Clinical trial NCT06150456: Study of Alveolar Bone Preservation Using Photobiomodulation Combined With Grafting With Scaffold Biomaterial
Official title: Evaluation of Alveolar Bone Preservation After Molar Extraction Using Photobiomodulation Combined With Grafting With Scaffold Biomaterial: Clinical, Randomized, Triple-blind Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Extracting Own Teeth
Bone Substitutes
Keywords: Bone regeneration
photobiomodulation
scaffold biomaterial
Lead sponsor: University of Nove de Julho
Sponsor class: OTHER
First posted: 2023-11-29
Enrollment: 60
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Bone graft added to the dental socket immediately after tooth extraction prevents atrophy and deformity of the bone at the site of element loss, enabling rehabilitation with implants. Photobiomodulation accelerates bone healing; stimulates blood flow; activates osteoblasts, decreases osteoclastic activity, and improves the integration of the biomaterial with bone tissue. The study aims to develop a protocol for the management and preservation of alveolar bone after the loss of first and/or second permanent molars in patients aged between 8 and 17 years, with an indication for extraction associated or not with 808 nm infrared laser treatment. . Materials and methods: 60 patients aged between 8 and 17 years will be randomized and randomly divided into 4 groups, n= 15: Exo (extraction), Exo+Laser (extraction and laser treatment), Exo+Biomat (extraction with graft biomaterial), Exo+Biomat+Laser (biomaterial extraction and grafting and laser treatment). The biomaterials of choice will be Plenum® OSShp and Plenum® Guide (Brazil), added to the alveolus immediately after molar extraction, groups that will receive the laser (λ = 808 nm, power = 100 mW, radiant energy 3J per point in 3 buccal, occlusal and lingual/palatal points), will receive the irradiation in the surgical act, 48 hours and 10 days after the surgery, in the Exo and Exo+Biomat groups a similar laser device without emission of irradiation will be used, the operator who will apply the laser and the patient will be blind to the device used and the patient will not know whether or not he received the biomaterial. Analysis: computed tomography and intraoral scanning were performed pre-surgery, 3 and 6 months after surgery; to assess bone volume by measuring the height and width of the socket in each group, as well as trabecular bone and the interdental space of the teeth lateral to the missing element. Statistical analysis will be performed using the Shapiro-Wilks test, Student's t-test, or Wilcoxon-Mann-Whitney test for parametric and non-parametric data, respectively, they will be two-tailed and the significance level adopted will be α = 0.05.

Detailed description: Clinical, randomized, triple-blind, triple-blind study (the patient will not know whether or not he has received the laser treatment or grafted with the biomaterial, and the operator who will apply the laser will also be blinded to the device with or without laser irradiation.

60 participants will be recruited to attend the dentistry clinic of Universidade Nove de Julho, in the courses of surgery, endodontics, and pediatric dentistry, as well as in a private office, with an indication for the removal of first and second upper and lower molars. This recruitment will only take place after approval by the ethics committee.

4.3 Sample size: The sample size was determined based on the primary outcome of the study: alveolar preservation with scaffold biomaterial. Based on data from Rosero et al. (Photobiomodulation as adjuvant therapy for alveolar preservation: a preliminary study in humans) and Araújo et al. (Ridge changes after engraftment of fresh extraction sockets in man. A randomized clinical trial) Our initial sample size estimate was 9 subjects per group for a significant level of 0.05 and an estimated test power of 80% for references 104 and 105. To account for the possible non-parametric distribution of the data, 15% more subjects should be added to each group. Another 25% will be added to account for possible dropouts, resulting in 13 participants per group and for greater safety and reliability, 15 patients were established in each group. G\*Power 3.1.9.6 was used to perform the calculations.

Materials used in the study:

The biomaterial chosen for this research is the Plenum® OSShp and Plenum® Guide (Brazil) allograft. They are completely synthetic bone grafts and resorbable regenerating membranes (free of animal and human origin).

