The Significance Of Osteoinductive Biomaterials

Osteoinductive calcium phosphate biomaterials support osteogenic cells to form bone [73]. When in vitro expanded goat bone marrow stromal cells were cultured on a non-osteoinductive calcium phosphate ceramic (HA) and an osteoinductive calcium phosphate ceramic (BCP) for 1 day and thereafter autologously implanted in muscles of goats for 12 weeks, cells on osteoinductive BCP ceramic gave ample bone formation (Figure 10 A), while cells on non-osteoinductive HA ceramic did not give any bone formation (Figure 10 B).

Non Decalcified Bone Pics

Figure 10. Histology of tissue-engineered bone after in vivo implantation. A: Bone formation of tissue-engineered bone with osteoinductive BCP. B: Absence of bone formation in tissue-engineered bone with non-osteoinductive HA. (In vitro expanded goat bone marrow stromal cells were cultured on BCP and HA for 1day and autologously implanted in muscle of goats for 12 weeks, non-decalcified sections, metheylene blue and basic fuchsin staining) [73].

Figure 10. Histology of tissue-engineered bone after in vivo implantation. A: Bone formation of tissue-engineered bone with osteoinductive BCP. B: Absence of bone formation in tissue-engineered bone with non-osteoinductive HA. (In vitro expanded goat bone marrow stromal cells were cultured on BCP and HA for 1day and autologously implanted in muscle of goats for 12 weeks, non-decalcified sections, metheylene blue and basic fuchsin staining) [73].

Non Decalcified Bone Pics

Figure 11. Bone repair with osteoinductive biomaterials. (BCP and HA, having different osteoinductive potentials as indicated in Figure 5, were implanted as cylinders 5mm in diameter, in femur of dogs for different time periods, bone repair was measured as the percentage of the formed bone in pores) [74].

Figure 11. Bone repair with osteoinductive biomaterials. (BCP and HA, having different osteoinductive potentials as indicated in Figure 5, were implanted as cylinders 5mm in diameter, in femur of dogs for different time periods, bone repair was measured as the percentage of the formed bone in pores) [74].

The higher osteoinductive potential the implant materials have, the faster bone repair [74]. Osteoinductive calcium phosphate biomaterials in the one hand provide a good environment for osteogenic cells to form bone and on the other hand induce non-osteogenic cells to differentiate into osteogenic cells that then form bone. Theoretically, osteoinductive calcium phosphate biomaterials give faster bone formation in bone repair. Fast bone formation in theory happened in practice as shown in a comparison of two calcium phosphate ceramics (BCP and HA). As discussed previously, BCP ceramic has a higher osteoinductive potential than HA when exhibiting similar porous structures (both macropores and micropores). When ceramic cylinders (5mm in diameter) of both BCP and HA were implanted intracortically in femurs of dogs for different time periods of 7days, 14day, 21day, 30days, 45days and 60days, more bone was formed in BCP than HA at day 14, day 21 and day 30 (Figure 11). The bone defects have been repaired by BCP in 30 days after implantation because the formed bone remained stable after 30days, while the bone defects were repaired two weeks later with HA than with BCP. In addition to the fast bone repair in small bone defects, osteoinductive calcium phosphate biomaterials are expected to repair critical bone defects, since bone formation occur far from the host bone bed by osteoinduction in large bone defects. When an osteoinductive BCP ceramic was used to repair a well-established critical bone defect (17mm in diameter) in iliac wing of goats, after 12 weeks bone formation has already forwarded to 6.3+1.7mm far from the host bone bed (74% of the total length of the defect). Newly formed bone could sometimes even be found throughout the implant (100% of the total length) (Figure 12). Compared to the bone repair with allograft and autograft in the same model at the same time period, bone formation in osteoinductive BCP is much better than allograft and equal to autograft [75].

