Abstract

Current gold-standard strategies for bone regeneration do not achieve the optimal recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells—such as mesenchymal stem cells (MSCs)—and bioactive ceramic scaffolds—such as calcium phosphate-based (CaPs) bioceramics—seem promising. The biological properties of MSCs are influenced by the tissue source. This study aims to define the optimal MSC source and construct (i.e., the MSC–CaP combination) for clinical application in bone regeneration. A previous iTRAQ analysis generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow, and dental pulp, then cultured both on a plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate), to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) presented the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs demonstrated the greatest capacity to colonise the bioceramics. Furthermore, the results demonstrated a trend that DPSCs had the most robust increase in ALP activity. Regarding CaPs, β-tricalcium phosphate obtained the best viability results, while hydroxyapatite had the highest ALP activity values. Therefore, we propose DPSCs as suitable MSCs for cell-based bone regeneration strategies.

Highlights

  • Bone regeneration and bone remodelling can be considered two sides of the same coin

  • The anatomical localisation of the cells used is among those characteristics. This is the first comparative work that has analysed a possible osteogenic commitment depending on the anatomic localisation of non-commercial human mesenchymal stem cells (MSCs) from bone marrow, adipose tissue, and dental pulp seeded both on a plastic surface and calcium phosphate-based (CaPs) (β-TCP and HA)

  • FLNA, HSPA5/GRP78, and PALLD were up-regulated in subchondral bone, and their expression has been correlated with osteoblast differentiation, as they contribute to the stabilisation of cytoskeleton, which is necessary for the osteogenesis and regulation of protein folding and calcium flux [34,35,36,37]

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Summary

Introduction

Bone regeneration and bone remodelling can be considered two sides of the same coin. While bone remodelling is a life-long process, bone regeneration occurs mainly during bone healing [1]. For small fractures or injuries, the bone has an innate ability to repair without scarring [2]. These regenerative processes are largely surpassed by major bone damage, such as skeletal reconstruction surgeries, bone defects of various origins (e.g., traumatic, infectious, or tumoral), or congenital skeletal dysplasias. Current orthopaedic surgery strategies are mostly bone grafting (both autologous and allogeneic) and osteodistraction [3]. They can be combined with the use of growth factors or osteoinductive scaffolds.

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