Plenum® OSShp is a porous synthetic biphasic bioceramic (hydroxyapatite: β - tricalcium phosphate, HA: β-TCP - 70:30%), and the granules are 500 - 1000 µm.

Plenum® Guide is a polydioxanone (PDO)-based synthetic membrane material whose surface morphology closely mimics the extracellular matrix.

Randomization:

All participants will be invited to participate in the research and after signing the informed consent will be randomized into blocks of 4; 60 participants will be randomly divided into 4 groups n=15 Exo (extraction), Exo+Laser (extraction and treatment with 808 nm laser), Exo+Biomat (extraction with biomaterial graft), Exo+Biomat+Laser (extraction and grafting of biomaterial and 808 nm laser treatment). Participants will be randomly allocated by a computer-generated list (Excel) 4.7 CLINICAL PROCEDURE: At the pre-surgical moment, the patient will be submitted to a CT scan (Figure 12) and intraoral scanning (Figure 13) for initial measurement of the vertical and horizontal bone dimensions of the alveolus and between the adjacent teeth of the tooth to be extracted in position in the alveolus and dental arch, and surgical planning, as recommended by the best current dentistry practices, and will sign the Image Use Authorization Term (ANNEX 4). Pre-surgical guidance and delivery of prescriptions with the established drug protocol will also be carried out. All research patients will receive the same post-surgical guidance care (ANNEX 3) and the drug protocol performed for all tooth removal surgery with or without grafting with biomaterials. The tooth will be extracted using an odontosection technique to remove the roots with the least possible trauma. It will not be necessary to lift the soft tissue flap due to the properties of the membrane that will be used, reducing tissue trauma and helping to repair the surgical site. After the extraction, the biomaterial will be added and accommodated to the socket with instruments that allow this insertion and covered by a membrane that will serve as a mechanical barrier, preventing the invagination of the gingival tissue and the formation of keratinized tissue to close the surgical wound so as not to compromise the osseointegration of the bone biomaterial. grafted.

The Exo+Laser and Exo+Biomat+Laser groups will receive, in addition to the drug protocol and guidelines, laser treatment. The Exo and Exo+Biomat groups will use a similar laser device, however, it will not emit irradiation.

In the postoperative period at 3 and 6 months, new intraoral digital scanning and digital computed tomography exams will be performed to take images and perform volumetric analysis with specific software.

Eligibility criteria: Inclusion Criteria:

* All genders, aged between 8 and 17 years, without comorbidities, present satisfactory oral hygiene and present a condition of loss of first or second permanent molars

Exclusion Criteria:

* Habitual use of analgesic and anti-inflammatory medication for other comorbidities, present allergies to the proposed drug protocol, in neurological/psychiatric treatment, presence of teeth with lesions to be treated in the same hemiarch of the tooth to be removed, current smoking habit, pregnant or breast-feeding, presenting photosensitivity disorders, with the presence of neoplasia in the oral region; and patients with operative complications whose surgical time exceeds 90 minutes