Ileal Wing

Figure 12. Repair of a critical defect in iliac wing of goat. (Osteoinductive BCP ceramic discs, 017x6mm, were implanted in iliac wing of goats for 12 week, a pseudocolored image, Red: bone,

Figure 12. Repair of a critical defect in iliac wing of goat. (Osteoinductive BCP ceramic discs, 017x6mm, were implanted in iliac wing of goats for 12 week, a pseudocolored image, Red: bone,

4. The Future Challenges

It is obvious that calcium phosphate biomaterials can be made osteoinductive through physicochemical modification besides by additional introduction of growth factors or osteogenic cells. It appears that osteoinductive calcium phosphate biomaterials are good biomaterials for bone repair. The osteoinductive potentials of calcium phosphate biomaterials are material-dependent. Some material factors affecting osteoinductive potentials have been identified, but not fully understood. The full understanding of material factors relevant to bone formation induced by calcium phosphate biomaterials may result in calcium phosphate biomaterials with higher and higher osteoinductive potentials which can induce bone formation as early as possible and induce as much bone formation as possible, and therefore repair bone as fast as possible and as large as possible.

Apart from osteoconductive property and osteoinductive property, bone grafts require other properties. An ideal bone graft should be osteoconductive, osteoinductive, resorbable, easy to shape and have good mechanical properties. New techniques are necessary to implement calcium phosphate biomaterials according to the clinical requirements.

How far away osteoinductive calcium phosphate biomaterials can go in bone repair is not known as yet. However, even though osteoinductive potentials of calcium phosphate biomaterials alone are still not effective enough for bone repair, osteoinductive biomaterials could be used as bone tissue engineering scaffold, growth factor carrier, gene carrier or extender of autograft.

From no bone to bone, bone formation induced by calcium phosphate biomaterials serves a good model to study bone biology and bone physiology. The mechanism of bone formation by osteoinductive biomaterials is not clear as yet, however, the more understanding of such mechanism in the future may, in the one hand help us understand more about bone and bone repair, and on the other hand help us improve osteoinductive biomaterials.

At last but not least, graft is only a part of bone repair, other things including the instrumentation and fixation are also very important for bone regeneration and bone repair [3-11]. In other words, a bridge is needed to bring osteoconductive, osteoinductive calcium phosphate biomaterials to clinics for bone repair.

References

1. Bloom, W. and Fawcettt, D.W. (1986) A textbook of histology, W. B. Saunders, Philadelphia, pp. 199-238.

2. Rosenberg, A. (1999) Bones, joints, and soft tissue tumors, in R.S. Cotran, V. Kumar and T. Collins (eds) Robins pathological basis of disease, W. B. Saunders, Philadelphia, pp. 1215-1268.

3. Damien, C.J. and Parsons, J.R. (1991) Bone graft and bone graft substitutes: A review of current technology and application, J.Appl.Biomat. 2, 187-208.

4. Hollinger, J.O., Brekke, J., Gruskin, E, and Lee, D. (1996) Role of bone substitutes, Clin.Orthop. 324, 55-65.

5. Perry, C.R. (1999) Bone repair techniques, bone graft, and bone graft substitutes, Clin.Orthop. 360, 71-86.

6. Betz, R.R. (2002) Limitations of autograft and allograft: new synthetic solutions, Orthopedics 25, s561-570.

7. Parikh, S.N. (2002) Bone graft substitutes: past, present, future, J. Postgrad. Med. 48,142-8.

8. McAuliffe, J.A. (2003) Bone graft substitutes, J. Hand Ther. 16,80-187.

9. Costantino, P.D., Hiltzik, D., Govindaraj, S. and Moche, J. (2002) Bone healing and bone substitutes, Facial Plast. Surg. 18, 13-26.

10. Sammarco, V.J. and Chang, L. (2002) Modern issues in bone graft substitutes and advances in bone tissue technology, Foot Ankle Clin. 7, 19-41.

11. Bucholz, R.W,. (2002) Nonallograft osteoconductive bone graft substitutes, Clin. Orthop. 395, 4452

12. Hench, L.L. (1980) Biomaterials, Science 208, 826-831.

13. Jarcho, M. (1981) Calcium phosphate ceramics as hard tissue prosthetics, Clin.Orthop. 157, 259278.

14. Hench, L.L. and Wilson, J. (1984) Surface-active biomaterials, Science 226, 630-635.

15. de Groot K. (1984) Calcium phosphate ceramics: their current status, in J.W. Boretos, and M. Eden (eds), Contemporary Biomaterials. Noyes Publications, USA, pp. 477-492.

