhatia, S.N.: Three-dimensional tissue fabrication. Adv. Drug Delivery Rev. 56, 1635–1647 (2004).CrossRefGoogle ScholarPubMed
Heo, S.J., Kim, S.E., Wei, J., Kim, D.H., Hyun, Y.T., Yun, H.S., Kim, H.K., Yoon, T.R., Kim, S.H., Park, S.A., Shin, J.W., and Shin, J.W.: In vitro and animal study of novel nano-hydroxyapatite/poly(epsilon-caprolactone) composite scaffolds fabricated by layer manufacturing process. Tissue Eng., Part A 15, 977–989 (2009).CrossRefGoogle Scholar
Ulery, B.D., Nair, L.S., and Laurencin, C.T.: Biomedical applications of biodegradable polymers. J. Polym. Sci., Part B: Polym. Phys. 49, 832–864 (2011).CrossRefGoogle ScholarPubMed
Kwon, D.Y., Kwon, J.S., Park, S.H., Park, J.H., Jang, S.H., Yin, X.Y., Yun, J.H., Kim, J.H., Min, B.H., Lee, J.H., Kim, W.D., and Kim, M.S.: A computer-designed scaffold for bone regeneration within cranial defect using human dental pulp stem cells. Sci. Rep. 5, 12721 (2015).CrossRefGoogle ScholarPubMed
Lee, J.B., Kim, S.E., Heo, D.N., Kwon, I.K., and Choi, B.J.: In vitro characterization of nanofibrous PLGA/gelatin/hydroxyapatite composite for bone tissue engineering. Macromol. Res. 18, 1195–1202 (2010).CrossRefGoogle Scholar
Wei, G.B. and Ma, P.X.: Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering. Biomaterials 25, 4749–4757 (2004).CrossRefGoogle ScholarPubMed
Li, X., Zhang, S., Zhang, X., Xie, S., Zhao, G., and Zhang, L.: Biocompatibility and physicochemical characteristics of poly(ε-caprolactone)/poly(lactide-co-glycolide)/nano-hydroxyapatite composite scaffolds for bone tissue engineering. Mater. Des. 114, 149–160 (2017).CrossRefGoogle Scholar
Ozbolat, I.T., Chen, H., and Yu, Y.: Development of ‘Multi-arm Bioprinter’ for hybrid biofabrication of tissue engineering constructs. Robot. Comput. Integrated Manuf. 30, 295–304 (2014).CrossRefGoogle Scholar
Ozbolat, V., Dey, M., Ayan, B., Povilianskas, A., Demirel, M.C., and Ozbolat, I.T.: 3D printing of PDMS improves its mechanical and cell adhesion properties. ACS Biomater. Sci. Eng. 4, 682–693 (2018).CrossRefGoogle Scholar
Yang, J., Webb, A.R., Pickerill, S.J., Hageman, G., and Ameer, G.A.: Synthesis and evaluation of poly(diol citrate) biodegradable elastomers. Biomaterials 27, 1889–1898 (2006).CrossRefGoogle ScholarPubMed
Zhang, L. and Chan, C.: Isolation and enrichment of rat mesenchymal stem cells (MSCs) and separation of single-colony derived MSCs. J. Visualized Exp. 37, e1852 (2010).Google Scholar
Abderrahim, B., Abderrahman, E., Mohamed, A., Fatima, T., Abdesselam, T., and Krim, O.: Kinetic thermal degradation of cellulose, polybutylene succinate and a green composite: Comparative study. World J. Environ. Eng. 3, 95–110 (2015).Google Scholar
Zhang, J., Liu, Y., Luo, R.F., Chen, S., Li, X., Yuan, S.H., Wang, J., and Huang, N.: In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings. Appl. Surf. Sci. 328, 154–162 (2015).CrossRefGoogle Scholar
Berzina-Cimdina, L. and Borodajenko, N.: Research of calcium phosphates using Fourier transform infrared spectroscopy. Infrared Spectrosc.: Mater. Sci., Eng. Technol. (InTech, 2012); pp. 123–148.Google Scholar
