Calcium Phosphate Cements as Carriers of Functional Substances for the Treatment of Bone Tissue

Abstract

Interest in calcium phosphate cements as materials for the restoration and treatment of bone tissue defects is still high. Despite commercialization and use in the clinic, the calcium phosphate cements have great potential for development. Existing approaches to the production of calcium phosphate cements as drugs are analyzed. A description of the pathogenesis of the main diseases of bone tissue (trauma, osteomyelitis, osteoporosis and tumor) and effective common treatment strategies are presented in the review. An analysis of the modern understanding of the complex action of the cement matrix and the additives and drugs distributed in it in relation to the successful treatment of bone defects is given. The mechanisms of biological action of functional substances determine the effectiveness of use in certain clinical cases. An important direction of using calcium phosphate cements as a carrier of functional substances is the volumetric incorporation of anti-inflammatory, antitumor, antiresorptive and osteogenic functional substances. The main functionalization requirement for carrier materials is prolonged elution. Various release factors related to the matrix, functional substances and elution conditions are considered in the work. It is shown that cements are a complex system. Changing one of the many initial parameters in a wide range changes the final characteristics of the matrix and, accordingly, the kinetics. The main approaches to the effective functionalization of calcium phosphate cements are considered in the review.

Keywords: antibiotics; antitumor drugs; bone tissue; brushite; calcium phosphate cement; functionalization; growth factors; hydroxyapatite; osteomyelitis; treatment.

Figure 1

Schematic representation of the stages of fracture self-healing: (I) The acute stage of the fracture, a hematoma forms around the damaged area of the bone, the bone tissue of the ends of the fragments partially dies (colored dark), local enzymatic activity increases. (II) Development of connective tissue corn. Accompanied by inflammation: cells participating in the inflammatory response appear at the site of the fracture; osteoclasts and osteoblasts are active, non-viable tissue is processed; with the formation of a “cloud” of new tissue at the site of the fracture, structured bone bridges appear inside the corn connecting the fragments. (III) Consolidation: the newly formed tissue acquires the correct bone structure, and trabeculae appear. (IV) Remodeling: the newly formed bone acquires its final structure.

Figure 2

Scheme of the development of hematogenous osteomyelitis in the bone. (I) Formation of a primary bone abscess (necrosis and purulent fusion of the bone marrow and adjacent bone, limited by the walls of healthy tissue). (II) Subperiosteal abscess (pus through the haversian canals of the bone spreads under the periosteum, exfoliating it from the bone). (III) Fistula formation (pus breaks out through soft tissues); the formation of sequesters is possible—areas of the bone completely devoid of vascular nutrition and lying freely.

Figure 3

Development of a bone tumor: (I) Destruction of a bone site by a tumor; (II) replacement of healthy bone tissue with tumor tissue, inclusion of the bone marrow canal and soft tissues in the pathological process.

Figure 4

Comparison of osteoporosis and healthy bone: decrease in bone density, and thinning of bone structures, as a result of osteoporosis.

Figure 5

Diagram of applicability of calcium phosphate cements.

Figure 6

Scheme of replacement of bone defects with the help of calcium phosphate material: (I) Formation of a defect along the boundaries of viable tissues (resection of compromised areas as a result of high-energy trauma, inflamed areas in osteomyelitis, tumor lesions, etc.). (II) Installation of metal structures for mechanical strength for the period of healing and implantation of osteoplastic material to close the defect. (III) Reconstruction of osteoplastic material in the defect, resorption, biodegradation and formation of bone. (IV) Bone remodeling.