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

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.

Bone morphogenetic protein 2‑enhanced osteogenic differentiation of stem cell spheres by regulation of Runx2 expression

“…The combined approach of osteoconductive scaffolds and osteoinductive growth factors may have synergistic effects on osteogenesis ( 17 ). In a previous report, the application of a combined approach with bone marrow mesenchymal stem cells, BMP-2 and hydroxyapatite led to successful treatment of critical-sized defects in human beings ( 18 ). Bone marrow stem cells were loaded into a hydrogel system by enzyme-catalyzed crosslinking, and the addition of bone BMP-2 led to the improvement of osteogenic potential ( 19 ).…”

Stem Cell Therapy in the Management of Fracture Non-Union – Evaluating Cellular Mechanisms and Clinical Progress

“…The first approach is considered a 'top-down' approach, whereby bioengineering focus is placed on optimising the extracellular environment to augment MSC differentiation down. Success has been demonstrated by including the combination of MSCs with hydroxyapatite (HA) granules and bone morphogenetic protein-2 (BMP-2), to promote osseointegration by utilising the biocompatibility and porosity of the added materials [32,38]. Dilogo et al appear to have demonstrated effective clinical results in promoting fracture healing and scaffold integration by utilising MSC and a 'top-down' approach in treating segmental bone defects in the non-union setting, utilising MSCs, HA granules and BMP-2 to facilitate both an osteogenic and osteoinductive environment [38].…”

“…The first approach is considered a ‘top-down’ approach, whereby bioengineering focus is placed on optimising the extracellular environment to augment MSC differentiation down. Success has been demonstrated by including the combination of MSCs with hydroxyapatite (HA) granules and bone morphogenetic protein-2 (BMP-2), to promote osseointegration by utilising the biocompatibility and porosity of the added materials [ 32 , 38 ]. Dilogo et al.…”

“…Dilogo et al. appear to have demonstrated effective clinical results in promoting fracture healing and scaffold integration by utilising MSC and a ‘top-down’ approach in treating segmental bone defects in the non-union setting, utilising MSCs, HA granules and BMP-2 to facilitate both an osteogenic and osteoinductive environment [ 38 ]. The ‘top-down’ approach can be considered the more well-validated tissue engineering technique in stem cell differentiation setting [ 37 ].…”

“…Significant clinical limitations exist relating to the long-term efficacy of MSCs in the treatment of non-union. Whilst a short-term positive clinical efficacy has been demonstrated by recent work, long-term 5-10 year follow-up of patients has not been evaluated within the current literature base [ 3 , 21 , 31 , 38 ]. Long-term follow-up analyses of current patient cohorts are needed to assess the anatomical and functional integrity of any bone repair, and whether any adverse effects of MSC use can be identified in the medium-to-long-term follow-up period.…”