Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, Bologna, Italy.
Osteoarticolar Regeneration Laboratory, 3rd Orthopaedic and Traumatologic Clinic prevalently Oncologic, IRCCS Rizzoli Orthopaedic Institute, Bologna, Italy.
J Tissue Eng Regen Med. 2018 Sep;12(9):1972-1985. doi: 10.1002/term.2732. Epub 2018 Aug 16.
Nonunion treatment has a high rate of success, although recalcitrant nonunion may determine the need for amputation. Therefore, new treatment options are continuously investigated in order to further reduce the risk of nonunion recurrence. This study aimed to (a) develop a new large animal model for bone atrophic nonunion and (b) compare the efficacy of demineralized bone matrix (DBM) and DBM in combination with mesenchymal stem cells (MSC) in the new nonunion model. The new model consists of a noncritical, full-thickness segmental defect created in the sheep tibia, stabilized by an intramedullary nail, and involves the creation of a locally impaired blood supply achieved through periosteum excision and electrocauterization of the stump ends. Six weeks after defect creation, lack of hard tissue callus and established nonunion was observed in all operated tibiae both by radiographic and clinical evaluation. Nonunion was treated with allogeneic DBM or autologous MSC cultivated on DBM particles (DBM + MSC) for 1 day before implantation. Twelve weeks after treatment, radiographic, microtomographic, histologic, and histomorphometric analysis showed the formation of bone callus in DBM group, whereas the fracture healing appeared at an early stage in DBM + MSC group. Torsional strength and stiffness of the DBM group appeared higher than those of DBM + MSC group, although the differences were not statistically significant. In conclusion, a new sheep bone nonunion model resembling the complexity of the clinical condition was developed. DBM is an effective option for nonunion treatment, whereas MSC do not improve the healing process when cultivated on DBM particles before implantation.
非愈合治疗的成功率较高，尽管难治性不愈合可能需要截肢。因此，为了进一步降低非愈合复发的风险，不断探索新的治疗选择。本研究旨在：（a）建立一种新的大型动物萎缩性骨不连模型；（b）比较脱钙骨基质（DBM）和 DBM 联合间充质干细胞（MSC）在新不愈合模型中的疗效。新模型由绵羊胫骨中的非关键、全厚度节段性缺损组成，通过髓内钉稳定，并通过骨膜切除和残端电灼来实现局部受损的血液供应。在缺陷形成后 6 周，所有手术胫骨均通过放射学和临床评估观察到缺乏硬组织骨痂和已建立的不愈合。用同种异体 DBM 或在植入前用 DBM 颗粒培养的自体 MSC（DBM+MSC）治疗不愈合。治疗后 12 周，放射学、微断层扫描、组织学和组织形态计量学分析显示 DBM 组形成骨痂，而 DBM+MSC 组骨折愈合处于早期阶段。尽管差异无统计学意义，但 DBM 组的扭转强度和刚度似乎高于 DBM+MSC 组。总之，建立了一种新的绵羊骨不连模型，类似于临床情况的复杂性。DBM 是治疗不愈合的有效选择，而 MSC 在植入前在 DBM 颗粒上培养时并不能改善愈合过程。
