Abstract

Therapies using human mesenchymal stem cells (MSCs) combined with three-dimensional (3D) printed scaffolds are a promising strategy for bone grafting. But the harvest of MSCs still remains invasive for patients. Human synovial fluid MSCs (hSF-MSCs), which can be obtained by a minimally invasive needle-aspiration procedure, have been used for cartilage repair. However, little is known of hSF-MSCs in bone regeneration. Polyetherketoneketone (PEKK) is an attractive bone scaffold due to its mechanical properties comparable to bone. In this study, 3D-printed PEKK scaffolds were fabricated using laser sintering technique. hSF-MSCs were characterized and cultured on PEKK to evaluate their cell attachment, proliferation, and osteogenic potential. Rabbit calvarial critical-sized bone defects were created to test the bone regenerative effect of PEKK with hSF-MSCs. In vitro results showed that hSF-MSCs attached, proliferated, and were osteogenic on PEKK. In vivo results indicated that PEKK seeded with hSF-MSCs regenerated twice the amount of newly formed bone when compared to PEKK seeded with osteogenically-induced hSF-MSCs or PEKK scaffolds alone. These results suggested that there was no need to induce hSF-MSCs into osteoblasts prior to their transplantations in vivo. In conclusion, the combined use of PEKK and hSF-MSCs was effective in regenerating critical-sized bone defects.

Highlights

  • Each year, there are 2.2 million bone grafting procedures performed worldwide in numerous medical disciplines including in orthopedics and in dentistry[1]

  • Our previous studies indicated that hSF-Mesenchymal Stem Cells (MSCs) could be collected from the synovial fluid of the temporomandibular joint (TMJ) in patients with temporomandibular disorders (TMD)34. hSF-MSCs were found to be multipotent, with a greater capacity for chondrogenesis; these cells were suggested to be best used for cartilage repair[24,26,35]

  • Characteristics of hSF-MSCs. hSF-MSCs derived from five donors were used in this study. hSF-MSCs at cell passage 3 were assessed for their multilineage differentiation characteristics, according to the guidelines of the International Society of Cellular Therapy (ISCT)

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Summary

Introduction

There are 2.2 million bone grafting procedures performed worldwide in numerous medical disciplines including in orthopedics and in dentistry[1]. HSF-MSCs were demonstrated to possess a greater osteogenic potential than MSCs from many other tissue sources[35], their applications for bone regeneration have been barely investigated in the literature. This study aims to examine the bone regeneration capacity of hSF-MSCs. Bone tissue engineering requires a three-dimensional (3D) biomaterial/scaffold to reconstruct osseous defects and to support the survival of the transplanted cells. Polyetherketoneketone (PEKK) has recently been demonstrated as an adequate 3D scaffold for bone tissue engineering due to its biocompatibility, biomechanical properties, and ease in prognostic evaluation (radiolucency) once transplanted in vivo[36,37,38,39]. This study aimed to investigate further the in vivo osteogenic capability of hSF-MSCs when combined to 3D-printed PEKK scaffolds. We hypothesized that combining hSF-MSCs to PEKK scaffolds would enhance new bone formation in vivo in an established rabbit calvarial critical-sized defect (CSD). To the best of our knowledge, this is the first study in its kind

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