Journal of Dental Implants
   About JDI | Editorial | Search | Ahead of print | Current Issue | Archives | Instructions | Subscribe | Login 
Users Online: 697  Wide layoutNarrow layoutFull screen layout Home Print this page  Email this page Small font size Default font size Increase font size


 
 
Table of Contents
REVIEW ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 1  |  Page : 13-22

Bone regeneration associated with low-level laser therapy in implantology


1 Departments of Surgery and Oral Pathology, Arnaldo Jansen Dentistry Faculty, Federal University of Minas Gerais, Minas Gerais, Brazil
2 Departments of Surgery and Oral Pathology, Dentistry Faculty, Federal University of Minas Gerais, Minas Gerais, Brazil
3 Department of Surgery, Núcleo Postgraduation School, Federal University of Minas Gerais, Minas Gerais, Brazil
4 Department of Mechanical Engineering, Federal University of Minas Gerais, Minas Gerais, Brazil
5 Departments of Surgery and Oral Pathology, Federal University of Minas Gerais, Dentistry Faculty, Minas Gerais, Brazil
6 Departments of Restorative Dentistry and Dental Materials and Prosthodontics, Dentistry Faculty, Federal University of Minas Gerais, Minas Gerais, Brazil

Date of Submission26-Mar-2020
Date of Acceptance21-Oct-2020
Date of Web Publication10-Jun-2021

Correspondence Address:
Dr. Karina I R Teixeira
Faculdade Arnaldo Jansen, Vitório Marçola Street, 360-Anchieta, Belo Horizonte
Brazil
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdi.jdi_6_20

Rights and Permissions
   Abstract 

Several therapies for tissue regeneration in implantology have been explored for their ability to enhance bone regeneration such as low-level laser therapy (LLLT), also known as photobiomodulation. This technique has been shown to reduce inflammation and edema, induce analgesia, and promote healing in a range of musculoskeletal pathologies with cost-effective for healing therapy. The endothelial progenitor and hematopoietic stem cells, together with LLLT improving their capacity to induce angiogenesis, recruit other cells to a site of injury and secrete growth factors and cytokines that have a paracrine effect on surrounding cells. A critical review and comprehensively analyze of tissue regeneration associated to newer regenerative techniques as LLLT, platelet derivatives and mesenchymal stem cells (MSCs) at preimplant sites was released. An electronic search in PubMed via Medline and Embase was conducted of publications from the previous 10 years. English language articles related to the subject were found using selected keywords. We summarize the photobiomodulation properties and its relation with platelet derivatives and MSCs and discuss the efficacy of these therapies for tissue repair. The LLLT is well-documented therapy but further research studies relating LLLT to tissue regeneration in periodontics and implantology are needed.

Keywords: Low-level laser therapy, mesenchymal cells, peri-implant tissue, platelet derivatives, tissue regeneration


How to cite this article:
R Teixeira KI, Mendonca JA, Rosa MB, Huebner R, Cortés ME, L Ferreira MV. Bone regeneration associated with low-level laser therapy in implantology. J Dent Implant 2021;11:13-22

How to cite this URL:
R Teixeira KI, Mendonca JA, Rosa MB, Huebner R, Cortés ME, L Ferreira MV. Bone regeneration associated with low-level laser therapy in implantology. J Dent Implant [serial online] 2021 [cited 2021 Sep 25];11:13-22. Available from: https://www.jdionline.org/text.asp?2021/11/1/13/318072




   Introduction Top


Bone is a dynamic specialized and highly organized biological tissue that consists of organic and inorganic components.[1] Osseous tissue of cortical bone and cancellous bone is biochemically identical but structurally distinct. It consists of an organic phase of main collagen fibers, which impart strength, flexibility, and resistance to torsional force, and an inorganic phase of main hydroxyapatite, which provides resistance to compression.[2] The bone cortical was described as a solid containing a series of voids: haversian canals, Volkmann's canals, and others with an overall porosity of ~10%. Cancellous osseous tissue, on the other hand, is a network of small, interconnected plates of trabeculae with relatively large spaces between them, having a porosity between 50% and 90%.[1],[2],[3] These components are integrated into a rigid structure and microscopically presented a few metabolically active cells and variable vascularization.[4],[5]

The osseous tissue quality encompasses factors other than bone density such as skeletal size, the architecture and three-dimensional orientation of the trabeculae, and matrix properties. Bone quality is not only a matter of mineral content but also of structure. Therefore, it is important to know the bone quantity and quality of the jaws when planning implant treatment.[6],[7] The osseous tissue quality is broken down into four groups: from minimal to severe (1–4), based on bone resorption, that is shown in [Figure 1].
Figure 1: The bone quality of jawbone is broken down into four groups (from minimal to severe, 1–4), based on bone resorption following tooth extraction

Click here to view


Nowadays, dental implant therapy represents the better treatment for an edentulous patient which allows restoration of the masticatory function and esthetics with satisfactory and often spectacular outcomes.[8] To obtain success in these treatments is necessary a high level of bone mass followed by osteointegration with the implant.[9]

To maintain a good bone level is the major obstacle for oral rehabilitation. The treatment of bone loss is difficult, and among many techniques aimed to improve its repair, a wide range of biomaterials has been proposed, and more recently, the photo bioengineering is gaining prominence. This is because its ability to augment the alveolar ridge has gradually expanded the scope of implant dentistry.[5],[10]