Rhodes, G.: Crystallography Made Crystal Clear: A Guide for Users of Macromolecular Models, 3rd ed. (Elsevier, 2010); pp. 61–306.Google Scholar
Mu, L. and Feng, S.S.: A novel controlled release formulation for the anticancer drug paclitaxel (taxol (R)): PLGA nanoparticles containing vitamin E TPGS. J. Controlled Release 86, 33–48 (2013).CrossRefGoogle Scholar
Velasco, M.A., Narvaez-Tovar, C.A., and Garzon-Alvarado, D.A.: Design, materials, and mechanobiology of biodegradable scaffolds for bone tissue engineering. BioMed Res. Int. 729076 (2015).Google ScholarPubMed
Ozbolat, I.T. and Hospodiuk, M.: Current advances and future perspectives in extrusion-based bioprinting. Biomaterials 76, 321–343 (2016).CrossRefGoogle ScholarPubMed
Ozbolat, I.T., Moncal, K.K., and Gudapati, H.: Evaluation of bioprinter technologies. Addit. Manuf. 13, 179–200 (2017).CrossRefGoogle Scholar
Hospodiuk, M., Dey, M., Sosnoski, D., and Ozbolat, I.T.: The bioink: A comprehensieve review on bioprintable materials. Biotechnol. Adv. 35, 217–239 (2017).CrossRefGoogle ScholarPubMed
Sung, H.J., Meredith, C., Johnson, C., and Galis, Z.S.: The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. Biomaterials 25, 5735–5742 (2004).CrossRefGoogle ScholarPubMed
Hiep, N.T., Chan Khon, H., Hai, N.D., Byong-Taek, L., Toi, V.V., and Hung, L.T.: Biocompatibility of PCL/PLGA-BCP porous scaffold for bone tissue engineering applications. J. Biomater. Sci., Polym. Ed. 28, 864–878 (2017).CrossRefGoogle Scholar
Jones, A.C., Arns, C.H., Sheppard, A.P., Hutmacher, D.W., Milthorpe, B.K., and Knackstedt, M.A.: Assessment of bone ingrowth into porous biomaterials using MICRO-CT. Biomaterials 28, 2491–2504 (2007).CrossRefGoogle ScholarPubMed
D’Mello, S., Atluri, K., Geary, S.M., Hong, L., Elangovan, S., and Salem, A.K.: Bone regeneration using gene-activated matrices. AAPS J. 19, 43–53 (2017).CrossRefGoogle ScholarPubMed
Heo, D.N., Castro, N.J., Lee, S.J., Noh, H., Zhu, W., and Zhang, L.G.: Enhanced bone tissue regeneration using a 3D printed microstructure incorporated with a hybrid nano hydrogel. Nanoscale 9, 5055–5062 (2017).CrossRefGoogle ScholarPubMed
Leberfinger, A.N., Moncal, K.K., Ravnic, D.J., and Ozbolat, I.T.: 3D printing for cell therapy applications. In: Cell Therapy, Emerich, D., Orive, G. eds. (Humana Press, Cham, 2017); pp. 227–248.CrossRefGoogle Scholar
Hung, B.P., Naved, B.A., Nyberg, E.L., Dias, M., Holmes, C.A., Elisseeff, J.H., Dorafshar, A.H., and Grayson, W.L.: Three-dimensional printing of bone extracellular matrix for craniofacial regeneration. ACS Biomater. Sci. Eng. 2, 1806–1816 (2016).CrossRefGoogle ScholarPubMed
Dong, L., Wang, S.J., Zhao, X.R., Zhu, Y.F., and Yu, J.K.: 3D-printed poly(epsilon-caprolactone) scaffold integrated with cell-laden chitosan hydrogels for bone tissue engineering. Sci. Rep. 7, 13412 (2017).CrossRefGoogle ScholarPubMed
Datta, P., Ozbolat, V., Ayan, B., Dhawan, A., and Ozbolat, I.T.: Bone tissue bioprinting for craniofacial reconstruction. Biotechnol. Bioeng. 114, 2424–2431 (2017).CrossRefGoogle ScholarPubMed
Ozbolat, I.T., Peng, W., and Ozbolat, V.: Application areas of 3D bioprinting. Drug Discovery Today 21, 1257–1271 (2016).CrossRefGoogle ScholarPubMed