Primary outcomes:
measure: Surgical intervention phase
timeFrame: Baseline, pre surgical, 3 and 6 months
Secondary outcomes:
measure: Interdental distance
timeFrame: Baseline, pre surgical, 3 and 6 months
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Universidade Nove de Julho
Study officials:
affiliation: University of Nove de Julho
name: Vanessa Dalapria
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schropp L, Wenzel A, Kostopoulos L, Karring T. Bone healing and soft tissue contour changes following single-tooth extraction: a clinical and radiographic 12-month prospective study. Int J Periodontics Restorative Dent. 2003 Aug;23(4):313-23.
citation: Petersen PE. The World Oral Health Report 2003: continuous improvement of oral health in the 21st century--the approach of the WHO Global Oral Health Programme. Community Dent Oral Epidemiol. 2003 Dec;31 Suppl 1:3-23. doi: 10.1046/j..2003.com122.x.
citation: De Marchi RJ, Hugo FN, Hilgert JB, Padilha DM. Association between oral health status and nutritional status in south Brazilian independent-living older people. Nutrition. 2008 Jun;24(6):546-53. doi: 10.1016/j.nut.2008.01.054.
citation: Rezaie M, Ghapanchi J, Haghnegahdar A, Khojastehpour L, Khorshidi H, Heidari H. A Radiographic Evaluation of Missing of Permanent First Molars in a Group of Iranian Children and Adults: A Retrospective Study. Int J Dent. 2018 Apr 1;2018:5253965. doi: 10.1155/2018/5253965. eCollection 2018.
citation: Saber AM, Altoukhi DH, Horaib MF, El-Housseiny AA, Alamoudi NM, Sabbagh HJ. Consequences of early extraction of compromised first permanent molar: a systematic review. BMC Oral Health. 2018 Apr 5;18(1):59. doi: 10.1186/s12903-018-0516-4.
citation: Alkhadra T. A Systematic Review of the Consequences of Early Extraction of First Permanent First Molar in Different Mixed Dentition Stages. J Int Soc Prev Community Dent. 2017 Sep-Oct;7(5):223-226. doi: 10.4103/jispcd.JISPCD_222_17. Epub 2017 Sep 18.
citation: Chappuis V, Araujo MG, Buser D. Clinical relevance of dimensional bone and soft tissue alterations post-extraction in esthetic sites. Periodontol 2000. 2017 Feb;73(1):73-83. doi: 10.1111/prd.12167.
citation: Barone A, Aldini NN, Fini M, Giardino R, Calvo Guirado JL, Covani U. Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study. J Periodontol. 2008 Aug;79(8):1370-7. doi: 10.1902/jop.2008.070628.
citation: Araujo MG, Lindhe J. Ridge preservation with the use of Bio-Oss collagen: A 6-month study in the dog. Clin Oral Implants Res. 2009 May;20(5):433-40. doi: 10.1111/j.1600-0501.2009.01705.x.
citation: Araujo MG, Sukekava F, Wennstrom JL, Lindhe J. Ridge alterations following implant placement in fresh extraction sockets: an experimental study in the dog. J Clin Periodontol. 2005 Jun;32(6):645-52. doi: 10.1111/j.1600-051X.2005.00726.x.
citation: Van der Weijden F, Dell'Acqua F, Slot DE. Alveolar bone dimensional changes of post-extraction sockets in humans: a systematic review. J Clin Periodontol. 2009 Dec;36(12):1048-58. doi: 10.1111/j.1600-051X.2009.01482.x.
citation: Osburn RC. Preservation of the alveolar ridge: a simplified technique for retaining teeth beneath removable appliances. J Indiana State Dent Assoc. 1974 Jan-Feb;53(1):8-11. No abstract available.
citation: PELTIER LF. The use of plaster of Paris to fill defects in bone. Clin Orthop. 1961;21:1-31. No abstract available.