Therapies with low-level laser therapy (LLLT) has been used as an adjuvant in dental practice, including dental implants, in view of its potential to accelerate the repair of peri-implant bone tissue beyond biomodulator inflammatory processes. The acceleration of bone regeneration by LLLT may hold potential benefits in clinical therapy in orthopedics and dentistry.[9],[11],[12] However, it is necessary that the laser therapy parameters are clarified in order to obtain the best results from this therapy.[13] In vivo studies have suggested that LLLT can promote new bone formation by inducing proliferation and differentiation of osteoblasts and stimulate angiogenesis, a key component of bone regeneration.[14]

The LLLT may induce a cellular seeking kinesthetic homeostasis, due to the fact that it promotes biostimulation on the molecular and biochemical processes, which typically occur in tissue, besides having analgesic and anti-inflammatory action. The use of laser therapy requires some technical knowledge. It's very important to select the energy applied and its effects in the body and tissues, as well as the form of application.[15]

The actions mechanisms of LLLT included the increase of β-endorphins, the threshold of pain, production of adenosine triphosphate (ATP), microcirculation, and lymphatic flow providing the reduction of the edema.[16],[17],[18] Several therapies have been explored for their ability to enhance bone regeneration such as LLLT, ozone therapy, platelet therapy, and low-intensity pulsed ultrasound.[12]

This work is focused on tissue regeneration associated with LLLT for implantology. This new therapy opens up possibilities for low traumatic repair through induction of the organism response, as well as, the stimulation of its own proliferative activity.


   Methods Top


The Medline and Embase databases were electronically searched for original clinical safety studies with dental implants, platelet-rich fibrin (PRF), platelet-rich plasma (PRP), mesenchymal cells, and laser therapy. Publications from the 15 earliest years available on each database through May 2019 were included. Search terms were LLLT, peri-implant tissue implants, platelet derivatives, and mesenchymal cells. The reference list of each retrieved article was hand searched thoroughly to ensure capture of all pertinent references.

Assessment of methodological quality for tissue effects of low-level laser therapy

The methodological quality of the papers was assessed, mainly focused on main points: (1) involved culture cell of fibroblasts, osteoblasts, and epithelial cells; (2) tested one or more biomaterials; (3) had a concurrent control group; and (4) reported outcomes for specified, fixed time periods. Exclusion criteria for this work were studies where title included only clinical cases and studies that included only bacteriological analysis or mechanical therapy. There were excluded titles that were an abstract only and no full text available. After read materials and method sections were excluded studies that only described bacteriological properties, surgical and/or mechanical therapy in periodontal therapy, and when did not evaluate tissue regeneration. Separate searches of the databases were conducted to identify culture cell studies in vitro involving single biomaterials. Three searches of the databases were conducted using the search terms low laser therapy on tissue regeneration and the limits English language. These articles were manually reviewed.

Assessment of methodological quality of clinical trials

Because these search strategies do not consistently capture all clinical trials that report adverse events, separate searches of the databases were conducted to identify all clinical trials involving single therapy with laser or associated techniques. Three searches of the databases were conducted using the search terms low laser therapy on tissue regeneration and the limits English language. These articles were manually reviewed. The methodological quality of the papers was assessed, mainly focused on main points: (1) involved adults with chronic periodontitis but no serious comorbidities; (2) tested one or more biomaterials; (3) had a concurrent control group; and (4) reported outcomes for specified, fixed time periods.

Qualitative data analysis

After a preliminary evaluation of the selected articles, we found considerable heterogeneity in the study design and outcome variables registered. Hence, a quantitative synthesis by means of a meta-analysis was not possible.


   Review Of The Literature Top


The cell based therapy for regenerative medicine takes places with more emphasis on, stem cells, to repair or replace damaged tissue or organs.[19]

Overall, tissue engineering has three basic requirements: scaffold, growth differentiation signals, and stem cells. The biomaterials represent a fundamental aspect of bone regeneration. It is widely recognized that biomaterials can be tailored to regulate the microenvironment for new bone formation. This essentially means that the ability to manipulate the composition, architecture, and properties of different biomaterials allows one to control the rate of regeneration and ideally enhance the process of new bone formation.[20],[21],[22] The biomaterials with tailored physical, chemical, and geometrical cues can mimic the native stem cell niche to tune the microenvironmental conditions for pluripotent stem cells (PSCs) to preserve their self-renewal capacity or to switch their phenotype, a status ultimately needed to gain regenerative functions ex vivo and in vivo.[23],[24]

Photobiomodulation and tissue repair

The photobiomodulation describes the use of laser therapy on biomedical treatment to stimulate a reparative response need to tissue regeneration. In addition to biostimulation, a few of the other names previously used for this therapy have been included such as low-level laser (or light) therapy (LLLT), low-intensity laser therapy, low-power laser therapy, cold laser, soft laser, photobiostimulation, and photobiomodulation. There is clearly a dismal lack of consistency and consensus on terminology. The most frequently used term is LLLT and is the often-cited Medical Subject Headings term contained in the National Library of Medicine's controlled vocabulary thesaurus.[18]

