Using Calcium Phosphate to Heal Bone Defects

Bone defects arising as a consequence of trauma or disease typically require surgical intervention to promote healing. The defect must be filled to provide a framework to support and encourage the growth of new, living bone.

The gold standard for filling bone defects is autologous bone, but the additional morbidity involved for the patient in harvesting bone for grafting has led to a growing preference for alternative methods. The need for further surgery to acquire the bone is eliminated by using donated bone, but such allografts carry the risk of an immune response preventing the graft from being accepted.

Consequently, the use of synthetic bone graft materials is steadily gaining popularity.¹ A variety of bone graft substitutes have been used in the search to find an alternative to bone that provides a rapid and strong repair. These include demineralized bone matrix, calcium phosphates, collagen- and hydroxyapatite-based substitutes, and bone morphogenetic proteins. This article will focus on calcium phosphate ceramics and bioactive glasses.

Calcium Phosphates for Synthetic Bone Grafts

Calcium phosphate ceramics closely resemble the mineral components naturally present in bone tissue, and so represent an attractive option for a synthetic bone filling material. Their biocompatibility and ready availability have led to calcium phosphate ceramics being widely used as an alternative to autografts and allografts.

Calcium phosphates have proven to result in good cell attachment when used as bone substitutes and tissue engineering scaffolds. They are also known to provide predictable outcomes and lower morbidity for the patient whilst being cost effective compared with traditional bone grafts.^2,3

Initially, calcium phosphate ceramics lacked sufficient porosity to allow immediate bone ingrowth and rapid integration into the bone tissue. However, variations in the parameters used during the preparation of calcium phosphates has led to the production of products with more favorable chemical and physical characteristics, such as specific surface areas and porosity.

Careful selection of the precise combination of properties has enabled development of bone filling materials that improve the adhesion, proliferation and differentiation of cells, thereby allowing improved osteoconductivity.⁴

Bioactive Glasses

Bioactive glass is a particularly favorable form of synthetic bonegraft as it is osteoconductive, bioactive and antimicrobial. In addition, minerals, such as calcium, are released from the bioactive glass providing key substrates for the production of new bone.

Bioactive glass induces specific biological activity when implanted in the body that causes an amorphous calcium phosphate layer to develop on its surface. Over a few hours, this layer incorporates blood proteins and collagen and crystallizes into hydroxycarbonate apatite, which makes it very similar to natural bone mineral. Bioactive glass thus bonds readily to the recipient bone.

Furthermore, the properties of bioactive glass, such as particle size and rate of reabsorption, can be tailored by adjusting the exact composition to meet the requirements of a specific repair procedure.^4,5

Bioactive Glasses Encourage Bone Repair

Bioactive glass has been successfully used in a range of tissue engineering procedures.³ With its versatility, achieved through the tailoring of properties, its intrinsic strength and biocompatibility, bioactive glass presents many of the features needed in a synthetic bone substitute.

Bioactive glass bone filler composites have also been loaded with drugs, proteins and growth factors to facilitate repair by delivering the therapeutic agents directly into the defect region.⁷

It has been shown that damaged bone regained its original strength more quickly when repaired using a composite bone filler material that included bioactive glass compared with bone repair using composite alone. Furthermore, when bioactive glass is added to the bone substitute, the efficacy achieved is comparable to that obtain with the gold standard—autologous bone grafting. A bioactive glass synthetic bone substitute was recently shown to be effective in the repair of cavitary bone defects in patients with chronic osteomyelitis.⁸

Bioactive glass has also shown great promise in a variety of other orthopedic applications including spinal fusion and the coating of implants and the strengthening of bone at the site of joint replacements, plates, or screws. Bioactive glass coatings on orthopedic implants did not induce any adverse effects or inflammatory response in the surrounding tissue.⁹ Furthermore, bioactive glass coatings accelerated cell attachment, spreading, proliferation, differentiation, and mineralization of the extracellular matrix and promoted rapid bone growth. Spine fusion performed in rabbits using a mineralized collagen bone substitute with and without added bioactive glass demonstrated that the addition of bioactive glass led to earlier fusion of the bone. In addition, the addition of bioactive glass achieved a repair very similar to that seen with autograft in terms of the amount and quality of the new bone.¹⁰

Mo-Sci produce implant grade bioactive glass in a variety of forms suitable for a range of bone repair applications, and can tailor its composition to meet specific requirements.⁵ The composition and form of the bioactive glass can be adjusted to match the intrinsic conditions of the patient and the rate and pattern of bone formation required.⁴

References and Further Reading

1. Kinaci A, et al. Trends in Bone Graft Use in the United States. Orthopedics 2014;37(9):e783 e788.
2. Saffar JL, et al. Bone formation in tricalcium phosphate-filled periodontal intrabony lesions. Histological observations in humans. J Periodontol 1990;61(4):209–216.
3. Barrère F, et al. Bone regeneration: Molecular and cellular interactions with calcium phosphate ceramics. Int. J. Nanomed. 2006, 1, 317–332.
4. Lobo SE, et al. Biphasic Calcium Phosphate Ceramics for Bone Regeneration and Tissue .Engineering Applications. Materials 2010;3:815-826.
5. Mo Sci Corporation website. http://www.mo-sci.com/en/products
6. Jia W, et al. Bioactive Glass for Large Bone Repair. Adv Health Mater. 2015;4(18):2842 2848.
7. Schumacher M, et al. Calcium phosphate bone cement/mesoporous bioactive glass composites for controlled growth factor delivery. Biomater. Sci. 2017;5:578 588.
8. Ferrando A, et al. Treatment of Cavitary Bone Defects in Chronic Osteomyelitis: Biogactive glass S53P4 vs. Calcium Sulphate Antibiotic Beads. Bone Jt Infect. 2017;2(4):194 201.
9. Mehdikhani-Nahrkhalaji M, et al. Biodegradable nanocomposite coatings accelerate bone healing: In vivo evaluation. Dent Res J (Isfahan). 2015;12(1):89 99.
10. Pugely AJ, et al. Influence of 45S5 Bioactive Glass in A Standard Calcium Phosphate Collagen Bone Graft Substitute on the Posterolateral Fusion of Rabbit Spine. Iowa Orthop J. 2017; 37: 193–198.