Tissue engineering in bone defects: Development of porous copolymer scaffolds stimulating stem cell growth and bone regeneration
Development of a novel scaffold for bone repair
Bone defects due to ablative surgery, injuries and to pathological and physiological bone resorption still represent a major challenge. For mesenchymal stem cells-directed bone repair to be clinically successful, a scaffold must be identified and optimized. Our main goal is to synthesis a novel and a well-defined resorbable polymer scaffold.
The main goals of this research then are to synthesize a novel and well-defined resorbable scaffold effective for vascular reconstruction and bone and cartilage regeneration and to investigate the potential of the developed materials (scaffold) to grow bone mesenchymal stem cells (MSC) according to the concept of tissue engineering and to set up an optimal protocol to isolate and differentiate MSC within the substrate. To develop the second generation of bioresorabable copolymers which is aimed to result from this project, scaffolds are prepared by copolymerization of the commonly used L-lactide (LLA) polymer and the completely amorphous polymer 1,5-dioxepan-2-one (DXO-CO-LLA) or with trimethylene carbonate (TMC-CO-LLA) or with caprolactone (CL-CO-LLA) as monamers. Our hypothesis was based on the molecular modifications of the resorbable polymer systems which might stimulate specific interactions with cell integrins and thereby direct cell adhesion, proliferation, differentiation and extracellular matrix production and organization, cellular phenotype and gene expression profile.
To achieve the goals, the research program has been divided into 3 sub-projects as:
Sub-project I: Synthesis of a novel and well-defined resorbable polymers: Incipient analyses of mesenchymal stem cells.
Sub-project II: Effect of copolymers scaffolds on gene and protein expression profile using combined mesenchymal stem cell culture and experimental animal studies.
Sub-project III: Expression, recognition and usage of extracellular matrix proteins immobilized on copolymer scaffolds by mesenchymal stem cells and osteoblasts.
Summary of preliminary results:
MSCs and endothelial cells are cultured on various copolymer scaffolds and a series of in vitro and in vivo studies are performed to characterize the material. The in vivo experiments are performed aiming to evaluate the degradation of the material, the adherence and osteogenic potential of the expanded MSCs on the copolymers and to investigate the potential of the newly developed copolymers to repair bone defects utilizing the principles of tissue engineering. After in vivo studies in animal models, prospective studies on humans must eventually be undertaken. Within the forthcoming 5 - 10 years this project will be in a limited well structured ethical approved clinical phase. The criteria for inclusion and exclusion and the treatment will follow a strict protocol.
The project initiated recently and the preliminary results have been presented in the Norwegian Stem Cell Networking Meeting, 18 – 19, October 2007, Oslo, in two international conferences and 10 manuscripts are under preparation. In this project, 6 PhD students are currently involved. The students together, are working in close collaboration with each other within an established net work of closely integrated national partners at UIB, and international partners.
Our preliminary findings showed that the developed scaffolds retained good mechanical properties and high elasticity with controlled tensile properties and hydrophilicity during several weeks of degradation. Furthermore, the material can be optimized according to required application.
The promoted cell growth on the porous scaffolds synthesized by polymerization of various combinations of DXO, LLA, and CL indicated that the developed materials might be suitable as scaffolds for tissue engineering. So far better cell growth and differentiation have been observed on the scaffolds with the larger pore sizes.
Using optical tweezers for measuring the interaction forces between human bone cells and implant surfaces: System design and force calibration.
Rev Sci Instrum 2007 Jul;78(7):074302.
Development of Biodegradable Scaffolds Stimulating Fibroblast Attachment and Growth
J Dent Res 2007, Abstract 2187; IADR Meeting 2007, New Orleans, USA.
Hellem E, Arvidson K, Tornes K, Wistrand A, Albertsson AC, Bolstad AI, Mustafa K
J Dent Res 2007, Abstract 2186; IADR Meeting 2007, New Orleans, USA.