Laser is a technology that controls the way that energized atoms release photons. The word “laser” is an acronym that stands for light amplification by stimulated emission of radiation. Lasers are different from normal light. A laser light has three distinguishing properties. The first is that the light released is monochromatic. The laser contains one specific wavelength of light. The laser is usually characterized by this wavelength, and the wavelength is determined by the amount of energy released when the electron drops down to its ground state. The wavelength and absorption of the laser determine the laser's interaction with the tissue. The laser light is coherent, which means that all the light waves move in phase together in both time and space. A laser has a very tight beam that is strong and concentrated. A flashlight, by comparison, releases light in many directions; the light is weak and diffuse. A laser beam is collimated, meaning that it consists of waves traveling parallel to each other in a single direction with very little divergence. This allows laser light to be focused on very high intensity [Figure 2]. Ordinary light waves spread and lose intensity quickly.[11],[17]
Figure 2: Preparation of platelet-rich fibrin gel (L-PRF) (a) tube with the platelet post centrifugation constituted by acellular plasma, fibrin clot, and red corpuscle base. (b) Platelet separated of red corpuscle base. (c) Platelet cut. (d) Platelet cut added to platelet-rich fibrin-L and biomaterial

Click here to view


The most cited works of LLLT or photobiomodulation related to implantology studied the treatment of peri-implantitis as well as surface treatment of laser implants and photoablation. The current research is addressing to elaborate methods for coating surfaces of existing implants (biomaterials) so as to achieve the desired biological responses.[20]

We focused on the photobiomodulation as a treatment capable to change the process of tissue repair and treat the musculoskeletal pain. The mechanisms that comprise the photobiomodulation based on regenerative tissue occur on molecular and cells level. Laser light penetrates the tissue and is absorbed by certain chromophores, acting on cell metabolism amplification by increasing the ATP synthesis performed by mitochondria.[25],[26],[27]

The biological effects of LLLT therapy have been reported since 1966.[25] The low-power laser acts primarily on cell organelles, more specifically in mitochondria, lysosome, and cellular membrane, resulting in increased ATP and changing ion transportation within the cells [Figure 3]. There are photoreceptors on the cells so these cells are sensitive to certain wavelengths that absorb photons, and trigger a series of chemical reactions. Thus, the therapeutic laser increases the transport of electrons by increasing the ATP synthesis and proton gradient, leading to increased transport of Na+/H + and Ca2+/Na+. ATP acts controlling cyclic adenosine monophosphate (cAMP) levels, which are favorable to the regenerative process.[10],[11],[13],[25]
Figure 3: Photomodulation on implantology mechanism of action on cells and tissues

Click here to view


However, there is a diversity of irradiation protocols for biostimulation of tissue repair, making that its applicability can be generated doubts in clinical practice by the dental surgeon, requiring a better understanding of its parameters in order to obtain a better use of the laser in dentistry. It is still difficult for one to compare studies about the action of LLLT on the osseointegration of biomaterials because the experimental models and duration of treatments protocols are variable.[13],[25]

The LLLT can modulate the activity of osteoblast-like cells and tissues surrounding implant material. Khadra et al.[28] shown the response to LLLT in vitro, cells exposed to GaAlAs diode laser at dosages of 1.5 or 3 J/cm2 had a tendency toward increased cellular attachment, proliferation, differentiation, and production of transforming growth factor (TGF)-β1, indicating that exposure to laser light of 3 J/cm2 significantly increased osteocalcin and TGF-β1 production, suggesting that LLLT stimulates differentiation of osteoblast-like cells happens in a dose-dependent manner.

The in vitro study evaluated the quantification of Alkaline Phosphatase (ALP) after cell growth in osteogenic medium after 72 h, 96 h, 7 days and 14 days. The cell growth was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) a colorimetric test. It was concluded that 24 h, the cell growth was enhanced 3.6 times by light-emitting diode (LED) (5 J/cm2), 6.8 times by red laser (3 J/cm2), and 10.1 times by red laser (5 J/cm2) in relation to the control group (P < 0.05). At the other periods, there was no influence of irradiation on cell growth (P < 0.05). The production of ALP was not influenced by irradiation at any period of time (P < 0.05). Low-intensity laser and LED have similar effects on the stimulation of cell growth but no effect on cell differentiation.[29]

Khadra et al.[30] showed that a low-intensity red laser at 3 and 5 J/cm2 and LED at 5 J/cm2 had similar effects on stimulating preosteoblast cell growth at early periods of time, although any treatment influenced the ALP production. The osteogenic differentiation of human periodontal ligament cells was increased by low-intensity pulsed laser at a frequency of 1.5 MHz and intensity of 90 mW/cm2 through BMP-Smad signaling pathway.[31] These properties associate laser irradiation and bone surgery and encourage this use both the orthopedic and dental areas, but little is known about its impact on the expression and/or activity of some proteins, i.e., the family of matrix metalloproteinases (MMPs).[32]

Moreover, LLLT at the energy density of 0.43 J/cm2 for two consecutive days induced an enhancement of cell proliferation, and expression of osteopontin and bone sialoprotein. The LLLT and LED, at 10 and 50 J/cm2, differently modulated the metabolism of those cells, increasing proliferation by a mechanism dependent or not of ERK signaling activation and osteogenic differentiation markers such as type I collagen and osteonectin.[33]

Both red and infrared laser phototherapies promoted an enhancement of osteoblast viability at the onset of stimulation regardless of the energy densities tested. However, while both red and infrared were able to induce ALP and MMP-2 activities, only red irradiation induced greater MMP-2 dependent on the wavelength, energy density, and time after laser stimulation [Figure 1]. Several studies involving LLLT show that they promote the acceleration of the healing processes and cell growth in several cell lines.[32],[34]