16. Daculsi, G. and Passuti, N. (1989) Bioactive ceramics, fundamental properties and clinical applications: the osteo-coalescence process, Bioceramics 2, 3-10.

17. Osborn, J.F. (1991) The biological profile of hydroxyapatite ceramic with respect to the cellular dynamics of animal and human soft tissue and mineralized tissue under unloaded and loaded conditions, in M.A. Barbosa (eds), Biomaterials Degradation, Elsevier, Amsterdam, pp. 185-225.

18. Daculsi, G. (1998) Biphasic calcium phosphate concept applied to artificial bone, implant coating and injectable bone substitute, Biomaterials 19, 1473-1478.

19. Szpalski, M., and Gunzburg, R. (2002) Applications of calcium phosphate-based cancellous bone void fillers in trauma surgery, Orthopedics 25, s601-609.

20. Metseger, D.S. and Driskell, T.D. (1982) Tricalcium phosphate ceramic, a resorbable bone implant: Review and current status, J. Am. Dent.Assoc. 105, 1035-1044.

21. Nakamura, T., Yamamura, T., Higashi, S., Kokubo, T. and Itoo, S. (1985) A new glass-ceramic for bone replacement: Evaluation of its bonding to bone tissue, J. Biomed. Mater. Res. 19, 685698.

22. El-Ghannam, A., Ducheyne, P. and Shapiro, I.M. (1997) Formation of surface reaction products on bioactive glass and their effects on the expression of osteoblastic phenotype and the deposition of mineralized extracellular matrix, Biomaterials 18, 295-303.

23. Kokubo, T., Kim, H.M. and Kawashita, M. (2003) Novel bioactive materials with different mechanical properties, Biomaterials 24, 2161-2175.

24. Ginebra, M.P., Fernandez, E., Boltong, M.G., Planell, J.A., Bermudez, O. and Driessens, F.C.M. (1994) Compliance of a calcium phosphate cement with some short-term clinical requirement, Bioceramics 6, 273-278.

Miyamoto, Y., Ishikawa, K., Fukao, H., Sawada, M., Nagayama, M., Kon, M. and Asaoka, K.

(1995) In vivo setting behaviour of fast-setting calcium phosphate cement, Biomaterials 16, 855860.

Miyamoto, Y., Ishikawa, K., Takechi, M., Yuasa, M., Kon, M., Nagayama, M. and Asaoka, K.

(1996) Non-decay type fast-setting calcium phosphate cement: setting behavior in calf serum and its tissue response, Biomaterials 17, 1429-1435.

Constantz, B.R., Barr, B.M., Ison, I.C., Fulmer, M.T., Baker, J., McKinney, L., Goodman, S.B., Gunasekaren, S., Delaney, D.C., Ross, J. and Poser, R.D. (1998) Histological, chemical, and crystallographic analysis of four calcium phosphate cements in different rabbit osseous sites, J. Biomed. Mater. Res. 43, 451-461.

Yuan, H., Li, Y., de Bruijn, J.D., de Groot, K. and Zhang, X. (2000) Tissue responses of calcium phosphate bone cement: A study in dogs, Biomaterials 21, 1283-1290.

de Groot, K., Geesink, R., Klein, CPAT and Serekian, P. (1987) Plasma sprayed coatings of hydroxyapatite, J. Biomed. Mater. Res. 21,1375-1381.

Cook, S.D., Thomas, K.A., Kay, J.F. and Jarcho, M. (1988) Hydroxyapatite-coated porous Titanium for use as an orthopedic biologic attachment system, Clin.Orthop. 230, 303-311. Vercaigne, S., Wolke, J.G.C., Naert, I. And Jansen, J.A. (1998) Bone healing capacity of titanium plasma-sprayed and hydroxyapatite-coated oral implants, Clin. Oral implants Res. 9, 261-271. Lacefield, W.R. (1998) Current status of ceramic coatings for dental implants, Implant Dent. 7, 315-322.

Abe, Y., Kokubo, T. and Yamamura, T. (1990) Apatite coating on ceramics, metals and polymers utilizing a biological process, J.Mater.Sci: Mater.Med 1, 233-238.

