The present study proposed to conduct a systematic review research showing the isolated effects of PBMT by LLLT/LED (24–30) as well as the effects associated with synthetic biomaterials (31–42,49–50) where it was observed that in most studies, both the application of isolated PBMT and the use of PBMT associated with biomaterials allowed the stimulation of bone remodeling processes, in particular because of activities of multiplied deposition of hydroxyapatite and collagen synthesis withinside the osteoid matrix, in addition to preferred the development of biomechanical residences of bone, proliferation of the expression of genes and bone proteins, which inspired vascular proliferation (24–42).
In this review, results of studies investigating the isolated effects of PMBT on bone repair were presented. Tim et al. (24) evaluated bone formation, immunoexpression of osteogenic elements, and biomechanical houses in a rat tibial bone illness version after using PBMT. It turned into located that PBMT preferred bone restore through stimulating osteogenic elements in tibial lesions, however, no high-quality outcomes on biomechanical houses had been found; however, it's far of paramount significance to word that the outcomes approximately biomechanical parameters can be related to the experimental version, dosimetric parameters, and exceptional wavelengths used, considering research withinside the literature factor to the high-quality outcomes of PBMT on biomechanical variables (24).
Barbosa et al.(26) studied the process of bone regeneration through osteotomy in rats treated with PBMT per LLLT. It was proven that PBMT per LLLT was able to promote bone regeneration after 7 days of treatment at both wavelengths (660nm or 830nm), however, after 14 days of treatment, bone regeneration is more effective with PBMT per LLLT irradiation in the infrared electromagnetic spectrum (830nm). These results corroborate the findings proposed by Abramoff et al.27 who proved that PBMT per LLLT favored the increase of the newly formed bone area in the initial phase of the tibial repair process, when the animals were irradiated with PBMT per LLLT at infrared wavelength (808 nm). Both authors pointed out that PBMT favored promising results when applied during the proliferative and early differentiation stages of immature precursors, since it is believed that at this stage there is a stimulation of blood vascularization to increase the supply of circulating cells, nutrition, and oxygen, and thus stimulate bone repair (26–27).
Consolidating the results obtained by Tim et al. (24), Barbosa et al (26) and Abramoff et al. (27) about the isolated effects of PBMT per LLLT, Briteño-Vázquez et al. (28) investigated the bone healing of the fracture process in rats submitted to PBMT. It was found that PBMT (850 nm) promoted the process of bone healing and bone callus formation in rat tibiae, as well as increased fibroblast proliferation, bone matrix, and blood vessel neoformation.
The findings of these studies (24,26,27) can be reaffirmed by the study proposed by Sella et al. (29) who proved that PBMT in the infrared electromagnetic spectrum (808 nm) has satisfactory effects in all phases of scar repair, since its main purpose is to increase the expression of bone formation proteins and thus stimulate the bone remodeling phase. The results by applying PBMT by LLLT can be justified by the fact that irradiation in the near infrared electromagnetic spectrum (780 to 880 nm) within the specific optical window guarantees adequate penetration of the laser light into the biological tissue, since the absorption and scattering of the light (which depends on the wavelength and its maximum penetration), will provide optimal penetration into the biological tissue, thus favoring beneficial results (30).
Recently, several experimental studies have shown satisfactory results about the use of PBMT on bone repair. It is believed that the effects of the therapy are associated with the stimulation of osteoblasts, which in turn stimulate the production of bone matrix and, consequently, enable effects on mesenchymal cells. In general, PBMT acts on cytochrome IV (cytochrome-c-oxidase) and porphyrins, aiming to increase the cellular activity of adenosine triphosphate (ATP) in the mitochondrial crests (respiratory chain). This interaction favors calcium release and increases cellular differentiation of bone tissue, stimulating the migration of collagen production to the site of injury, promoting mineralization of the extracellular matrix, and thus accelerating the phases of bone repair, like inflammation, granulation tissue formation, bone callus formation, and bone remodeling (24–30).
Bone graft materials, regardless of their origin (autografts, allografts, alloplastic materials, or xenografts), have biological, physical, and chemical properties that help in the process of tissue repair, since there are materials that have osteointegration, osteoinduction, osteoconduction, and osteogenesis; however, only a material classified as autologous is able to trigger all four properties (43). The literature cites three simultaneous conditions as necessary in bone defect reconstruction: (I) osteoconductive properties; (II) inductive properties; and (III) the presence of bone forming cells. However, there are still gaps in the explanation of the mechanisms of PBMT associated with scaffolds; therefore, this systematic review also studied the effects of the associated treatment (PBMT and scaffolds) (43–44).
Fangel et al.(31) studied the isolated and associated effects between PMBT and a BS/PLGA bioactive material in the process of tibial bone repair in rats. The study showed that the association of treatments improved bone healing in tibial defects of osteoporotic rats (due to a greater deposition of new bone tissue and a significant increase in biomechanical properties). These findings were not reaffirmed by Pinto et al. (32), who demonstrated that the association between BS/PGLA and PBMT was not capable of stimulating the mechanical properties of the bone callus. The authors emphasized that the negative effects of the association between the treatment modalities were due to the dosimetry employed in the PBMT, since they did not stimulate bone healing.