The wavelengths range from 660 to 980 nm, and there is a power emission variation between 40-100 mW. The energy doses vary from 2.6 to 12 J/per point of application, and four points of 4 J are capable of biomodulation the peri-implant bone tissue. Laser applications should be performed every 48 h, starting in the immediate postoperative period, and for 2–4 weeks in order to obtain the biomodulation effect of laser therapy in implantology, it is essential to know the properties and characteristics of the laser.[13]

Friggi et al.[13] also studied the dose and time of irradiation. It was analyzed the protocols for irradiation of various dental implant companies for dental laser available in the market, combining these data with the literature review and concluded that the most used lasers in dentistry with therapeutic purposes are in the region of the electromagnetic between red and infrared.

Amid et al.[35] in a critical review discuss the clinical results of the LLLT associated with bone regeneration. They observed higher inflammatory cell recruitment and a better tissue organization at the site of the injury, with the presence of granulation tissue and new bone formation. Improved opening of the mid-palatal suture and accelerated bone regeneration are other clinical effects of low-level lasers in the rapid maxillary expansion process.

The results of Soares et al.[5] agree with Amid et al.[35] and add that the effect of different light sources on bone regeneration depends on not only the total dose of radiation but also on the irradiation time and irradiation mode and most importantly the light source used. This group used an animal model and showed that the use of laser phototherapy (780 nm) causes significant tissue responses during repair resulting in quicker repair and improves the quality of newly formed bone.[5],[36],[37],[38]

Pinheiro et al.[39] for understanding the biochemical changes associated with mineralization and remodeling of bone defects studied Wistar rats filled with hydroxyapatite + beta-tricalcium phosphate irradiated or not with two light sources. This work showed results well aligned with previous reports from their group[36],[37],[40],[41],[42] and indicated that the association of laser/LED light with HA graft improved the repair of bone defects. It is important to consider that the findings of improved repair observed in this study are well aligned with other previously reported effects of the isolated or associated use of different biomaterials [Table 1].
Table 1: Low-level laser therapy study setup of the last 5 years relating cell growth and tissue repair to exposure to irradiation, whether or not the use of biomaterials or platelet derivatives

Click here to view


Peplow et al.[47] and Prados-Frutos et al.[14] studied the use of LLLT on implantology. These authors observed that the photobiomodulation provides multiple benefits regarding tissue regenerative by increasing ATP production, osteoblasts differentiation, and enhanced the angiogenesis, contributing toward improved bone mineral deposition, increased osteocyte viability;[33], The photobiomodulation can modulate the specific molecular pathways involved in osteoclast proliferation and differentiation[48],[49] and might be a useful help to the osseointegration process, although in the the current state of this knowledge, there is a lack of human clinical studies [Table 1].

Photobiomodulation associated with platelet derivatives

Platelet-derived factors have been extensively used for clinical and surgical applications requiring tissue regeneration [Figure 2]. The rationale for the widespread use of platelet derivatives in the healing process is due to the abundance and accessibility of critical growth factors (GFs) and other signaling molecules in platelets.[50] Under normal conditions, GF, and bioactive peptides contribute to a well-orchestrated tissue-healing response to injury, which proceeds sequentially through the inflammatory, reparative, and remodeling phase. Platelet GFs have specific cellular targets and promote cell proliferation, differentiation, and chemotaxis by inducing the migration of the cells with morphometric and mitogenic effects [Figure 2].[17]

Complementary therapies, such as LLLT and PRP and PRF, have been studied and used for the repair of bone defects, whereas biomaterial osseointegration and LLLT are believed to enhance bone ingrowth.[25] Therefore, the combined use of LLLT and platelet concentrate (PC) for the treatment of bone defects was investigated using rat calvaria. LLLT effects on the bone repair were demonstrated in several studies,[36],[37] but its effects in combination with PRP/PC were not thoroughly explored, with only a few studies reporting the use of this combination, but not in relation to the bone metabolism.[45],[46]

The platelet-derived products showed regenerative effects controlled by autocrine and paracrine biomolecules including GFs and cytokines contained in platelet alpha granules. Each GF is involved in a phase of the healing process, such as inflammation, collagen synthesis, tissue granulation, and angiogenesis collectively promoting tissue restitution. It has been prepared as PRP, platelet gel, PRF, and platelet eye drops. These products vary in their structure, GFs, composition, and cytokine concentrations.[36],[45],[46]

Garcia et al.[45] studied the LLLT associated with PRP that was better in the regeneration of muscle tissue than the use of these same therapies isolated. These associations have great importance to improve the quality of tissue repair and to reduce treatment time. Contrarious, Jonasson et al.[46] showed conflicting results with Garcia et al.[45] For Jonasson et al.[46] PC treatment associated with autogenous grafts do not enhance bone repair, either alone or in combination with LLLT, they study radiographic, histological, and histomorphometric analyses. However, LLLT alone may contribute to bone repair in association with autogenous bone grafts.

