Low power laser irradiation and human adipose-derived stem cell treatments promote bone regeneration in critical-sized calvarial defects in rats.

Yan-Hsiung Wang,Mei-Ling Ho,Chia-Hsin Chen,Min-Hsuan Chiang,Gianpaolo Papaccio,Ming-Long Yeh,Jyun-Yi Wu,Su Chii Kong

doi:10.1371/journal.pone.0195337

Abstract

Both stem cell therapy and physical treatments have been shown to be beneficial in accelerating bone healing. However, the efficacy of combined treatment with stem cells and physical stimuli for large bone defects remains uncertain. The aim of this study was to evaluate the bone regeneration effects of low-power laser irradiation (LPLI) and human adipose-derived stem cell (ADSC) treatments during fracture repair using a comparative rat calvarial defect model. We evaluated the viability of human ADSCs, which were cultured on a porous PLGA scaffold using an MTS assay. The critical-sized calvarial bone defect rats were divided into 4 groups: control group, LPLI group, ADSC group, and ADSC+LPLI group. Bone formation was evaluated using micro-CT. New bone formation areas and osteogenic factor expression levels were then examined by histomorphological analysis and immunohistochemical staining. Our data showed that PLGA had no cytotoxic effect on human ADSCs. Micro-CT analyses revealed that both the LPLI and ADSC groups showed improved calvarial bone defect healing compared to the control group. In addition, the ADSC+LPLI group showed significantly increased bone volume at 16 weeks after surgery. The area of new bone formation ranked as follows: control group < LPLI group < ADSC group < ADSC+LPLI group. There were significant differences between the groups. In addition, both ADSC and ADSC+LPLI groups showed strong signals of vWF expression. ADSC and LPLI treatments improved fracture repair in critical-sized calvarial defects in rats. Importantly, the combined treatment of ADSCs and LPLI further enhances the bone healing process.

Highlights

Critical-sized bone defects are formed when the bone loses its intrinsic capacity to spontaneously heal, leading to extensive bone loss; once such defects occur, external interventions are necessary for healing to progress [1]
The results showed that most adiposederived stem cell (ADSC) were viable in the scaffold compared to the control group, indicating that seeding ADSCs onto the scaffold did not affect their viability; poly-lactic-co-glycolic acid (PLGA) is likely not toxic to the cells (Fig 2D)
Our present findings highlight the effects of the ADSC and/or low-power laser irradiation (LPLI) treatments on stimulating bone tissue regeneration and inducing bone fracture healing

Summary

Introduction

Critical-sized bone defects are formed when the bone loses its intrinsic capacity to spontaneously heal, leading to extensive bone loss; once such defects occur, external interventions are necessary for healing to progress [1]. These large bone defects often arise following trauma, non-union, debridement of infections, resection of tumors or periprosthetic osteolysis [2]. The resources of bone grafts, which are commonly used in the treatment of critical-sized bone defects, can be generated by autologous, homologous, and heterologous methods These resources are often accompanied by various limitations and challenging post-operative complications, such as disease transmission and immunologic reactions. ADSCs are a superior cell to other types of adult stem cells as a source for clinical approaches

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