¹Elaine Aparecida Rocha Domingues

²Fabiane Urizzi

³Fernanda Roberta de Souza

¹Doutora em Ciências da Saúde pela Universidade Estadual de Campinas (Unicamp), Campinas, Brasil.

ORCID: https://orcid.org/0000-0002-7589-2344

²Doutora em Ciências da Saúde pela

Universidade Estadual de Londrina. Paraná, Brasil.

ORCID: https://orcid.org/0000-0003-4263-1890

³Enfermeira. São Paulo, Brasil.

ORCID: https://orcid.org/0000-0001-5577-3834

Autor correspondente

Elaine Aparecida Rocha Domingues

Rua Travessa Costa de Lavis, 59, Campo Grande, Mato Grosso do Sul, Brasil.

CEP: 79113114.

Email: elainerocha.contato@gmail.com Telefone: +55(35)988800905

ABSTRACT

Objective: To synthesize the evidence available in the scientific literature on the use of photodynamic therapy in tissue repair of acute or chronic wounds among adult patients. Method: This is a scoping review, which included investigations with samples that consisted of patients over the age of 18 years, undergoing photodynamic therapy in acute or chronic wounds. Scientific articles that addressed children, animals and in vitro, and therapy in tumor, corneal and oral lesions were excluded. For the selection of articles, the LiLACS, MEDLINE, and IBEC databases were consulted, without limitation of the initial period until April 2021. Results: Of the 15 articles included, (66.6%) referred to the assessment of the reduction in the bacterial load of the chronic or infected wounds. Among the scientific reports that addressed the use of therapy in chronic infected wounds, there was a significant reduction in the bacterial load of microorganisms. