Abstract
Approximately 5 – 10% of all bone fractures are associated with impaired healing. It is thought that regenerative medicine has the potential to improve on existing treatments for non-union fractures, and the European market for such treatments is projected to reach £2.2 billion in 2010. The use of scaffolds for the delivery of both growth factors and human Marrow Stromal Cells (hMSCs) is thought to be a promising approach. It may be desirable to promote proliferation and chemotaxis of hMSCs at the defect site shortly after implantation, and differentiation in the longer term. This is likely to require a dual delivery system, capable of releasing multiple drugs with different release profiles. Our aim has been to develop a polymer scaffold capable of releasing bioactive molecules that are able to direct the differentiation of primary hMSCs down the osteoblastic lineage. We have examined two mutually compatible drug delivery systems: collagen coating for short term release, and polymer encapsulation for longer term release.
Polymer scaffolds were manufactured and coated with Type I Collagen containing BMP-7. hMSCs from three different patient sources were exposed to the scaffolds for 14 days. The cells were then histochemically stained for Alkaline Phosphatase (ALP) and photographed. The areas of ALP staining were then normalised against the total cell count.
Normalised ALP expression was increased compared to the controls for three different patients (‘110 ± 39% SE, n=6, p=0.005’, ‘540 ± 270% SE, n=6, p=0.001’, and ‘32 ± 17% SE, n=6’). Scaffolds were also manufactured either with 1,25 Vitamin D3 (another active compound) in a coating of Collagen, or encapsulated using proprietary methodologies. It was found that both treatments significantly increased normalised Alkaline Phosphatase expression within the 14d experimental period demonstrating release of the active 1,25 Vitamin D3 (’88 ± 37% SE, n=6, p=0.012’ and ‘100 ± 32% SE, n=6, p=0.012’ respectively).
Our findings suggest that, subject to future testing and development, such bioactive scaffolds could form the basis for a dual drug delivery system, suitable for applications in bone regenerative medicine.
Correspondence should be addressed to Dr Roger Bayston, Division of Orthopaedic and Accident Surgery, Queen’s Medical Centre, Nottingham, NG7 2UH, England.
