Innovative ceramics, cements and composites for diseased bone tissue repair: research, development and innovations.

Project leaders

Daniela Ferro, Sergey Barinov

Agreement

RUSSIA - RAS old - Russian Academy of Sciences old

Call

CNR/RAS 2011-2013

Department

Molecular Design

Thematic area

Chemical sciences and materials technology

Status of the project

Extended

Report for renewal

joint-report-f2008-2010.doc

Research proposal

A considerable part of population suffers from diseases of skeletal bone tissues caused by pathological degradation (osteoporosis), inflammatory processes and cancer. In the developed countries, the number of patients with such chronic diseases reaches about 50% of all population above age 50. According to predictions, due to the overall increase in the life expectancy and the gain in population, the number of aged people will be doubled to 2020. Curing bone tissue diseases, especially malignant growths (osteosarcoma), was often associated with surgical operations that as a rule led to extended post-operative defects. The problem lies in recovery of lost functions of individual organs, parts of skeleton and the whole locomotor apparatus. Two fundamentally different approaches to this problem are feasible, namely, 1) the mechanical replacement of a bone defect by an implant to develop an integral bioengineering structure and 2) the regeneration of damaged bone tissues. Correspondingly, two kinds of materials that differ in their microstructures, properties and in vivo behaviour in the human body were elaborated.
   In the frame of previous bilateral project for the Years 2008-2010, the partners (ISMN CNR and IMET RAS) have performed research & developments directed on the fundamentals of chemistry and technology of advanced and innovative materials of both types. Synthesis methods of different calcium phosphate nanopowders were developed, and the structure and mechanical properties of the nanoceramics were studied. High-strength, high-toughness ceramics were developed intended for applications as implants. The second object of the former project was to develop new composites in the system calcium phosphate - biopolymer(s) and a technology to fabricate those, as well as to reveal the relationship between the structure and the properties of the composites. These composites were demonstrated to be much useful as scaffolding materials in tissue engineering. The third goal was to develop pulsed laser deposited ceramic films on titanium substrates intended for application as orthopaedical implants. All those goals have been achieved successfully and further improvements were attempted to individuate technological procedures for pre-industrial applications. The results were partly introduces into the practice. A numerous of clinical trials were accomplished with these materials successfully.
     During the past decade new innovative materials were developed and transferred into bone regenerative surgery practice and industrial production. Calcium phosphate cements (CPC) are of great interest as biomaterials for bone replacement that are capable of rapid setting to a hard mass, highly biocompatible and gradually replaced by new bone in vivo. Several commercial compositions were introduced in clinical practice and are currently being in use. Despite the relatively long history of CPSs and numerous publications in the field, there is still a lack in the studies of basic properties, such as for example, mechanism of setting reactions and their kinetics, being of great importance for cements application. A number of different combinations of calcium phosphate-containing compounds in the cement systems have been investigated. Among them, octacalcium phosphate (OCP, Ca8H2(PO4)6·5H2O) is considered to be of particular interest, since it has been reported to be a direct precursor phase during the biomineralization process of bones and teeth. The biocompatibility and the osteoconductive nature of synthetic OCP are widely acknowledged. Furthermore, recent studies have shown that OCP enhances a new bone formation, accompanied by its conversion into hydroxyapatite (HA) products and its own biodegradation by the osteoclast cells activities.
            However, up to now only several OCP-based cements have been formulated. Generally, for their preparation two distinctly different methods are used. In particular, in the first work on the development of OCP-based cement it has been reported that mixtures of tricalcium phosphate (TCP) and dicalcium phosphate (DCPA) with water lead to the OCP as reaction product. Contrary, only in very recent work devoted to OCP-based cement it has been shown that the α-TCP and DCPA reaction products were HA or OCP and HA mixture, depending, respectively, on whether water or a phosphate solution are used as liquid phase. Another attempt to obtain the OCP phase in the final product was based on its use as starting reagent. It is known that the transition of OCP into HA is thermodynamically favoured and proceeds spontaneously and irreversibly once initiated. The transformation kinetics and mechanisms, and the final properties of CPCs can be modified, e.g. by biopolymers addition. However, only a few studies are known on the matter. A gap in this field should obviously be eliminated on the way of development of new advanced materials to cover the needs of

Research goals

    The project is aimed at the contribution to the basic knowledge and to the development of innovative technologies of advanced calcium phosphate ceramics, cements and composites of specific performance intended for application in medicine, in particular for the reparation of damaged bone tissues.
- Different synthesis methods will be employed to fabricate the nanopowders:
- precipitation from the aqueous salt solutions;
- hydrolysis of precursor - IMET.To characterize the powders, the following methods will be applied:
 (SEM-EDX) - ISMN; BET specific area and X-ray diffractometry (XRD) - IMET; ( X-ray diffraction - ISMN; (FTIR) - IMET; atomic force microscopy (AFM) .
-Setting and hardening behaviour will be studied by Vikat technique and strength measurements – IMET;Microstructure and phase composition development will be studied . Biopolymer (chitosan, gelatin) will be developed on the basis of cements. Influence of biopolymer on mechanism and kinetics of setting and hardening will be investigated.
The composites will be characterized with respect to their stability in the simulated body fluids, resorbability (IPC), microstructure (ISMN) and mechanical properties (IPC).
- Results of the project and the prototypes will be disseminated through the cooperation with Herzen Moscow Oncological Research Institute, Research Institute of Dentistry and Maxillofacial Surgery, Haematological Research Centre. Pilot-plant production facility will be founded.   

Last update: 08/06/2025