citation: Artzi Z, Nemcovsky CE. The application of deproteinized bovine bone mineral for ridge preservation prior to implantation. Clinical and histological observations in a case report. J Periodontol. 1998 Sep;69(9):1062-7. doi: 10.1902/jop.1998.69.9.1062.
citation: Faour O, Dimitriou R, Cousins CA, Giannoudis PV. The use of bone graft substitutes in large cancellous voids: any specific needs? Injury. 2011 Sep;42 Suppl 2:S87-90. doi: 10.1016/j.injury.2011.06.020. Epub 2011 Jul 2.
citation: Misch CE, Perez HM. Atraumatic extractions: a biomechanical rationale. Dent Today. 2008 Aug;27(8):98, 100-1.
citation: Saito S, Shimizu N. Stimulatory effects of low-power laser irradiation on bone regeneration in midpalatal suture during expansion in the rat. Am J Orthod Dentofacial Orthop. 1997 May;111(5):525-32. doi: 10.1016/s0889-5406(97)70152-5.
citation: LeGeros RZ. Calcium phosphate materials in restorative dentistry: a review. Adv Dent Res. 1988 Aug;2(1):164-80. doi: 10.1177/08959374880020011101. No abstract available.
citation: Salama R, Burwell RD, Dickson IR. Recombined grafts of bone and marrow. The beneficial effect upon osteogenesis of impregnating xenograft (heterograft) bone with autologous red marrow. J Bone Joint Surg Br. 1973 May;55(2):402-17. No abstract available.
citation: Hoexter DL. Bone regeneration graft materials. J Oral Implantol. 2002;28(6):290-4. doi: 10.1563/1548-1336(2002)0282.3.CO;2.
citation: Landsberg CJ. Implementing socket seal surgery as a socket preservation technique for pontic site development: surgical steps revisited--a report of two cases. J Periodontol. 2008 May;79(5):945-54. doi: 10.1902/jop.2008.070298.
citation: Nemcovsky CE, Artzi Z, Moses O. Rotated palatal flap in immediate implant procedures. Clinical evaluation of 26 consecutive cases. Clin Oral Implants Res. 2000 Feb;11(1):83-90. doi: 10.1034/j.1600-0501.2000.011001083.x.
citation: Sclar AG. Strategies for management of single-tooth extraction sites in aesthetic implant therapy. J Oral Maxillofac Surg. 2004 Sep;62(9 Suppl 2):90-105. doi: 10.1016/j.joms.2004.06.041.
citation: Iasella JM, Greenwell H, Miller RL, Hill M, Drisko C, Bohra AA, Scheetz JP. Ridge preservation with freeze-dried bone allograft and a collagen membrane compared to extraction alone for implant site development: a clinical and histologic study in humans. J Periodontol. 2003 Jul;74(7):990-9. doi: 10.1902/jop.2003.74.7.990.
citation: Jung RE, Siegenthaler DW, Hammerle CH. Postextraction tissue management: a soft tissue punch technique. Int J Periodontics Restorative Dent. 2004 Dec;24(6):545-53.
citation: Davies N, Dobner S, Bezuidenhout D, Schmidt C, Beck M, Zisch AH, Zilla P. The dosage dependence of VEGF stimulation on scaffold neovascularisation. Biomaterials. 2008 Sep;29(26):3531-8. doi: 10.1016/j.biomaterials.2008.05.007. Epub 2008 Jun 9.
citation: Araujo MG, Lindhe J. Socket grafting with the use of autologous bone: an experimental study in the dog. Clin Oral Implants Res. 2011 Jan;22(1):9-13. doi: 10.1111/j.1600-0501.2010.01937.x. Epub 2010 Nov 22.
citation: Avila-Ortiz G, Elangovan S, Kramer KW, Blanchette D, Dawson DV. Effect of alveolar ridge preservation after tooth extraction: a systematic review and meta-analysis. J Dent Res. 2014 Oct;93(10):950-8. doi: 10.1177/0022034514541127. Epub 2014 Jun 25.
citation: Holtrop ME, Cox KA, Glowacki J. Cells of the mononuclear phagocytic system resorb implanted bone matrix: a histologic and ultrastructural study. Calcif Tissue Int. 1982 Sep;34(5):488-94. doi: 10.1007/BF02411290.
