Details of Grant 

EPSRC Reference:	EP/H005765/1
Title:	Optimising a bioresorbable brushite bone cement for porosity controlled adjustable drug release
Principal Investigator:	Hofmann, Dr M
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Dentistry
Organisation:	University of Birmingham
Scheme:	First Grant - Revised 2009
Starts:	17 May 2010	Ends:	16 May 2011	Value (£):	101,825
EPSRC Research Topic Classifications:	Biomaterials Drug Formulation & Delivery
EPSRC Industrial Sector Classifications:	Healthcare
Related Grants:
Panel History:	Panel Date Panel Name Outcome 04 Jun 2009 Engineering Med, Mech and Mat Panel Announced
Summary on Grant Application Form
The use of bone substitutes is necessary when due to accident, disease or surgical removal extensive amount of bone is lost. However, after bone substitute operations there is an increased risk of bone infection due to an increase in risk factors like weak immune system and diabetes. To treat those infections some bone substitutes like bone cements are now routinely loaded with antibiotics to treat or prevent those infections. The standard bone cement is polymethylmethacrylate (PMMA, practically plexiglass), a polymer that can be moulded or injected into a bone void and then hardens (sets) inside the body after implantation. PMMA has the advantage of superior mechanical properties but has the disadvantages of setting in a heat releasing setting reaction and the possible occurrence of toxic residual unset cement components and may therefore damage the surrounding tissue. Also, due to the heat releasing polymerisation setting reaction of PMMA only a rather limited number of antibiotics can be administered with PMMA. Another artificial bone cement type are bone cements based on calcium phosphates, which are similar to the mineral components of bone. These calcium phosphate cements (CPCs) also set inside the body after implantation but release only negligible heat. They also show a high biocompatibility due to their similarity to bone mineral. These CPCs form either hydroxyapatite, which will only be replaced slowly by new bone (resorption), or they form brushite, a more soluble and therefore more resorbable calcium phosphate. Both types of CaP cement have also been investigated as potential drug release carriers for the treatment or prevention of bone infection as they will allow a wider range of drugs to be incorporated due to the setting reaction that releases almost no heat. However, most of the research has been performed on non or slowly resorbable hydroxyapatite forming cements as they are more robust and mechanically stronger.Recently a high strength brushite forming system has been developed which is similar in mechanical stability to hydroxyapatite forming cement. This was achieved by minimising the porosity of the set cement and maximising the degree of conversion of the cement reactants to brushite. The drug release from a CPC is controlled by diffusion which is controlled by the porosity of the set cement. The established brushite forming CPC can be varied over a wide porosity range. This allows porosity controlled drug release of a large variety of drugs. However, little is known about how these drugs interact with the brushite forming setting reaction and therefore how drug load would affect the porosity and stability of the set cement. The aims of this study are firstly to study the interaction between the setting brushite cement and numerous drugs and the long term impact of the drug`s presence on the resorption of the cement. Secondly to control the release rate of the incorporated drug via the cement`s porosity without compromising mechanical strength and resorption. Thirdly to adjust this new resorbable low porosity cement to allow controlled drug release for a large number of drugs and ultimately to enable a predictable in vivo (inside the body) performance to allow possible application for animal experiments with the long term goal of commercialisation. This project is performed in close collaboration with industrial and international partners.
Key Findings
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Organisation Website:	http://www.bham.ac.uk