The findings of Fangel et al. (31) are reaffirmed by Fernandes et al. (36) who proved that PBMT irradiation and the application of BS/PLGA increased osteoblast viability, accelerated material degradation and increased bone formation in a rat tibial bone defect, consequently, these data highlight the potential of the combination of BS/PLGA and PBMT as an effective tool in bone tissue engineering. The results of the BS/PLGA association culminate in increased cellular metabolism in osteoblasts, as the distinct nature of the findings for osteoblast and fibroblast cells may be due to a range of factors including cell line specificity, cell physiology, and/or cell line specificity when employed with appropriate dosimetric parameters within the near-infrared electromagnetic spectrum (31,36).
Titanium scaffolds induce self-regeneration of damaged bone tissue due to their high porosity, physical strength, biocompatibility, and osteoconductive properties, such as progenitor cells and growth factors, allowing the body to restore structure and functionality (45). Vasconcellos et al. (25) studied the effects of the association between PBMT and titanium implants in the process of bone healing in the femurs of osteopenic rats, and concluded that the action of PBMT minimizes the deleterious effects of experimental osteoporosis, especially in the initial phase of osseointegration of titanium implants, and increases bone formation in rats with regular bone metabolism. These findings corroborate the results found by Vasconcelos et al.(35) where the authors evaluated the effects of PBMT in the bone repair process in titanium scalffods in femurs of rats with osteoporosis and found that irradiated animals showed greater bone formation, favoring better osseointegration, These results may be justified by the use of PBMT, as this resource favors inflammation modulation, accelerates cell proliferation, improves bone repair, and promotes mesenchymal stem cell differentiation and osteoblastic differentiation (35–36).
Biological membranes had been used to save you the migration of lifeless tissue, forming bone defects, and had been indicated in aggregate with biomaterials and BMPs (37–42). Gerbi et al. (37) used Bone Morphogenetic Proteins (BMPs) withinside the bone restore manner, and the consequences discovered that the manage specimens had a predominance of medullary tissue withinside the cavity, at the same time as the experimental organizations confirmed a more quantity of neoformed bone tissue withinside the medullary and cortical cavity, agreeing with the histological consequences that confirmed accelerated capability for bone neoformation each with using BMPs in aggregate with bovine membrane and because of the impact of PBMT. These findings corroborate the observe proposed with the aid of using Rosso et al. (42) wherein the authors proved that PBMT, related to the biocomplex shaped with the aid of using Heterologous Fibrin Biopolymer (HFB) introduced to BM, has the ability to help withinside the manner of reconstruction of bone defects in rat tibiae.
The results found by Gerbi et al. (37) and Rosso et al. (42) can be justified because PBMT was employed with adequate dosimetry associated with adequate scaffolds, where both promoted satisfactory results on bone density, blood vessels, Havers canal development, as well as, it was seen that the procedure increases the differentiation and migration of bone tissue cells towards the irradiation site, resulting in increased collagen production and mineralization of the extracellular matrix. Reaffirming the explanation proposed by Gerbi et al. (37) and Rosso et al. (42), other researchers have also studied PBMT associated with collagen and elastin membranes derived from intestinal serosa (38), human demineralized bone structure (39), adipose tissue-derived stem cells (39), bioceramic cement (40), DBB bone graft (41) and HA/TCP biphasic ceramics (41) and all the studies proved that when these biomaterials were associated with PBMT they favored bone repair.
Despite the satisfactory results of the association between PBMT and biomaterials, it is also necessary to understand the evaluation methods to really reaffirm if all the findings are satisfactory in clinical practice, and among the most common diagnostic methods, Raman spectroscopy technique stands out47. Raman spectroscopy is an optical tool that allows less invasive and non-destructive analysis of biological samples, allowing to study information about their biochemical composition and monitor biological processes48. Soares et al. (33) and Soares et al. (34) studied bone mineralization by Raman spectroscopy evaluating Raman peak intensities of inorganic (∼960, ∼1,070 cm− 1) and organic (∼1,454 cm− 1) contents in an animal model. The authors proved that PBMT associated with biomaterials can effectively favor bone repair, however, it is necessary to emphasize that one should understand the mechanisms of action of the different types of biomaterials used, as well as, properly employ PBMT per LLLT and/or LED.
Gabbai Armelin et al (49). reported that the association of PBMT and Col to BG/Mg enabled a biostimulating effect of neovascularization due to the increase in the synthesis of angiogenic factors. Corroborating these findings, Pinheiro et al.(50) observed that MTA promotes an inflammatory response in the initial phase of repair at the end of 30 days. In relation to PBMT and MTA, it is possible to infer that the difference in hydroxyapatite disposition is probably due to the different parameters (of irradiation) used.
Corroborating the results found in this study, Gazor et al. (51) observed that the simultaneous use of hDBM + PBM of CSFD enabled an improvement in the bone healing process in rats. This improvement was probably caused by the increase in the osteoconductive potential of biomaterials promoted by PBMT.