Imagine if craniomaxillofacial bone defects could be reconstructed using autogenous bone grafts that match, exactly, the defect?
Here’s what’s going on at the Indiana University School of Dentistry:
Principal investigator Tien-Min G. Chu* and his research team are developing such a graft using stem cells and platelet precursors (megakaryocytes) embedded in a three-dimensional scaffold composed of thrombopoeitin hydrogel matrix for reconstruction of cranial bone defects.
Dr. Chu’s hypothesis, building on prior studies of the interactions between megakaryocytes (MK), thrombopoietin (TPO) and osteoblasts (OB), is that TPO released from thiol-acrylate hydrogel on a 3D scaffold can promote bone regeneration in critical-size cranial defects, and that the use of stem cells will further enhance regeneration.
According to his OMS Foundation Research Support Grant Interim Progress Report, principle investigator Tien-Min G. Chu* is studying three dimensional scaffolds of thrombopoietin- laced hydrogels embedded with stem cells and platelet precursors (MK’s) for cranial bone regeneration.
Their bench top studies looking at the degradation rates of various hydrogels determined the optimal gel polymer concentration supporting survival of pre-osteoblast cells (MC3T3) encapsulated in the thiol-based hydrogel to be 5%. The group is confirming these results using bone marrow derived stem cells (BMSC) and dental pulp derived stem cells (DPSC). So far, in these studies the 5% gel concentration also supports the highest cell survival. Since TPO is the main growth factor for MKs, Chu expected TPO to affect BMSC and DPSC indirectly through MK co- cultured in the gel medium. When the group evaluated the effects of megakaryocyte (MK) co-culture on the proliferation and differentiation of BMSC and DPSC, their results showed that MK co-culture significantly increases BMSC and DPSC proliferation, regardless of the medium type, but that the MK co-culture delayed BMSC and DPSC differentiation. This is consistent with their preliminary in vivo observation of TPO enhanced bone regeneration in rat femoral segmental defect model.
Their research is now being conducted in vivo to evaluate the effect of culture medium, cell type, and gel concentration on in vivo cranial regeneration through stem cells encapsulated in thio-based hydrogels. Four non-critical sized cranial defects of 5 mm in diameter were created in the cranium of four 2.5 kg New Zealand white rabbits. A total of 16 defects were created. Eight groups of samples were fabricated with two samples per group. 200,000 cells were encapsulated in each sample. The samples were implanted on November 10th and 11th and retrieved on December 21st after six weeks of implantation.
The retrieved samples are being analyzed using histology, dynamic histomorphometry and micro-CT. The results from this pilot study will be evaluated and a full scale study with sample size capable of providing statistic power will be conducted this month. The combination of cell type, gel concentration and culture medium that yields the highest amount of bone formation will further research and development. The overall goal is to translate this research into human clinical applications. Dr. Chu anticipates completing the project at the end of 2016.
Based on the preliminary data, four abstracts submitted by Dr. Chu and his research team to two professional conferences with acknowledgment of OMS Foundation support have been accepted.
- Annual Meeting of American Association of Dental Research (March 15- 19, 2016, in Los Angeles, CA)
- Blake Ballenger, Alarbi Emmakah, Chien-Chi Lin, Tien-Min Gabriel Chu, Degradation and Cell Proliferation in a Fast-Degrading Thio-Acrylate based Hydrogel for Cranial Regeneration
- Alarbi Emmakah, Yinghua Cheng, Marta B Alvare, Melissa Ann Kacena, Tien-Min Gabriel Chu, Proliferation and Differentiation of Stem Cells Co-Cultured with Megakaryocytes
- Biomaterial World Congress (May 18 to 21, 2016, Montreal, Canada)
- Alarbi Emmakah, Yinghua Cheng, Marta B Alvare, Melissa Ann Kacena, Tien-Min Gabriel Chu, Megakaryocytes Enhances Proliferation but Delayed Differentiation in Stem Cells
- Alarbi Emmakah, Chien-Chi Lin, Tien-Min Gabriel Chu, Degradation and Cell Proliferation in a Fast-Degrading Thio-Acrylate Based Hydrogel for Cranial Regeneration
*(2014 Applicant, Funded by OMS Foundation in 2015, No Cost Extension approved to 12/31/2016)