title: Repair of bone defect using bone marrow cells and demineralized bone matrix supplemented with polymeric materials.
abstract: We present a novel, reverse thermo-responsive (RTR) polymeric osteogenic composite comprising demineralized bone matrix (DBM) and unmanipulated bone marrow cells (BMC) for repair of bone defects. The polymers investigated were low viscosity aqueous solutions at ambient temperature, which gel once they heat up and reach body temperature. Our goal to supplement DBM-BMC composite with RTR polymers displaying superior rheological properties, was to improve graft integrity and stability, during tissue regeneration. The osteogenic composite when implanted under kidney capsule of mice, proved to be biocompatible and biodegradable, with no residual polymer detected in the newly formed osteohematopoietic site. Implantation of the osteogenic composite into a large area of missing area of parietal bone of the skull of rats, resulted in an extensive remodeling of DBM particles, fully reconstituted hematopoietic microenvironment and well integrated normal flat bone within thirty days. The quality and shape of the newly created bone were comparable to the original bone and neither local or systemic inflammatory reactions nor fibrosis at the junction of the new and old calvarium could be documented. Furthermore, combined laser capture microdissection (LCM) technique and PCR analysis of male BMC in female rats confirmed the presence of male derived cells captured from the repaired/ regenerated flat bone defect. The use of active self sufficient osteogenic DBM-BMC composite supported by a viscous polymeric scaffold for purposive local hard tissue formation, may have a significant potential in enhancement of bone regeneration and repair following trauma, degenerative or inflamatory lesion, iatrogenic interventions and cosmetic indications.
authors.affiliation: Investigator-in-Charge, The international center for Cell Therapy & Cancer Immunotherapy, Top Ichilov at Weizman Center, Tel Aviv Medical Complex, 14 Weizman Street, Tel Aviv 64239, Israel.
authors.forename: Basan Gowda S
authors.initials: BG
authors.lastname: Kurkalli
authors.forename: Olga
authors.initials: O
authors.lastname: Gurevitch
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosnik
authors.forename: Daniel
authors.initials: D
authors.lastname: Cohn
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D018775:Bone Demineralization Technique; D001847:Bone Diseases / Q000473:pathology / Q000628:therapy*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D001857:Bone Matrix / Q000737:chemistry* / Q000637:transplantation; D001861:Bone Regeneration; D002478:Cells, Cultured; D005260:Female; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D011108:Polymers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D018183:Transplantation Chimera
chemical_list: D001672:Biocompatible Materials; D011108:Polymers