Leitao, E., Barbosa, M.A. and de Groot, K. (1995) In vitro calcification of orthopaedic implant materials, J. Mater. Sci: Mater. Med 5, 849-852.

Wen, H.B., de Wijn, J.R,. van Blitterswijk, C.A. and de Groot, K. (1999) Incorporation of bovine serum albumin in calcium phosphate coating on titanium, J. Biomed. Mater. Res. 46, 245-252. Liu, Y., Hunziker, E.B., Layrolle, P. and de Groot, K. (2002) Introduction of ectopic bone formation by BMP-2 incorporated into calcium phosphate coatings of Titanium-Alloy implants, Bioceramics 15, 667-670.

Fujibayashi, S., Nakamura, T., Nishiguchi, S., Tamura, J., Uchida, M. and Kim, H.M. (2001) Kokubo T, Bioactive titanium: effect of sodium removal on the bone-bonding ability of bioactive titanium prepared by alkali and heat treatment, J. Biomed. Mater. Res. 56,562-570. Zardiackas, L.D., Teasdall, R.D., Black, R.J., Jones, J.S., St.John, R., Dillion, L.D. and Hughes, J.L. (1994) Torsional properties of healed canine diaphyseal defects grafted with a fibrillar collagen and hydroxyapatite/tricalcium phosphate composite, J. Appli. Biomater. 5, 277-283. John, R.K., Zardiackas, L.D., Terry, R.C., Teasdall, R.D. and Cooke, S.E. (1995) Histological and electron microscopic analysis of tissue response to synthetic composite bone graft in the canine, J. Appl. Biomater. 6, 89-97.

Lawson, A.C. and Czernuszka, J.T. (1998) Collagen--calcium phosphate composite, Proc. Inst. Mech. Eng. 212, 413-425.

Muzzarelli, C. and Muzzarelli, R.A. (2002) Natural and artificial chitosan-inorganic composites, J. Inorg. Biochem. 92, 89-94.

Roy, I., Mitra, S., Maitra, A. and Mozumdar, S. (2003) Calcium phosphate nanoparticles as novel non-viral vectors for targeted gene delivery, Int. J. Pharm. 250, 25-33.

Forster, S. and Plantenberg, T. (2002) From self-organizing polymers to nanohybrid and biomaterials, Angew Chem. Int. Ed. Engl. 41, 689-714.

Urist, M.R. (1965) Bone: formation by autoinduction, Science 150, 893-899.

Urist, M.R., Huo, Y.K. and Brownell, A.G. (1984) Purification of bovine bone morphogenetic protein by hydroxyapatite chromatography, Proc.Natl.Acad.Sci.USA 81, 371-375.

Yamasaki, H. (1990) Heterotopic bone formation around porous hydroxyapatite ceramics in the subcutis of dogs, Jpan. J. Oral Biol. 32, 190-192.

Ripamonti, U. (1991) The morphogenesis of bone in replicas of porous hydroxyapatite obtained from conversion of calcium carbonate exoskeletons of coral, J. Bone & Joint Surg. 73A, 692-703. Zhang, X. (1991) A study of porous block HA ceramics and its osteogenesis, in A. Ravaglioli and A. Krajewski (eds), Bioceramics and the Human Body, Elsevier Science, Amsterdam, pp. 408415.

Vargervik K. (1992) Critical sites for new bone formation, In M.B. Habal and A.H. Reddi (eds), Bone grafts & bone substitutes, W.B. Saunders, Philadelphia, pp.112-120.

Yamasaki, H. and Saki, H. (1992) Osteogenic response to porous hydroxyapatite ceramics under the skin of dogs, Biomaterials 13, 308-312.

Toth, J.M., Lynch, K.L. and Hackbarth, D.A.(1993) Ceramic-induced osteogenesis following subcutaneous implantation of calcium phosphates, Bioceramics 6, 9-13.

Klein, CPAT, de Groot, K., Chen, W., Li, Y. and Zhang, X. (1994) Osseous substance formation induced in porous calcium phosphate ceramics in soft tissues, Biomaterials 15, 31-34. Green, J.P., Wojno, T.H., Wilson, M.W. and Grossniklaus, H.E. (1995) Bone formation in hydroxyapatite orbital implants, Am. J. Ophthalmol. 120, 681-682.

