Bone marrow aspirate combined with low-level laser therapy: a new therapeutic approach to enhance bone healing.

This study evaluated the influence of bone marrow aspirate (BMA), low-level laser therapy (LLLT) and their combination on bone healing in surgically created critical-size defects (CSDs) in rat calvaria. 40 rats were divided into four groups: C (control), BMA, LLLT and BMA/LLLT. A 5mmdiameter CSD was created in the calvarium of each animal. In Group C, the defect was filled by blood clot only. In Group BMA, the defect was filled with BMA. In groups LLLT and BMA/LLLT, the defect received laser irradiation (InGaAlP laser), was filled with blood clot or BMA respectively, and irradiated again. Animals were euthanized 30 days postoperatively. Histomorphometric and immunohistochemical analyses were performed. Newly formed bone area (NFBA) was calculated as percentage of the total area of the original defect. Proliferating cell nuclear antigen (PCNA), runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) immunohistochemical staining were performed. PCNA-positive, Runx2-positive and OCN-positive cells were quantified. Data were statistically analyzed. Group BMA/LLLT had significantly greater NFBA than groups C, BMA or LLLT. Group BMA presented significantly greater NFBA than control, while group LLLT did not. Group BMA/LLLT presented a significantly higher number of PCNA-positive and OCN-positive cells than any of the other groups. Groups BMA/LLLT and BMA showed a significantly lower number of Runx2-positive cells than groups C or LLLT. The combination of BMA/LLLT yielded significantly greater bone formation in surgically created CSD in rat calvaria when compared to control, or either treatment alone.

[1]  S. Rosenwaks,et al.  Low level laser irradiation stimulates osteogenic phenotype of mesenchymal stem cells seeded on a three-dimensional biomatrix , 2005, Lasers in Medical Science.

[2]  F. Eduardo,et al.  Stem cell proliferation under low intensity laser irradiation: A preliminary study , 2008, Lasers in surgery and medicine.

[3]  Landulfo Silveira,et al.  The effect of the association of near infrared laser therapy, bone morphogenetic proteins, and guided bone regeneration on tibial fractures treated with internal rigid fixation: a Raman spectroscopic study. , 2010, Journal of biomedical materials research. Part A.

[4]  G. Duque.  Bone and fat connection in aging bone , 2008, Current opinion in rheumatology.

[5]  M D Gross,et al.  Effect of low intensity laser irradiation on surgically created bony defects in rats. , 2006, Journal of oral rehabilitation.

[6]  M. Pittenger,et al.  Human mesenchymal stem cells modulate allogeneic immune cell responses. , 2005, Blood.

[7]  A. Pinheiro,et al.  Photoengineering of bone repair processes. , 2006, Photomedicine and laser surgery.

[8]  Kwideok Park,et al.  Enhanced dermal wound neovascularization by targeted delivery of endothelial progenitor cells using an RGD-g-PLLA scaffold. , 2009, Biomaterials.

[9]  M. Marques,et al.  Irradiation at 780 nm increases proliferation rate of osteoblasts independently of dexamethasone presence , 2006, Lasers in surgery and medicine.

[10]  E. Zocchi,et al.  The association of human mesenchymal stem cells with BMP-7 improves bone regeneration of critical-size segmental bone defects in athymic rats. , 2010, Bone.

[11]  G. Clines.  Prospects for osteoprogenitor stem cells in fracture repair and osteoporosis , 2010, Current opinion in organ transplantation.

[12]  D. Smiler,et al.  A Histomorphogenic Analysis of Bone Grafts Augmented With Adult Stem Cells , 2007, Implant dentistry.

[13]  A. Etges,et al.  Effect of low-level laser therapy after implantation of poly-L-lactic/polyglycolic acid in the femurs of rats , 2009, Lasers in Medical Science.

[14]  H. Zhang,et al.  MicroRNA-193 pro-proliferation effects for bone mesenchymal stem cells after low-level laser irradiation treatment through inhibitor of growth family, member 5. , 2012, Stem cells and development.

[15]  H. Abrahamse,et al.  Low‐intensity laser irradiation at 660 nm stimulates cytochrome c oxidase in stressed fibroblast cells , 2012, Lasers in surgery and medicine.

[16]  S Saito,et al.  Stimulatory effects of low-power laser irradiation on bone regeneration in midpalatal suture during expansion in the rat. , 1997, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[17]  M A Trelles,et al.  Bone fracture consolidates faster with low‐power laser , 1987, Lasers in surgery and medicine.

[18]  S. Teoh,et al.  Superior Osteogenic Capacity for Bone Tissue Engineering of Fetal Compared with Perinatal and Adult Mesenchymal Stem Cells , 2009, Stem cells.

[19]  M. A. Leroux,et al.  Concise Review: Role of Mesenchymal Stem Cells in Wound Repair , 2012, Stem cells translational medicine.

[20]  Da Xing,et al.  Molecular mechanisms of cell proliferation induced by low power laser irradiation , 2009, Journal of Biomedical Science.

[21]  D. Xue,et al.  Reconstruction of rat calvarial defects with human mesenchymal stem cells and osteoblast-like cells in poly-lactic-co-glycolic acid scaffolds. , 2010, European cells & materials.

[22]  Jin‐Ho Choi,et al.  Transplantation of Endothelial Progenitor Cells Accelerates Dermal Wound Healing with Increased Recruitment of Monocytes/Macrophages and Neovascularization , 2005, Stem cells.

[23]  J. Seuntjens,et al.  Mesenchymal stem cell transplantation to promote bone healing , 2012, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[24]  A. Berghold,et al.  Influence of low-level laser treatment on bone regeneration and osseointegration of dental implants following sinus augmentation. An experimental study on sheep. , 2007, Clinical oral implants research.