Photobiomodulation associated with stem cells

To satisfy the therapeutic needs of these degenerative diseases, regenerative medicine offers an exciting promise. Regenerative medicine seeks to utilize the therapeutic capacity of stem cells because most of the tissues in the body have their own endogenous stem cells to regenerate upon injury.[2],[24]

Nowadays, it was verified that stem cells from the oral cavity are master cells that could generate tissues and organs.[24] Dental stem cells display multifactorial potential such as high proliferation rate, multi differentiation ability, easy accessibility, high viability, and easy to be induced to distinct cell lineages. Dental mesenchymal stem cells (DMSCs) are isolated from dentoalveolar tissues and have characteristic stem cell surface markers. They are present in periodontal ligament, alveolar bone, and in the pulp of both deciduous and permanent teeth.[4],[20],[24]

Nevertheless, there is a great search for more accessible sources of stem cell with limited morbidities such as adult stem cells derived from adipose tissue or dental and periodontal tissues. In addition, adult stem cells are not blocked by various religious, ethical, legal, and immune rejection barriers that inevitably arise with the use of ESCs or the high cost associated with the use of induced PSCs (iPSCs) as indicated below.[4],[20],[49]

The LLLT was able to alter the expression of MMP-9 as well as accelerate the production of collagen and increase the total percentage of collagen type III in diabetic animals.[16] LLLT improved the remodeling of the ECM during the healing process in tendons through activation of MMP-2 and stimulation of collagen synthesis. In addition, the pulsed LLLT seems to exert an anti-inflammatory effect over injured tendons, with reduction of the release of proinflammatory cytokines, such as tumor necrosis factor-alpha and the decrease in the inducible nitric oxide synthase activity.[16]

Fekrazad et al.[43] evaluated the effect of LLLT and mesenchymal stem cells (MSCs) on bone regeneration in rabbit calvarial defects. This study showed a significant increase in new bone formation of the LLLT (with a wavelength of 810 nm, power output of 200 mW, power density of 0.2 W/cm2, spot size of 1 cm2, distance of 0.5 cm, period of 20 s, and fluency of 4 J/cm2 per session) group relative to the control and the other two experimental groups. There was no significant difference in the bone formation of the control group compared to the experimental groups filled with MSCs. In addition, inflammation was significantly reduced in the LLLT group compared to the control defects.

The recent studies show that photobiomodulation associated with stem cells is an important strategy used to stimulate and/or increase bone formation. Giannelli et al.[10] investigated the effects of 635 nm diode laser on mouse stem cell proliferation and investigated the underlying cellular and molecular mechanisms, focusing the attention on the effects of laser irradiation on membrane ion channel modulation. It was found that MSC proliferation was significantly enhanced after laser irradiation. Interestingly, the channel inhibition was also able to attenuate the stimulatory effects of diode laser on MSCs, thus providing novel evidence to expand our knowledge on the mechanisms of biostimulation after LLLT. These findings suggest that diode laser may be a valid approach for the preconditioning of MSCs in vitro before cell transplantation.

Although several studies have reported on the isolated effects of LLLT or stem cells on bone regeneration, there are just very few studies assessing the synergistic effect in vivo.


   Discussion Top


The field of tissue engineering and regenerative medicine has been rapidly expanded through the multidisciplinary integration of research and clinical practice in response to the unmet clinical needs for reconstruction of the dental, oral, and craniofacial structures.

The biomaterials used on bone repair techniques shall allow osteoblasts to build bridges between its granules and integrate with other osteoblasts providing support for both proliferation and differentiation at earlier phases of the repair. This will cause an intrinsic stimulation of new bone formation supported by the activation and absorption of MSCs into surfaces allowing fully differentiated osteoblasts to support bone matrix production.[5],[38]

The formation of new bone around titanium implants was related using membrane technique and various bone-grafting materials (including autogenous grafts, freeze-dried bone grafts, hydroxyapatite, and xenografts). Although the results of these investigations indicate that augmentation is clinically successful for various graft materials, it is questionable for these materials. The autogenous bone has adequate osteogenic potential and biomechanical properties, which currently remains the material of choice and is available for the bone reconstructive procedure. However, its use is limited due to donor site morbidity and limited amount of graft materials available.[9]

After direct irradiation with lasers emitting in the red and infrared on the cells, there are primary mechanisms of action justified by the acceleration of the electron transport in respiratory modulation, changes in the redox properties of the components of the respiratory chain, photoexcitation of its electronic states promoting the generation of singlet oxygen, transient localized heating in absorbing chromophores, and increased production of superoxide anions, with the subsequent increase of H2O2 concentration, which is the product of its dismutation. Furthermore, secondary mechanisms of action occur including a cascade of reactions linked to changes in cellular homeostasis parameters (pH, calcium concentration, the concentration of cAMP, and ATP) and a dynamic balance between oxidants and redactors.

LLLT also stimulates the repair process of the radiation-related damages in alveolar bone and can enhance mineralization in sockets. Most of the cited studies agree that low-level laser therapies were effective on alveolar bone healing and that energy for dose media of 10 J/cm2 did not have an inhibition effect on bone regeneration. The energy density of the laser was 0.7–9 J/cm2 for cell proliferation stimulation on in vitro studies. The power used for visible light was 30–110 mW and that used for infrared light was 50–800 mW.[43] The results were dependent on different parameters; therefore, optimization of parameters was used in light therapy.

The biomaterials and matrices have an important role to control stem cell behaviors, specifically iPSCs. There is a prominent difference between PSCs and adult stem cells in their differentiation capacities. The therapeutic potential of mesenchymal stromal cells depends on their ability to survive and proliferate under adverse in vivo scenarios in a particular disease. Perez et al.[24] related the importance of the biomaterial guiding these cells; in most of the sites of injury, especially in diabetic wounds, there can be hypoxia, hyperglycemia, and ischemia, leading to a lack of nutrients.