citation: Chappard D, Guillaume B, Mallet R, Pascaretti-Grizon F, Basle MF, Libouban H. Sinus lift augmentation and beta-TCP: a microCT and histologic analysis on human bone biopsies. Micron. 2010 Jun;41(4):321-6. doi: 10.1016/j.micron.2009.12.005. Epub 2009 Dec 22.
citation: Fickl S, Fischer K, Petersen N, Happe A, Schlee M, Schlagenhauf U, Kebschull M. Dimensional Evaluation of Different Ridge Preservation Techniques: A Randomized Clinical Study. Int J Periodontics Restorative Dent. 2017 May/Jun;37(3):403-410. doi: 10.11607/prd.2629.
citation: Artzi Z, Weinreb M, Givol N, Rohrer MD, Nemcovsky CE, Prasad HS, Tal H. Biomaterial resorption rate and healing site morphology of inorganic bovine bone and beta-tricalcium phosphate in the canine: a 24-month longitudinal histologic study and morphometric analysis. Int J Oral Maxillofac Implants. 2004 May-Jun;19(3):357-68.
citation: Pasqualini D, Cocero N, Castella A, Mela L, Bracco P. Primary and secondary closure of the surgical wound after removal of impacted mandibular third molars: a comparative study. Int J Oral Maxillofac Surg. 2005 Jan;34(1):52-7. doi: 10.1016/j.ijom.2004.01.023.
citation: Wood DL, Hoag PM, Donnenfeld OW, Rosenfeld LD. Alveolar crest reduction following full and partial thickness flaps. J Periodontol. 1972 Mar;43(3):141-4. doi: 10.1902/jop.1972.43.3.141. No abstract available.
citation: Ngeow WC, Lim D. Do Corticosteroids Still Have a Role in the Management of Third Molar Surgery? Adv Ther. 2016 Jul;33(7):1105-39. doi: 10.1007/s12325-016-0357-y. Epub 2016 Jun 10.
citation: Baxendale BR, Vater M, Lavery KM. Dexamethasone reduces pain and swelling following extraction of third molar teeth. Anaesthesia. 1993 Nov;48(11):961-4. doi: 10.1111/j.1365-2044.1993.tb07474.x.
citation: Tavares MG, Machado AP, Motta BG, Borsatto MC, Rosa AL, Xavier SP. Electro-acupuncture efficacy on pain control after mandibular third molar surgery. Braz Dent J. 2007;18(2):158-62. doi: 10.1590/s0103-64402007000200014.
citation: Seymour RA, Hawkesford JE, Weldon M, Brewster D. An evaluation of different ibuprofen preparations in the control of postoperative pain after third molar surgery. Br J Clin Pharmacol. 1991 Jan;31(1):83-7. doi: 10.1111/j.1365-2125.1991.tb03861.x.
citation: Merigo E, Vescovi P, Margalit M, Ricotti E, Stea S, Meleti M, Manfredi M, Fornaini C. Efficacy of LLLT in swelling and pain control after the extraction of lower impacted third molars. Laser Ther. 2015 Mar 31;24(1):39-46. doi: 10.5978/islsm.15-OR-05.
citation: Kathuria V, Dhillon JK, Kalra G. Low Level Laser Therapy: A Panacea for oral maladies. Laser Ther. 2015 Oct 2;24(3):215-23. doi: 10.5978/islsm.15-RA-01.
citation: Pandeshwar P, Roa MD, Das R, Shastry SP, Kaul R, Srinivasreddy MB. Photobiomodulation in oral medicine: a review. J Investig Clin Dent. 2016 May;7(2):114-26. doi: 10.1111/jicd.12148. Epub 2015 Feb 26.
citation: Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2012 Feb;40(2):516-33. doi: 10.1007/s10439-011-0454-7. Epub 2011 Nov 2.
citation: Rola P, Doroszko A, Derkacz A. The Use of Low-Level Energy Laser Radiation in Basic and Clinical Research. Adv Clin Exp Med. 2014 September-October;23(5):835-842. doi: 10.17219/acem/37263.
citation: Karu TI. [Molecular mechanism of the therapeutic effect of low-intensity laser irradiation]. Dokl Akad Nauk SSSR. 1986;291(5):1245-9. No abstract available. Russian.
