Evaluation of the effects of preconditioned human stem cells plus a scaffold and photobiomodulation administration on stereological parameters and gene expression levels in a critical size bone defect in rats.

We assessed the impact of photobiomodulation (PBM) plus adipose-derived stem cells (ASCs) during the anabolic and catabolic stages of bone healing in a rat model of a critical size femoral defect (CSFD) that was filled with a decellularized bone matrix (DBM). Stereological analysis and gene expression levels of bone morphogenetic protein 4 (BMP4), Runt-related transcription factor 2 (RUNX2), and stromal cell-derived factor 1 (SDF1) were determined. There were six groups of rats. Group 1 was the untreated control or DBM. Study groups 2-6 were treated as follows: ASC (ASC transplanted into DBM, then implanted in the CSFD); PBM (CSFD treated with PBM); irradiated ASC (iASC) (ASCs preconditioned with PBM, then transplanted into DBM, and implanted in the CSFD); ASC + PBM (ASCs transplanted into DBM, then implanted in the CSFD, followed by PBM administration); and iASC + PBM (the same as iASC, except CSFDs were exposed to PBM). At the anabolic step, all treatment groups had significantly increased trabecular bone volume (TBV) (24.22%) and osteoblasts (83.2%) compared to the control group (all, p = .000). However, TBV in group iASC + PBM groups were superior to the other groups (97.48% for osteoblast and 58.8% for trabecular bone volume) (all, p = .000). The numbers of osteocytes in ASC (78.2%) and iASC + PBM (30%) groups were remarkably higher compared to group control (both, p = .000). There were significantly higher SDF (1.5-fold), RUNX2 (1.3-fold), and BMP4 (1.9-fold) mRNA levels in the iASC + PBM group compared to the control and some of the treatment groups. At the catabolic step of bone healing, TBV increased significantly in PBM (30.77%), ASC + PBM (32.27%), and iASC + PBM (35.93%) groups compared to the control group (all, p = .000). There were significantly more osteoblasts and osteocytes in ASC (71.7%, 62.02%) (p = .002, p = .000); PBM (82.54%, 156%), iASC (179%, 23%), and ASC + PBM (108%, 110%) (all, p = .000), and iASC + PBM (79%, 100.6%) (p = .001, p = .000) groups compared to control group. ASC preconditioned with PBM in vitro plus PBM in vivo significantly increased stereological parameters and SDF1, RUNX2, and BMP4 mRNA expressions during bone healing in a CSFD model in rats.

Combined therapy of adipose-derived stem cells and photobiomodulation on accelerated bone healing of a critical size defect in an osteoporotic rat model.

We investigated the impact of human demineralized bone matrix (hDBM) plus adipose-derived stem cells (hADS) plus photobiomodulation (PBM) on a critical-sized femoral defect (CSFD) in ovariectomy induced osteoporosis in rats. There were 6 groups as follows. In group 1 (control, C), only CSFDs were created. Groups 2-6 were implanted with DBM into the CSFD (DBM-CSFD). In group 2 (S), only DBM was transplanted into the CSFD. In group 3 (S + PBM), the DBM-CSFDs were treated with PBM. In group 4, the DBM-CSFDs were treated with alendronate (S + ALN). In group 5, ADSs were seeded into DBM-CSFD (S + ADS). In group 6, ADSs were seeded into DBM-CSFD and the CSFDs were treated with PBM (S + PBM + ADS). At week eight (catabolic phase of bone repair), the S + ALN, S + PBM + ADS, S + PBM, and S + ADS groups all had significantly increased bone strength than the S group (ANOVA, p = 0.000). The S + PBM, S + PBM + ADS, and S + ADS groups had significantly increased Hounsfield unit than the S group (ANOVA, p = 0.000). ALN, ADS, and PBM significantly increased healed bone strength in an experimental model of DBM-treated CSFD in the catabolic phase of bone healing in osteoporotic rats. However, ALN alone and PBM plus ADS were superior to the other protocols.

Preconditioning adipose-derived stem cells with photobiomodulation significantly increased bone healing in a critical size femoral defect in rats.

We assessed the combined impacts of human demineralized bone matrix (hDBM) scaffold, adipose-derived stem cells (hADS), and photobiomodulation (PBM) on bone repair of a critical size femoral defect (CSFD) in 72 rats. The rats were divided into six groups: control (group 1); ADS (group 2 - ADS transplanted into hDBM); PBM (group 3 - PBM-treated CSFDs); ADS + PBM in vivo (group 4 - ADS transplanted into hDBM and the CSFDs were treated with PBM in vivo); ADS + PBM in vitro (group 5 - ADS were treated with PBM in vitro, then seeded into hDBM); and ADS + PBM in vitro+in vivo (group 6 - PBM-treated ADS were seeded into hDBM, and the CSFDs were treated with PBM in vivo. At the anabolic phase (2 weeks after surgery), bone strength parameters of the groups 5, 6, and 4 were statistically greater than the control, ADS, and PBM in vivo groups (all, p = 0.000). Computed tomography (CT) scans during the catabolic phase (6 weeks after surgery) of bone healing revealed that the Hounsfield unit (HU) of CSFD in the groups 2 (p = 0.000) and 5 (p = 0.019) groups were statistically greater than the control group. The groups 5, 4, and 6 had significantly increased bone strength parameters compared with the PBM in vivo, control, and ADS groups (all, p = 0.000). The group 5 was statistically better than the groups 4, and 6 (both, p = 0.000). In vitro preconditioned of hADS with PBM significantly increased bone repair in a rat model of CSFD in vivo.