The dentists and medical scientist must be encouraging and warn over the potential of the use of extracted teeth that can become a source of stem cells and make them aware of the regenerative potential that is often wasted. Moreover, widespread among professionals and patients could be critical for regenerative stem cell therapy since if more people know the forms of treatment and the applications that exist, more studies will be done. Until now, the use of dental stem cells has limited clinical applications in dentistry because of the structural complexity of the teeth.[21] To this end, a growing number of researches about the molecular signaling and GFs are available for specific cells.

Although investigators have attempted to use such cells to regenerate different tissues, currently the regenerative modalities using stem cells are not standard therapies approved by major regulatory bodies, such as Food and Drug Administration. It is a concern in the literature that the introduction of GF biologics and cells has the potential to improve the biomimetic properties and regenerative potential of scaffold-based delivery platforms for next-generation patient-specific treatments with greater clinical outcome predictability.

More studies in relation to photobiomodulation and stem cells are needed. It is known of the importance of these two elements for the implantology. Although the results of the association are not clear, no clinical studies have been done in this respect.


   Conclusions Top


The LLLT is well documented; nevertheless, the multiple parameters of equipment mentioned in the literature can be doubt about the application for tissue regeneration. The better results for bone regeneration associating LLLT with platelet derivative or biomaterial were observed with the application of 4–5 J/cm2 of energy in a wavelength on the range of 660–840 nm. Further research is necessary to identify the optimal technique parameters of the LLLT: frequency/duration of irradiations, distance between the cells and the laser spot/probe to increase the proliferation of cells and for the future DMSCs, and assess its impact on replicative senescence, as well as determine the feasibility of its use on the implantology.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Baldwin JG, Wagner F, Martine LC, Holzapfel BM, Theodoropoulos C, Bas O, et al. Periosteum tissue engineering in an orthotopic in vivo platform. Biomaterials 2017;121:193-204.  Back to cited text no. 1
    
2.
Berthiaume F, Maguire TJ, Yarmush ML. Tissue engineering and regenerative medicine: History, progress, and challenges. Annu Rev Chem Biomol Eng 2011;2:403-30.  Back to cited text no. 2
    
3.
Liu J, Ruan J, Weir MD, Ren K, Schneider A, Wang P, et al. Periodontal bone-ligament-cementum regeneration via scaffolds and stem cells. Cells 2019;8:537.  Back to cited text no. 3
    
4.
Qasim M, Chae DS, Lee NY. Advancements and frontiers in nano-based 3D and 4D scaffolds for bone and cartilage tissue engineering. Int J Nanomed 2019;14:4333-51.  Back to cited text no. 4
    
5.
Soares LG, Marques AM, Guarda MG, Aciole JM, dos Santos JN, Pinheiro AL. Influence of the λ780nm laser light on the repair of surgical bone defects grafted or not with biphasic synthetic micro-granular hydroxylapatite+Beta-Calcium triphosphate. J Photochem Photobiol B 2014;131:6-23.  Back to cited text no. 5
    
6.
Le BQ, Nurcombe V, Cool SM, Van Blitterswijk CA, De Boer J, La Pointe VL. The components of bone and what they can teach us about regeneration. Materials 2018;11:14.  Back to cited text no. 6
    
7.
Ribeiro-Rotta RF, Lindh C, Pereira AC, Rohlin M. Ambiguity in bone tissue characteristics as presented in studies on dental implant planning and placement: A systematic review. Clin Oral Implants Res 2011;22:789-801.  Back to cited text no. 7
    
8.
Neves FD, Mendes FA, Borges TF, Mendonça DB, Prado MM, Zancopé K. Masticatory performance with different types of rehabilitation of the edentulous mandible. Braz J Oral Sci 2015;14:186-9.  Back to cited text no. 8
    
9.
Chellini F, Giannelli M, Tani A, Ballerini L, Vallone L, Nosi D, et al. Mesenchymal stromal cell and osteoblast responses to oxidized titanium surfaces pre-treated withλ=808nm GaAlAs diode laser or chlorhexidine: In vitro study. Lasers Med Sci 2017;32:1309-20.  Back to cited text no. 9
    
10.
Giannelli M, Chellini F, Sassoli C, Francini F, Pini A, Squecco R, et al. Photoactivation of bone marrow mesenchymal stromal cells with diode laser: Effects and mechanisms of action. J Cell Physiol 2013;228:172-81.  Back to cited text no. 10
    
11.
Green J, Weiss A, Stern A. Lasers and radiofrequency devices in dentistry. Dent Clin North Am 2011;55:585-97.  Back to cited text no. 11
    
12.
Acar AH, Yolcu Ü, Altındiş S, Gül M, Alan H, Malkoç S. Bone regeneration by low-level laser therapy and low-intensity pulsed ultrasound therapy in the rabbit calvarium. Arch Oral Biol 2016;61:60-5.  Back to cited text no. 12
    
13.
Friggi TR, Rodrigues RM, Feitosa PC, Romeiro RL. Laserterapia aplicada à implantodontia: Análise comparativa entre diferentes protocolos de irradiação./Laser therapy applied to dental implants: A comparative analysis of different irradiation protocols. Innov Implant J Biomater Esthet 2011;6:44-8.  Back to cited text no. 13
    