citation: Basford JR. Low-energy laser therapy: controversies and new research findings. Lasers Surg Med. 1989;9(1):1-5. doi: 10.1002/lsm.1900090103. No abstract available.
citation: Basford JR. Low intensity laser therapy: still not an established clinical tool. Lasers Surg Med. 1995;16(4):331-42. doi: 10.1002/lsm.1900160404.
citation: Nicola JH, Nicola EM. Wavelength, frequency, and color: absolute or relative concepts? J Clin Laser Med Surg. 2002 Dec;20(6):307-11. doi: 10.1089/104454702320901080.
citation: AboElsaad NS, Soory M, Gadalla LM, Ragab LI, Dunne S, Zalata KR, Louca C. Effect of soft laser and bioactive glass on bone regeneration in the treatment of infra-bony defects (a clinical study). Lasers Med Sci. 2009 May;24(3):387-95. doi: 10.1007/s10103-008-0576-9. Epub 2008 Jun 26.
citation: Cavalcanti TM, Almeida-Barros RQ, Catao MH, Feitosa AP, Lins RD. Knowledge of the physical properties and interaction of laser with biological tissue in dentistry. An Bras Dermatol. 2011 Sep-Oct;86(5):955-60. doi: 10.1590/s0365-05962011000500014. English, Portuguese.
citation: Romao MM, Marques MM, Cortes AR, Horliana AC, Moreira MS, Lascala CA. Micro-computed tomography and histomorphometric analysis of human alveolar bone repair induced by laser phototherapy: a pilot study. Int J Oral Maxillofac Surg. 2015 Dec;44(12):1521-8. doi: 10.1016/j.ijom.2015.08.989. Epub 2015 Sep 14.
citation: Huang YY, Chen AC, Carroll JD, Hamblin MR. Biphasic dose response in low level light therapy. Dose Response. 2009 Sep 1;7(4):358-83. doi: 10.2203/dose-response.09-027.Hamblin.
citation: Karu TI, Kolyakov SF. Exact action spectra for cellular responses relevant to phototherapy. Photomed Laser Surg. 2005 Aug;23(4):355-61. doi: 10.1089/pho.2005.23.355.
citation: Casado PL, Duarte ME, Carvalho W, Esmeraldo da Silva L, Barboza EP. Ridge bone maintenance in human after extraction. Implant Dent. 2010 Aug;19(4):314-22. doi: 10.1097/ID.0b013e3181dec322.
citation: Liu X, Lyon R, Meier HT, Thometz J, Haworth ST. Effect of lower-level laser therapy on rabbit tibial fracture. Photomed Laser Surg. 2007 Dec;25(6):487-94. doi: 10.1089/pho.2006.2075.
citation: Renno AC, McDonnell PA, Parizotto NA, Laakso EL. The effects of laser irradiation on osteoblast and osteosarcoma cell proliferation and differentiation in vitro. Photomed Laser Surg. 2007 Aug;25(4):275-80. doi: 10.1089/pho.2007.2055.
citation: Silveira PC, Silva LA, Freitas TP, Latini A, Pinho RA. Effects of low-power laser irradiation (LPLI) at different wavelengths and doses on oxidative stress and fibrogenesis parameters in an animal model of wound healing. Lasers Med Sci. 2011 Jan;26(1):125-31. doi: 10.1007/s10103-010-0839-0. Epub 2010 Sep 24.
citation: Brignardello-Petersen R, Carrasco-Labra A, Araya I, Yanine N, Beyene J, Shah PS. Is adjuvant laser therapy effective for preventing pain, swelling, and trismus after surgical removal of impacted mandibular third molars? A systematic review and meta-analysis. J Oral Maxillofac Surg. 2012 Aug;70(8):1789-801. doi: 10.1016/j.joms.2012.01.008. Epub 2012 Mar 6.
citation: Kornman KS, Robertson PB. Fundamental principles affecting the outcomes of therapy for osseous lesions. Periodontol 2000. 2000 Feb;22:22-43. doi: 10.1034/j.1600-0757.2000.2220103.x. No abstract available.
