Reconstruction of Bone Defect Combined with Massive Loss of Periosteum Using Injectable Human Mesenchymal Stem Cells in Biocompatible Ceramic Scaffolds in a Porcine Animal Model

Chun-Cheng Lin; Shih-Chieh Lin; Chao-Ching Chiang; Ming-Chau Chang; Oscar Kuang-Sheng Lee

doi:10.1155/2019/6832952

Reconstruction of Bone Defect Combined with Massive Loss of Periosteum Using Injectable Human Mesenchymal Stem Cells in Biocompatible Ceramic Scaffolds in a Porcine Animal Model

Stem Cells Int. 2019 Nov 23:2019:6832952. doi: 10.1155/2019/6832952. eCollection 2019.

Authors

Chun-Cheng Lin^{1

2}, Shih-Chieh Lin³, Chao-Ching Chiang^{2

4}, Ming-Chau Chang^{4

5}, Oscar Kuang-Sheng Lee^{1

6}

Affiliations

¹ Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
² Division of Orthopaedic Trauma, Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
³ Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
⁴ Department of Surgery, National Yang-Ming University, Taipei 11221, Taiwan.
⁵ Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
⁶ Department of Medical Research, Taipei Veterans General Hospital, Taipei 11217, Taiwan.

Abstract

Clinically, in patients who sustain severe open fractures, there is not only a segmental bone defect needed to be reconstructed but also insufficient healing capacity due to concomitant damages to the periosteum and surrounding soft tissues. For studying the reconstruction of bone defects associated with massive loss of periosteum and surrounding soft tissues, there are no well-established preclinical models in large animals in the literature. The purpose of the study was to generate a large animal model of bone defect with massive periosteum loss and to adopt a tissue engineering approach to achieve rapid bony union with stem cells and biomaterials. In this study, a bone defect with massive periosteum stripping was generated in pigs, which was followed by emptying nearby canal marrow including fat and cancellous bone. The stripped periosteum was a mimic to the situation in the Gustilo type 3 open fractures. Bone defects were then reconstructed by impacting the biocompatible ceramic scaffold, morselized tricalcium phosphate (TCP) loaded with human adipose tissue-derived mesenchymal stem cells (hMSCs). Radiological and pathological assessments indicated that TCP and hMSCs synergistically promoted bone healing with increased lamination and ingrowth of vessels. Both bridging periosteum formation and gap filling were induced rapidly. In conclusion, a porcine model of segmental bone loss with damage of surrounding periosteum was created. Reconstruction of such defects with hMSCs and TCP achieved rapid union of bone defects associated with massive periosteal stripping.