14.
Prados-Frutos JC, Rodríguez-Molinero J, Prados-Privado M, Torres JH, Rojo R. Lack of clinical evidence on low-level laser therapy (LLLT) on dental titanium implant: A systematic review. Lasers Med Sci 2016;31:383-92.  Back to cited text no. 14
    
15.
Nagata MJ, Santinoni CS, Pola NM, de Campos N, Messora MR, Bomfim SR. Bone marrow aspirate combined with low-level laser therapy: A new therapeutic approach to enhance bone healing. J Photochem Photobiol B 2013;121:6-14.  Back to cited text no. 15
    
16.
Da Silva AA, Leal-Junior EC, Alves AC., Rambo CS, dos Santos SA, Vieira RP, et al. Wound-healing effects of low-level laser therapy in diabetic rats involve the modulation of MMP-2 and MMP-9 and the redistribution of collagen Types I and III. J Cosmet Laser Ther 2013;15:210-6.  Back to cited text no. 16
    
17.
Asnaashari M, Zadsirjan S. Application of laser in oral surgery. J Lasers Med Sci 2014;5:97-107.  Back to cited text no. 17
    
18.
Anders JJ, Lanzafame RJ, Arany PR. Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg 2015;33:183-4.  Back to cited text no. 18
    
19.
Horst OV, Chavez MG, Jheon AH, Desai T, Klein OD. Stem cell and biomaterials research in dental tissue engineering and regeneration. Dent Clin North Am 2012;56:495-520.  Back to cited text no. 19
    
20.
Györgyey A, Ungvári K, Kecskeméti G, Kopniczk J, Hopp B, Oszkó A, et al. Attachment and proliferation of human osteoblast-like cells (MG-63) on laser-ablated titanium implant material. Mater Sci Eng C Mater Biol Appl 2013;33:4251-9.  Back to cited text no. 20
    
21.
Pilipchuk SP, Plonka AB, Monje A, Taut AD, Lanis A, Kang B, et al. Tissue engineering for bone regeneration and osseointegration in the oral cavity. Dent Mater 2015;31:317-38.  Back to cited text no. 21
    
22.
Thrivikraman G, Athirasala A, Twohig C, Boda SK, Bertassoni LE. Biomaterials for craniofacial bone regeneration. Dent Clin North Am 2017;61:835-56.  Back to cited text no. 22
    
23.
Kim KL, Han DK, Park K, Song SH, Kim JY, Kim JM. Enhanced dermal wound neovascularization by targeted delivery of endothelial progenitor cells using an RGD-g-PLLA scaffold. Biomaterials 2009;30:3742-8.  Back to cited text no. 23
    
24.
Perez R A, Choi SJ, Han CM, Kim JJ, Shim H, Leong KW, Kim HW. Biomaterials control of pluripotent stem cell fate for regenerative therapy. Prog Mater Sci 2016;82:234-93.  Back to cited text no. 24
    
25.
Obradović RR, Kesić LG, Pesevska S. Influence of low-level laser therapy on biomaterial osseointegration: A mini-review. Lasers Med Sci 2009;24:447-51.  Back to cited text no. 25
    
26.
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;40:516-33.  Back to cited text no. 26
    
27.
Guedes CC, Filho SA, Faria PR, Sabino-Silva AR, Cardoso SV. Variation of energy in photobiomodulation for the control of radiotherapy-induced oral mucositis: A clinical study in head and neck cancer patients. Int J Dent 2018;2018:4579279.  Back to cited text no. 27
    
28.
Khadra M, Lyngstadaas SP, Haanaes HR, Mustafa K. Effect of laser therapy on attachment, proliferation and differentiation of human osteoblast-like cells cultured on titanium implant material. Biomaterials 2005;26:3503-9.  Back to cited text no. 28
    
29.
Pagin MT, De Oliveira FA, Oliveira RC, Sant'Ana AC, De Rezende ML, Greghi SL, et al. Laser and light-emitting diode effects on preosteoblast growth and differentiation. Lasers Med Sci 2014;29:55-9.  Back to cited text no. 29
    
30.
Khadra M, Kasem N, Lyngstadaas SP, Haanaes HR, Mustafa K. Laser therapy accelerates initial attachment and subsequent behaviour of human oral fibroblasts cultured on titanium implant material. A scanning electron microscope and histomorphometric analysis. Clin Oral Implants Res 2005;16:168-75.  Back to cited text no. 30
    
31.
Yang Z, Ren L, Deng F, Wang Z, Song J. Low-intensity pulsed ultrasound induces osteogenic differentiation of human periodontal ligament cells through activation of bone morphogenetic protein-smad signaling. J Ultrasound Med 2014;33:865-73.  Back to cited text no. 31
    
32.
Oliveira FA, Matos AA, Matsuda SS, Buzalaf MA, Bagnato VS, Machado MA, et al. Low level laser therapy modulates viability, alkaline phosphatase and matrix metalloproteinase-2 activities of osteoblasts. J Photochem Photobiol B 2017;169:35-40.  Back to cited text no. 32
    
33.
Oliveira FA, Matos AA, Santesso MR, Tokuhara CK, Leite AL, Bagnato VS, et al. Low intensity lasers differently induce primary human osteoblast proliferation and differentiation. J Photochem Photobiol B 2016;163:14-21.  Back to cited text no. 33
    
