In Vitro and In Vivo Evaluations of 3D Porous TCP-coated and Non-coated Alumina Scaffolds

Abstract

Both tricalcium phosphate (TCP) and alumina have been extensively studied and shown to have high biocompatibility. Tricalcium phosphate has improved biodegradability and a higher solubility than hydroxyapatite. In contrast, alumina (Al₂O₃) is almost completely inert at physiological conditions and has been used as a biomaterial due to its wear resistance, high surface finish, and excellent hardness. Thus, the combination of these two implants would result in greater biocompatibility and phenotype maintenance. A polyurethane (PU) foam replica method was employed in this study to coat TCP on an alumina scaffold. The TCP-coated alumina scaffold was then sintered to generate a porous surface morphology. The pore sizes obtained using this approach ranged between 100—600 µm, which is ideal for cellular proliferation. The cytotoxicity, cellular proliferation, differentiation, and ECM deposition on the coated scaffold resulted in longer-term viability of osteogenic markers compared to the non-coated scaffold. Moreover, the osteogenic properties of porous TCP-coated Al₂O₃ scaffolds were reported in this study using rabbit models. The TCP/Al₂O₃ scaffold and control Al₂O₃ scaffolds were implanted in the rabbit femur. The bone tissue response was analyzed with micro-computed tomography (micro CT) at 12 and 24 weeks after implantation. The porous scaffolds exhibited favorable hard and soft tissue responses at both time points. At 24 weeks, a three-fold increase in bone tissue ingrowth was observed in defects containing TCP-coated Al₂O₃ scaffolds compared to control Al₂O₃ scaffolds.

Keywords

tricalcium phosphate biocompatibility cytotoxicity ECMs micro-CT alumina scaffold.

Get full access to this article

View all access options for this article.

References

Langer, R. and Vacanti, J.P. Tissue Engineering, Science, 1993: 260: 920-926.

Risbud, M. Tissue Engineering: Implications in the Treatment of Organ and Tissue Defects , Biogerontology, 2001: 2: 112-125.

Causa, F. , Netti, P.A. and Ambrosio, L. A multi-Functional Scaffold for Tissue Regeneration: The Need to Engineer a Tissue Analogue, Biomaterial, 2007: 28: 5093-5099.

Gross, K.A. and Rodriguez-Lorenzo, L.M. Biodegradable Composite Scaffolds with an Interconnected Spherical Network for Bone Tissue Engineering, Biomaterials, 2004: 25: 4955-4962.

Akay, G. , Birch, M.A. and Bokhari, M.M. Microcellular Poly HIPE Polymer Supports Osteoblast Growth and Bone Formation In Vitro, Biomaterials, 2004: 25: 3991-4000.

Laffargue, P. , Breme, J. , Helsen, J.A. and Hildebrand, H.F. ( 1998). Retrieval Analyses. In: Helsen, J.A. and Breme, H.J. (eds), Metals as Biomaterials, Chichester, John Wiley & Sons, pp. 467-501.

Yang, P. et al. Activation of platelets adhered on amorphous hydrogenated carbon (a-C:H) films synthesized by plasma immersion ion implantation- deposition (PIII-D), Biomaterials, 2003: 24: 2821-2829.

Hildebrand, H.F. , Blanchemain, N. , Mayer , G. , et al. Surface Coatings for Biological Activation and Functionalization of Medical Devices, Surf. Coat. Technol. , 2006: 200: 6318-6324.

Klein, C.P.A.T. , Driesssen, A.A. , de Groot, K. and van den Hoof , A. Biodegradation Behavior of Various Calcium Phosphate Materials in Bone Tissue, J. Biomed. Mater. Res., 1983: 17: 769-784.

10.

Ducheyne, P. , Radin, S. and King, L. The Effect of Calcium Phosphate Ceramic Composition and Structure on In Vitro Behavior. I. Dissolution, J. Biomed. Mater. Res., 1993: 27: 25-34.

11.

Uchida, A. , Nade, S.M.L. , MacCartney, E.R. and Ching, W. The Use of Ceramics for Bone Replacement: A Comparative Study of 3 Different Porous Ceramics, J. Bone Joint Surg., 1984 : 66: 269-275.

12.

