Bone and cartilage regeneration
Sub-project: Bone regeneration – “Enhance bone regeneration with combined angiogenic and osteogenic factors in osteoporotic bone”
This project investigates 1) whether using cocultures of osteogenic cells and angiogenic factors with a composite can provide a live biomaterial; 2) if the composite can repair bone defect and enhance implant fixation in normal and osteoporotic sheep; and 3) in patients with osteoporosis via a randomized clinical trial.
Osteoporosis is a common aging-related disorder manifested clinically by skeletal fractures. Osteoporotic fractures have a complex pathogenesis involving both trauma to the bone and increased skeletal fragility. One of the most important side effects of long-term glucocorticoid therapy is secondary osteoporosis. It is estimated that up to 50% of the patients chronically treated with glucocorticoids will suffer fractures. These fractures are often difficult to stabilize because of fixation failure in weak osteoporotic bone. Therefore, problems such as orthopaedic implant loosening, delayed healing or non-union have been major postoperative concerns. The repair of large bone defects remains a major clinical challenge, particularly in osteoporotic (OP) patients.
The investigations will be performed in this project are (Figure 1)
Combined delivery of osteogenic and angiogenic factors is a novel approach in bone regenerative engineering. This project is designed to investigate whether using co-cultures of MSCs and VEGF into a biomaterial composite provides a live bone graft substitute; and whether this composite can repair bone defect and enhance implant fixation when implanted in vivo in both normal and osteoporotic sheep. It may hold great promise in regenerative medicine with success of this project.
The resemblance between bones from sheep and humans provides an unique model giving an insight into the cellular processes and defect repairs of bone remodeling and formation, which would be impossible to investigate in other models for preclinical settings. Finally, a randomized clinical trial is the most important assessment for the efficacy of this approach.
Study 1: To determine optimal dose and ratio of VEGF vs. MSCs in vivo in the bilateral sides of substitute transplantation s.c. in SCID mice. Study 2: To determine optimal dose and ratio of VEGF vs. MSCs in vivo in bilateral distal femoral implant-gap model in normal sheep. Study 3: To assess the efficacy of biomaterials with optimal VEGF/MSCs dose and ratio on early and medium-term implant fixation in OP sheep. Study 4: To evaluate the efficacy of biomaterials with optimal dose and ratio of osteogenic vs. angiogenic factors on implant fixation in OP patients with total hip replacement. Study 5: To measure biomarkers of bone turnover and angiogenesis in animals and in patients.
The methods used are micro-CT/nano-CT, mechanical test, histomorphometry, biomarkers, and Radio-Stereometric Analysis (RSA).
Available positions and Contacts
We always seek ambitious students (within medical or natural sciences) with a large degree of curiosity on nature’s biology. Contacts: Project “Bone regeneration” leader: Professor Ming Ding, email@example.com. WP 5 leaders: Professor Søren Overgaard firstname.lastname@example.org and professor Moustapha Kassem email@example.com
- Ding M, Danielsen CC, Overgaard S. The effects of glucocorticoid steroid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone. J Tissue Eng Regen Med 2012;6(6):443-50.
- Ding M, Røjskjær J, Cheng L, Theilgaard N, Overgaard S. The effects of a reinforced bone substitute and Colloss® E on bone healing in sheep. J Biomed Mater Res B Appl Biomater 2012 Oct;100B (7):1826-35.
- Zou, L., Luo, Y., Chen, M., Wang, G., Ding, M., Petersen, C. C., Kang, R., Dagnaes-Hansen, F., Zeng, Y., Lv, N., Ma, Q., Le, D. Q. S., Besenbacher, F., Bolund, L., Jensen, T. G., Kjems, J., Pu, W. T. & Bünger, C. A simple method for deriving functional MSCs and applied for osteogenesis in 3D scaffolds. Nature Publishing Group, Sci Rep. 2013 Jul 22;3:2243.
- Ding M, Andreasen CM, Dencker ML, Jensen AE, Theilgaard N, Overgaard S. Efficacy of a small cell-binding peptide coated hydroxyapatite substitute on bone formation and implant fixation in sheep. J Biomed Mater Res A. 2015 Apr;103(4):1357-65.
- Ding M, S.S Henriksen, D. Wendt, S. Overgaard. An automated perfusion bioreactor for the streamlined production of engineered osteogenic grafts. J Biomed Mater Res B Appl Biomater 2015 May 7. doi: 10.1002/jbm.b.33407
The Danish Council for Independent Research – Medical Sciences (DFF– 4004-00256, M Ding)”