Skip to main content
Top
Published in: International Orthopaedics 6/2019

Open Access 01-06-2019 | Bone Defect | Original Paper

Autologous mesenchymal stem cell implantation, hydroxyapatite, bone morphogenetic protein-2, and internal fixation for treating critical-sized defects: a translational study

Authors: Ismail Hadisoebroto Dilogo, Phedy Phedy, Erica Kholinne, Yoshi Pratama Djaja, Jessica Fiolin, Yuyus Kusnadi, Nyimas Diana Yulisa

Published in: International Orthopaedics | Issue 6/2019

Login to get access

Abstract

Introduction

Critical-sized defect (CSD) is one of the most challenging cases for orthopaedic surgeons. We aim to explore the therapeutic potential of the combination of bone marrow-derived mesenchymal stem cells (BM-MSCs), hydroxyapatite (HA) granules, bone morphogenetic protein-2 (BMP-2), and internal fixation for treating CSDs.

Methods

This was a translational study performed during the period of January 2012 to 2016. Subjects were patients diagnosed with CSDs who had previously failed surgical attempts. They were treated with the combination of autologous BM-MSCs, HA granules, BMP-2, and mechanical stabilization. Post-operative pain level, functional outcome, defect volume, and radiological healing were evaluated after a minimum follow-up of 12 months.

Results

A total of six subjects were recruited in this study. The pain was significantly reduced in all cases; with the decrease of mean preoperative visual analog scale (VAS) from 4 ± 2.2 to 0 after six month follow-up. Clinical functional outcome percentage increased significantly from 25 ± 13.7 to 70.79 ± 19.5. Radiological healing assessment using Tiedemann score also showed an increase from 0.16 ± 0.4 to 8 ± 3 at one year follow-up. No immunologic nor neoplastic side effects were found.

Conclusions

The combination of autologous BM-MSCs, HA granules, and BMP-2 is safe and remains to be a good option for the definitive treatment for CSD with previous failed surgical attempts. Further studies with a larger sample size are required to be done.
Literature
2.
go back to reference Li Y, Chen SK, Li L et al (2015) Bone defect animal models for testing efficacy of bone substitute biomaterials. J Orthop Transl 3:95–104 Li Y, Chen SK, Li L et al (2015) Bone defect animal models for testing efficacy of bone substitute biomaterials. J Orthop Transl 3:95–104
3.
go back to reference Mauffrey C, Barlow BT, Smith W (2015) Management of segmental bone defects. J Am Acad Orthop Surg 23:143–153 Mauffrey C, Barlow BT, Smith W (2015) Management of segmental bone defects. J Am Acad Orthop Surg 23:143–153
4.
10.
go back to reference Bucholz RW, Carlton A, Holmes R (1989) Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures. Clin Orthop Relat Res 240:53–62 Bucholz RW, Carlton A, Holmes R (1989) Interporous hydroxyapatite as a bone graft substitute in tibial plateau fractures. Clin Orthop Relat Res 240:53–62
15.
go back to reference Yaman F, Dundar S, Cakmak O et al (2017) Guided bone regeneration with polyethylene membrane, zoledronic acid and hydroxiapatide bone graft in peri-implant bone defect: an experimental study. Biomed Res 28:2684–2688 Yaman F, Dundar S, Cakmak O et al (2017) Guided bone regeneration with polyethylene membrane, zoledronic acid and hydroxiapatide bone graft in peri-implant bone defect: an experimental study. Biomed Res 28:2684–2688
21.
go back to reference Wang Y, Jiang H, Deng Z et al (2017) Comparison of monolateral external fixation and internal fixation for skeletal stabilisation in the management of small tibial bone defects following successful treatment of chronic osteomyelitis. Biomed Res Int. https://doi.org/10.1155/2017/6250635 Wang Y, Jiang H, Deng Z et al (2017) Comparison of monolateral external fixation and internal fixation for skeletal stabilisation in the management of small tibial bone defects following successful treatment of chronic osteomyelitis. Biomed Res Int. https://​doi.​org/​10.​1155/​2017/​6250635
23.
go back to reference Lubis AMT, Sandhow L, Lubis VK et al (2011) Isolation and cultivation of mesenchymal stem cells from iliac crest bone marrow for further cartilage defect management. Acta Med Indones 43:178–184PubMed Lubis AMT, Sandhow L, Lubis VK et al (2011) Isolation and cultivation of mesenchymal stem cells from iliac crest bone marrow for further cartilage defect management. Acta Med Indones 43:178–184PubMed
26.
go back to reference Tiedeman JJ, Lippiello L, Connolly JF, Strates BS (1990) Quantitative roentgenographic densitometry for assessing fracture healing. Acta Orthop Scand 61:128–130CrossRef Tiedeman JJ, Lippiello L, Connolly JF, Strates BS (1990) Quantitative roentgenographic densitometry for assessing fracture healing. Acta Orthop Scand 61:128–130CrossRef
33.
go back to reference Sulaiman SB, Keong TK, Cheng CH, Aminuddin Bin Saim RBHI (2013) Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone. Indian J Med Res 137:1093–1101PubMedPubMedCentral Sulaiman SB, Keong TK, Cheng CH, Aminuddin Bin Saim RBHI (2013) Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone. Indian J Med Res 137:1093–1101PubMedPubMedCentral
38.
go back to reference Sánchez F, Bolarm A, Molera P (2003) Relationship between particle size and manufacturing processing and sintered characteristics of iron powders. Rev Latin Met Mat 23:35–40 Sánchez F, Bolarm A, Molera P (2003) Relationship between particle size and manufacturing processing and sintered characteristics of iron powders. Rev Latin Met Mat 23:35–40
42.
go back to reference El Bialy I, Jiskoot W, Reza Nejadnik M (2017) Formulation, delivery and stability of bone morphogenetic proteins for effective bone regeneration. Pharm Res 34:1152–1170CrossRefPubMedPubMedCentral El Bialy I, Jiskoot W, Reza Nejadnik M (2017) Formulation, delivery and stability of bone morphogenetic proteins for effective bone regeneration. Pharm Res 34:1152–1170CrossRefPubMedPubMedCentral
Metadata
Title
Autologous mesenchymal stem cell implantation, hydroxyapatite, bone morphogenetic protein-2, and internal fixation for treating critical-sized defects: a translational study
Authors
Ismail Hadisoebroto Dilogo
Phedy Phedy
Erica Kholinne
Yoshi Pratama Djaja
Jessica Fiolin
Yuyus Kusnadi
Nyimas Diana Yulisa
Publication date
01-06-2019
Publisher
Springer Berlin Heidelberg
Keyword
Bone Defect
Published in
International Orthopaedics / Issue 6/2019
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-019-04307-z

Other articles of this Issue 6/2019

International Orthopaedics 6/2019 Go to the issue