Bucholz, R.W. , Carlton, A. and Holmes, R.E. Hydroxyapatite and Tricalcium Phosphate Bone Graft Substitutes, Orthop. Clin. N. Am., 1987: 18: 323-334.

13.

Cao, W. and Hench, L.L. Bioactive Materials, Ceram. Int., 1996: 22: 493-507.

14.

Bohner, M. Calcium Orthophosphates in Medicine: From Ceramics to Calcium Phosphate Cements , Injury, 2003: 31: 37-47.

15.

Wiesmann, H.P. , Joos, U. and Meyer, U. Biological and Biophysical Principles in Extracorporal Bone Tissue Engineering. Part II, Int. J Oral Maxillofac. Surg., 2004: 33: 523-530.

16.

Shackelford, J.F. Bioceramics - Current Status and Future Trends, Bioceram. Mater. Sci. Forum., 1999 : 293: 99-106.

17.

Lee, J.S. (2008). Alumina. In: Wnek, G.E. and Bowlin, G.L. (eds), Encyclopedia of Biomaterials and Biomedical Engineering, 2nd edn, New York, Informa Healthcare, Vol. 1, pp. 17-25.

18.

Price, R.L. , Haberstroh, K.M. and Webster, T.J. Enhanced functions of Osteoblasts on Nanostructured Surfaces of Carbon and Alumina , Med. Biol. Eng. Comput., 2003: 41: 372-375.

19.

Karen, J.L. , Burg, S.P. and Kellam, J.F. Biomaterial Developments for Bone Tissue Engineering, Biomaterials, 2000: 21: 2347-2359.

20.

Moreira, E.A. , Innocentini, M.D.M. and Courry, J.R. Permeability of Ceramic Foams to Compressible Flow, J. Euro. Ceram. Soc. , 2004: 24: 3209-3218.

21.

Han, J.K. , Song, H.Y. , Saito, F. and Lee , B.T. Synthesis of high purity nanosize hydroapatite powder by microwave-hydrothermal method, Mater Chem. Phy. , 2006: 99: 235-239.

22.

Mickisch, G. , Fajta, S. , Keilhauer , G. , et al. Chemosensitivity Testing of Primary Human Renal Cell Carcinoma by a Tetrazolium Based Microculture Assay (MTT) , Urolo Res., 1990: 18: 131-136.

23.

Nehrer, S. , Nehrer, H.A. , and Breinan, A. et al. Matrix Collagen Type and Pore Size Influence Behaviour of Seeded Canine Chondrocytes, Biomaterials, 1997: 18: 769-776.

24.

Miot, S. , Woodfield, T. , Daniels, A.U. et al. Effects of Scaffold Composition and Architecture on Human Nasal Chondrocyte Redifferentiation and Cartilaginous Matrix Deposition, Biomaterials, 2005: 26: 2479-2489.

25.

Zhao, K. , Deng, Y. and Chen, G.Q. Effects of Surface Morphology on the Biocompatibility of Polyhydroxyalkanoates , J. Biochem. Eng., 2003: 16: 115-123.

26.

Cheng, Z. and Teoh, S.H. Surface Modification of Ultra Thin Poly (caprolactone) Films Using Acrylic Acid and Collagen, Biomaterials, 2004 : 25: 1991-2001.

27.

Attawia, M.A. , Herbert, K.M. and Laurencin , C.T. Osteoblast-Like Cell Adherence and Migration through 3-Dimensional Porous Polymer Matrices , Biochem. Biophys. Res. Commun., 1995: 213: 639-644.

28.

Silkavitsas, V.I. , Bancroft, G.N. and Mikos, A.G. Formation of Three-Dimensional Cell/Polymer Constructs for Bone Tissue Engineering in a Spinner Flask and a Rotating Wall Vessel Bioreactor, J. Biomed. Mater. Res., 2002: 62: 136-148.

29.

Howlette, C.R. , Evans, M.D.M. , Walsh, W.R. , Johnson, G. and Steele, J.G. Mechanism of Initial Attachment of Cells Derived from Human Bone to Commonly Used Prosthetic Materials during Cell Culture, Biomaterials, 1994: 15: 213-222.

30.

Rajaraman, R. , Rounds, D.E. , Yen , P.S. and Rembaum, A.A. Scanning Electron Microscope Study of Cell Adhesion and Spreading In Vitro, Exp. Cell. Res., 1974: 88: 327-339.