[25]  K. Kraus,et al.  Mesenchymal stem cells and bone regeneration. , 2006, Veterinary surgery : VS.

[26]  W. Wiktor-Jedrzejczak,et al.  The use of bone-marrow-derived fibroblastoid cells and fresh bone marrow in the treatment of bone defects: an experimental study. , 1997, International journal of oral and maxillofacial surgery.

[27]  D. Kaigler,et al.  Angiogenic and osteogenic potential of bone repair cells for craniofacial regeneration. , 2010, Tissue engineering. Part A.

[28]  J. Macdermid,et al.  Effects of low power laser irradiation on bone healing in animals: a meta-analysis , 2010, Journal of orthopaedic surgery and research.

[29]  Y. Tokuhashi,et al.  Effects of Fibronectin on Osteoinductive Capability of Fresh Iliac Bone Marrow Aspirate in Posterolateral Spinal Fusion in Rabbits , 2008, Spine.

[30]  M. Giannelli,et al.  Photoactivation of bone marrow mesenchymal stromal cells with diode laser: Effects and mechanisms of action , 2013, Journal of cellular physiology.

[31]  M. Albitar,et al.  Toward the Identification of Mesenchymal Stem Cells in Bone Marrow and Peripheral Blood for Bone Regeneration , 2008, Implant dentistry.

[32]  Lydia Masako Ferreira,et al.  Effect of low-level laser therapy (GaAlAs) on bone regeneration in midpalatal anterior suture after surgically assisted rapid maxillary expansion. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[33]  P. A. McDonnell,et al.  The effects of laser irradiation on osteoblast and osteosarcoma cell proliferation and differentiation in vitro. , 2007, Photomedicine and laser surgery.

[34]  C. Padovani,et al.  Low-power laser irradiation improves histomorphometrical parameters and bone matrix organization during tibia wound healing in rats. , 2003, Journal of photochemistry and photobiology. B, Biology.

[35]  J. Marotti,et al.  Stability of dental implants after irradiation with an 830-nm low-level laser: a double-blind randomized clinical study , 2012, Lasers in Medical Science.

[36]  Gabi Drochioiu,et al.  Laser-induced ATP formation: mechanism and consequences. , 2010, Photomedicine and laser surgery.

[37]  Anthony Atala,et al.  Tissue engineering and regenerative medicine: concepts for clinical application. , 2004, Rejuvenation research.

[38]  M. Kurosaka,et al.  Therapeutic potential of vasculogenesis and osteogenesis promoted by peripheral blood CD34-positive cells for functional bone healing. , 2006, The American journal of pathology.

[39]  J. Greenberger,et al.  Bone marrow-derived stem cells and radiation response. , 2009, Seminars in radiation oncology.

[40]  H. Abrahamse,et al.  Irradiation at 830 nm stimulates nitric oxide production and inhibits pro‐inflammatory cytokines in diabetic wounded fibroblast cells , 2010, Lasers in surgery and medicine.

[41]  R. F. Rocha,et al.  Laser 904 nm action on bone repair in rats with osteoporosis , 2010, Osteoporosis International.

[42]  A. Hirata,et al.  Bone formation in a rat calvarial defect model after transplanting autogenous bone marrow with beta-tricalcium phosphate. , 2010, Acta histochemica.

[43]  R. Knuechel,et al.  The osteogenic differentiation of adult bone marrow and perinatal umbilical mesenchymal stem cells and matrix remodelling in three-dimensional collagen scaffolds. , 2010, Biomaterials.

[44]  F. Al-Watban,et al.  THE ACCELERATION OF WOUND HEALING IS NOT ATTRIBUTED TO LASER SKIN TRANSMISSION , 1999 .

[45]  M. Nagata,et al.  Influence of the proportion of particulate autogenous bone graft/platelet-rich plasma on bone healing in critical-size defects: an immunohistochemical analysis in rat calvaria. , 2009, Bone.

[46]  E. Mester,et al.  The biomedical effects of laser application , 1985, Lasers in surgery and medicine.

[47]  T. Deliberador,et al.  Bone healing in critical-size defects treated with platelet-rich plasma activated by two different methods. A histologic and histometric study in rat calvaria. , 2008, Journal of periodontal research.

[48]  I Garavello,et al.  The effects of low laser irradiation on angiogenesis in injured rat tibiae. , 2004, Histology and histopathology.

[49]  R. C. Dornelles,et al.  Bone healing in critical-size defects treated with platelet-rich plasma: a histologic and histometric study in rat calvaria. , 2008, Journal of periodontal research.

[50]  S. Sharma,et al.  Evaluation of hydroxyapatite and beta-tricalcium phosphate mixed with bone marrow aspirate as a bone graft substitute for posterolateral spinal fusion , 2009, Indian journal of orthopaedics.

[51]  D. Smiler,et al.  Bone Block Allograft Impregnated With Bone Marrow Aspirate , 2007, Implant dentistry.

[52]  A. Schindl,et al.  Low-intensity laser therapy: a review. , 2000, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[53]  R. Lizarelli,et al.  Effect of low‐level laser therapy on bone repair: Histological study in rats , 2007, Lasers in surgery and medicine.

[54]  H. Abrahamse,et al.  Influence of Low Intensity Laser Irradiation on Isolated Human Adipose Derived Stem Cells Over 72 Hours and Their Differentiation Potential into Smooth Muscle Cells Using Retinoic Acid , 2011, Stem Cell Reviews and Reports.

[55]  R. Khosravi,et al.  Cells from bone marrow that evolve into oral tissues and their clinical applications. , 2007, Oral diseases.

[56]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[57]  K. Mustafa,et al.  Effect of laser therapy on attachment, proliferation and differentiation of human osteoblast-like cells cultured on titanium implant material. , 2005, Biomaterials.