Ripamonti, U. (1996) Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models, Biomaterials 17, 31-35.

Yang, Z., Yuan, H., Tong, W., Zou, P., Chen, W. and Zhang, X. (1996) Osteogenesis in extraskeletally implanted porous calcium phosphate ceramics:variability among different kinds of animals, Biomaterials 17, 2131-2137.

Yang, Z., Yuan, H., Zou, P., Tong, W., Qu, S. and Zhang, X. (1997) Osteogenic responses to extraskeletally implanted synthetic porous calcium phosphate ceramics: an early stage histomorphological study in dogs. J. Mater. Sci: Mater. Med. 8, 697-701.

Sires, B.S., Holds, J.B., Kincaid, M.C. and Reddi, A.H. (1997) Osteogenin-enhanced bone-specific differentiation in hydroxyapatite orbital implants, Ophthal. Plast. Reconstr. Surg. 13, 244251

Yuan, H., Yang, Z., Li, Y., Zhang, X., de Bruijn, J.D. and de Groot, K. (1998) Osteoinduction by calcium phosphate biomaterials, J. Mater. Sci: Mater. Med. 9, 723-726.

de Bruijn, J.D., Dalmeijer, R. and de Groot, K. (1999) Osteoinduction by microstructured calcium phosphates, Transaction of 25th Annual meeting of Society for Biomaterials, RI, USA, p235. Yuan, H., Kurashina, K., de Bruijn, J.D., Li, Y., de Groot, K. and Zhang, X. (1999) A preliminary study on osteoinduction of two kinds of calcium phosphate ceramics, Biomaterials 20, 1799-1806. Ripamonti, U., Crooks, J. and Kirkbride, A.N. (1999) Sintered porous hydroxyapatite with intrinsic osteoinductive activity: geometric induction of bone formation, South African Journal of Science 95, 335-343.

de Bruijn, J.D., Yuan, H., Dekker, R. and van Blitterswijk, C.A. (2000) Osteoinduction by biomimetic calcium phosphate coatings and their potential use as tissue engineering scaffolds. in J. E. Davies (eds), Bone engineering, em squared incorporated, Toronto, pp.421-431. Yuan. H., de Bruijn, J.D., Li, Y., Feng, J., Yang, Z., de Groot, K. and Zhang, X. (2001) Bone formation induced by calcium phosphate ceramics in soft tissue of dogs: A comparative study between a-TCP and ß-TCP, J. Mater. Sci: Mater. Med. 12, 7-13.

Yuan, H., Yang, Z., de Bruijn, J.D., de Groot, K. and Zhang, X. (2001) Material-dependent bone induction by calcium phosphate ceramics: A 2.5-year study in dog, Biomaterials 22, 2617-2623. Yuan, H., de Bruijn, J.D., Zhang, X., van Blitterswijk, C.A. and de Groot, K. (2001) Bone induction by porous glass ceramic made from Bioglass (45S5), J. Appl. Biomat. 58, 270-276. Yuan, H., de Bruijn, J.D., van Blitterswijk, C.A. and de Groot, K. (2001) Bone induction by a calcium phosphate ceramic in rabbits. Transaction of 27th Annual meeting of society for biomaterials, Minnesota, USA, pp.142.

Gosain, A.K., Song, L.,Riordan, P., Amarante, M.T., Nagy, P.G., Wilson, C.R., Toth, J.M., and

Ricci, L. (2002) A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part I, Plastic andReconstructuve Surgery 109, 619-630.

Kurashina, K., Kurita, H., Wu, Q., Ohtsuka, A., and Kobayashi, H. (2002) Ectopic ostepgenesis with biphasic ceramics of hydroxyapatite and tricalcium phosphate in rabbits, Biomaterials 23,

Was this article helpful?

+1 0
Accomplishing Your True Calling

Accomplishing Your True Calling

Align Yourself To Your Passions And Take On The World With Your Power! Let your heart and soul help you discover the correct course. Take note that the word courage is in the word encouragement. Once we identify the course with a heart and soul, we feel boosted to get moving.

Get My Free Ebook


Responses

  • NORBERTO
    How to repair bone Time?
    4 years ago

Post a comment