Evaluation of Human Bone Marrow Mesenchymal Stromal Cell (MSC) Functions on a Biomorphic Rattan-Wood-Derived Scaffold: A Comparison between Cultured and Uncultured MSCs.

Payal Ganguly,James Vun,Jehan J El-Jawhari,Peter V Giannoudis,Elena A Jones

doi:10.3390/bioengineering9010001

Abstract

The reconstruction of large bone defects requires the use of biocompatible osteoconductive scaffolds. These scaffolds are often loaded with the patient’s own bone marrow (BM) cells to facilitate osteoinductivity and biological potency. Scaffolds that are naturally sourced and fabricated through biomorphic transitions of rattan wood (B-HA scaffolds) offer a unique advantage of higher mechanical strength and bioactivity. In this study, we investigated the ability of a biomorphic B-HA scaffold (B-HA) to support the attachment, survival and gene expression profile of human uncultured BM-derived mesenchymal stromal cells (BMSCs, n = 6) and culture expanded MSCs (cMSCs, n = 7) in comparison to a sintered, porous HA scaffold (S-HA). B-HA scaffolds supported BMSC attachment (average 98%) and their survival up to 4 weeks in culture. Flow cytometry confirmed the phenotype of cMSCs on the scaffolds. Gene expression indicated clear segregation between cMSCs and BMSCs with MSC osteogenesis- and adipogenesis-related genes including RUNX2, PPARγ, ALP and FABP4 being higher expressed in BMSCs. These data indicated a unique transcriptional signature of BMSCs that was distinct from that of cMSCs regardless of the type of scaffold or time in culture. There was no statistical difference in the expression of osteogenic genes in BMSCs or cMSCs in B-HA compared to S-HA. VEGF release from cMSCs co-cultured with human endothelial cells (n = 4) on B-HA scaffolds suggested significantly higher supernatant concentration with endothelial cells on day 14. This indicated a potential mechanism for providing vasculature to the repair area when such scaffolds are used for treating large bone defects.

Highlights

Introduction iationsBone healing and repair following trauma remains a challenging physiological process, especially for patients who suffer from severe fracture injuries or have associated comorbidities such as obesity or diabetes
We provide evidence for mesenchymal stromal cells (MSCs) attachment, survival and gene expression of transcripts associated with multiple MSC functions including bone formation and angiogenesis support on biomorphic scaffolds (B-HAs)
The analysis revealed that B-HA scaffolds provided better BMSC attachment than S-HA; the differences were not statistically significant (Figure 2B(left))

Summary

Introduction

Introduction iationsBone healing and repair following trauma remains a challenging physiological process, especially for patients who suffer from severe fracture injuries or have associated comorbidities such as obesity or diabetes. The risk of an impaired healing response is higher in patients with osteoarthritis, who may need surgical treatments alongside drug intervention for enhanced osseointegration of the implants [1,2]. This impaired bone healing process often leads to a greater risk of fracture non-union, a complication that could require multiple surgical interventions with increased medical and societal costs [3]. The use of biomaterial scaffolds using the so-called ‘diamond concept’ has significantly improved the bone healing response and outcomes in such difficult clinical situations [4]. The concept involves the use of a platform/biomaterial that serves as the scaffold (matrix) onto which bone forming cells are added or can migrate to, under the Licensee MDPI, Basel, Switzerland.

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