34.
Volpato LE, Oliveira RC, Espinosa MM, Bagnato VS, Machado MA. Viability of fibroblasts cultured under nutritional stress irradiated with red laser, infrared laser, and red light-emitting diode. J Biomed Opt 2011;16:075004.  Back to cited text no. 34
    
35.
Amid R, Kadkhodazadeh M, Ahsaie MG, Hakakzadeh A. Effect of low-level laser therapy on proliferation and differentiation of the cells contributing in bone regeneration. J Lasers Med Sci 2014;5:163-70.  Back to cited text no. 35
    
36.
Pinheiro AL, Soares LG, Barbosa AF, Ramalho LM, Santos JN. Does LED phototherapy influence the repair of bone defects grafted with MTA, bone morphogenetic proteins, and guided bone regeneration? A description of the repair process on rodents. Lasers Med Sci 2012;27:1013-24.  Back to cited text no. 36
    
37.
Pinheiro AL, Soares LG, Cangussú MC, Santos NR, Barbosa AF, Silveira L Jr. Effects of LED phototherapy on bone defects grafted with MTA, bone morphogenetic proteins and guided bone regeneration: A Raman spectroscopic study. Lasers Med Sci 2012;27:903-16.  Back to cited text no. 37
    
38.
Tim CR, Pinto KN, Rossi BR, Fernandes K, Matsumoto MA, Parizotto NA, et al. Low-level laser therapy enhances the expression of osteogenic factors during bone repair in rats. Lasers Med Sci 2014;29:147-56.  Back to cited text no. 38
    
39.
Pinheiro AL, Soares LG, Marques AM, Aciole JM, de Souza RA, Silveira L Jr. Raman ratios on the repair of grafted surgical bone defects irradiated or not with laser (λ780 nm) or LED (λ850 nm). J Photochem Photobiol B 2014;138:146-54.  Back to cited text no. 39
    
40.
Pinheiro AL, Gerbi ME, Limeira FA Jr., Ponzi EA, Marques AM, Carvalho CM, et al. Bone repair following bone grafting hydroxyapatite guided bone regeneration and infrared laser photobiomodulation: A histological study in a rodent model. Lasers Med Sci 2009;24:234-40.  Back to cited text no. 40
    
41.
Lopes CB, Pacheco MT, Silveira L, Cangussu MC, Pinheiro 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. J Biomed Mater Res A 2010;4:1257-63.  Back to cited text no. 41
    
42.
Pinheiro AL, Santos NR, Oliveira PC, Aciole GT, Ramos TA, Gonzalez TA, et al. The efficacy of the use of IR laser phototherapy associated to biphasic ceramic graft and guided bone regeneration on surgical fractures treated with miniplates: A Raman spectral study on rabbits. Lasers Med Sci 2013;28:513-8.  Back to cited text no. 42
    
43.
Fekrazad R, Sadeghi-Ghuchani M, Eslaminejad MB, Taghiyar L, Kalhori KA, et al. The effects of combined low-level laser therapy and mesenchymal stem cells on bone regeneration in rabbit calvarial defects. J Photochem Photobiol B 2015 151:180-5.  Back to cited text no. 43
    
44.
Bouvet-Gerbettaz S, Merigo E, Rocca JP, Carle GF, Rochet N. Effects of lowlevel laser therapy on proliferation and differentiation of murine bone marrow cells into osteoblasts and osteoclasts. Lasers Surg Med 2009;41:291-7.  Back to cited text no. 44
    
45.
Garcia TA, Camargo RC, Koike TE, Ozaki GA, Castoldi RC, Filho JC. Histological analysis of the association of low-level laser therapy and platelet-rich plasma in regeneration of muscle injury in rats. Braz J Phys Ther 2017;21:425-33.  Back to cited text no. 45
    
46.
Jonasson TH, Zancan R, de Oliveira LA, Fonseca AC, Silva MC, Giovanini AF, et al. Effects of low-level laser therapy and platelet concentrate on bone repair: Histological, histomorphometric, immunohistochemical, and radiographic study. J Craniomaxillofac Surg 2017;45:1846-53.  Back to cited text no. 46
    
47.
Peplow PV, Chung TY, Ryan B, Baxter GD. Laser photobiomodulation of gene expression and release of growth factors and cytokines from cells in culture: A review of human and animal studies. Photomed Laser Surg 2011;29:285-304.  Back to cited text no. 47
    
48.
Campanha BP, Gallina C, Geremia T, Loro RC, Valiati R, Hubler R, et al. Low-level laser therapy for implants without initial stability. Photomed Laser Surg 2010;28:365-9.  Back to cited text no. 48
    
49.
Maluf AP, Maluf RP, Brito CR, Franca FM, De Brito RB Jr. Mechanical evaluation of the influence of low-level laser therapy in secondary stability of implants in mice shinbones. Lasers Med Sci 2010;25:693-8.  Back to cited text no. 49
    
50.
Martínez CE, Smith PC, Alvarado VA. The influence of platelet-derived products on angiogenesis and tissue repair: A concise update. Front Physiol 2015;6:290.  Back to cited text no. 50
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
   Methods
    Review Of The Li...
   Discussion
   Conclusions
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed7472    
    Printed14    
    Emailed0    
    PDF Downloaded131    
    Comments [Add]    

Recommend this journal