citation: Pogrel MA, Chen JW, Zhang K. Effects of low-energy gallium-aluminum-arsenide laser irradiation on cultured fibroblasts and keratinocytes. Lasers Surg Med. 1997;20(4):426-32. doi: 10.1002/(sici)1096-9101(1997)20:43.0.co;2-s.
citation: Lirani-Galvao AP, Jorgetti V, da Silva OL. Comparative study of how low-level laser therapy and low-intensity pulsed ultrasound affect bone repair in rats. Photomed Laser Surg. 2006 Dec;24(6):735-40. doi: 10.1089/pho.2006.24.735.
citation: Barbos Pinheiro AL, Limeira Junior Fde A, Marquez Gerbi ME, Pedreira Ramalho LM, Marzola C, Carneiro Ponzi EA, Oliveira Soares A, Bandeira De Carvalho LC, Vieira Lima HC, Oliveira Goncalves T. Effect of 830-nm laser light on the repair of bone defects grafted with inorganic bovine bone and decalcified cortical osseous membrane. J Clin Laser Med Surg. 2003 Dec;21(6):383-8. doi: 10.1089/104454703322650202.
citation: Gerbi ME, Marques AM, Ramalho LM, Ponzi EA, Carvalho CM, Santos Rde C, Oliveira PC, Noia M, Pinheiro AL. Infrared laser light further improves bone healing when associated with bone morphogenic proteins: an in vivo study in a rodent model. Photomed Laser Surg. 2008 Feb;26(1):55-60. doi: 10.1089/pho.2007.2026.
citation: Lopes CB, Pacheco MT, Silveira L Jr, Duarte J, Cangussu MC, Pinheiro AL. The effect of the association of NIR laser therapy BMPs, and guided bone regeneration on tibial fractures treated with wire osteosynthesis: Raman spectroscopy study. J Photochem Photobiol B. 2007 Dec 14;89(2-3):125-30. doi: 10.1016/j.jphotobiol.2007.09.011. Epub 2007 Oct 1.
citation: Rochkind S, Kogan G, Luger EG, Salame K, Karp E, Graif M, Weiss J. Molecular structure of the bony tissue after experimental trauma to the mandibular region followed by laser therapy. Photomed Laser Surg. 2004 Jun;22(3):249-53. doi: 10.1089/1549541041438579.
citation: Coombe AR, Ho CT, Darendeliler MA, Hunter N, Philips JR, Chapple CC, Yum LW. The effects of low level laser irradiation on osteoblastic cells. Clin Orthod Res. 2001 Feb;4(1):3-14. doi: 10.1034/j.1600-0544.2001.040102.x.
citation: Ninomiya T, Miyamoto Y, Ito T, Yamashita A, Wakita M, Nishisaka T. High-intensity pulsed laser irradiation accelerates bone formation in metaphyseal trabecular bone in rat femur. J Bone Miner Metab. 2003;21(2):67-73. doi: 10.1007/s007740300011.
citation: Dalapria V, Marcos RL, Bussadori SK, Anselmo G, Benetti C, da Silva Santana ACA, Marinho NSR, Pinto RS, de Sales RS, de Franca LS, Deana AM. LED photobiomodulation therapy combined with biomaterial as a scaffold promotes better bone quality in the dental alveolus in an experimental extraction model. Lasers Med Sci. 2022 Apr;37(3):1583-1592. doi: 10.1007/s10103-021-03407-w. Epub 2021 Nov 12.
citation: Obradovic RR, Kesic LG, Pesevska S. Influence of low-level laser therapy on biomaterial osseointegration: a mini-review. Lasers Med Sci. 2009 May;24(3):447-51. doi: 10.1007/s10103-008-0573-z. Epub 2008 Jun 20.
citation: Rosero KAV, Sampaio RMF, Deboni MCZ, Correa L, Marques MM, Ferraz EP, da Graca Naclerio-Homem M. Photobiomodulation as an adjunctive therapy for alveolar socket preservation: a preliminary study in humans. Lasers Med Sci. 2020 Oct;35(8):1711-1720. doi: 10.1007/s10103-020-02962-y. Epub 2020 Jan 22.
citation: Araujo MG, da Silva JCC, de Mendonca AF, Lindhe J. Ridge alterations following grafting of fresh extraction sockets in man. A randomized clinical trial. Clin Oral Implants Res. 2015 Apr;26(4):407-412. doi: 10.1111/clr.12366. Epub 2014 Mar 12.