Biofunctionalization of cancellous bone allografts for the therapy of critical size bone defects

• Applicant: Dr.-Ing. Corina Vater
• Subject Area: Biomaterials
• Term: from 2012 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 221326096

The surgical treatment of critical-size osseous defects that may arise from trauma, infection, degenerative diseases, tumor resection, periprosthetic bone loss, or congenital deformities is posed to be a special therapeutic challenge. Autologous bone grafting as the golden standard for the treatment of extended bone defects provides both bone precursor cells, growth factors, and a structural scaffold for site-specific bone regeneration. However, autologous bone grafting is associated with donor sitemorbidity (e.g., neurovascular injury, haematoma, fracture, and infection) in up to 30% of the patients and does not provide unlimited amounts of bone graft material (especially in older and/or patients with osteoporosis).To avoid donor site morbidity and due to the limited availability of bone autograft, the use of cancellous bone allografts (CBA) has become an alternative strategy. However, sterilized CBA lacks bone forming cells, growth factors and other organic structural components important for bone regeneration that leads to an increased rate of transplant failure caused by insufficient bony integration into the defect site. Functionalization with bioactive factors may enhance long-term osseointegration and improve the clinical performance of CBA. A natural source of bioactive factors is platelet rich plasma (PRP). PRP can be obtained from whole blood through various centrifugation steps and represents a fraction of plasma containing a 3- to 5-fold higher platelet concentration compared to untreated blood samples. By activating the platelets within the PRP a broad spectrum of growth factors, chemokines, amines, extracellular matrix proteins and nucleotides is released all of which can promote early bone regeneration. To achieve a controlled and sustained release of these bioactive factors PRP can be combined with different drug delivery systems.The aim of this project is to develop an optimal combination of 3D porous CBA with hydrogel based drug delivery systems releasing bioactive factors from PRP in a controlled and sustained manner. Therefore combinations of PRP and different commercially available and clinically approved hydrogels will be investigated concerning growth factor release kinetics, biocompatibility and chemotactic effects on bone marrow-derived cells. Depending on these results the optimal hydrogel incorporating PRP will be combined with 3D porous CBA to develop a homogeneously coated bioactive material.

• DFG Programme: Research Grants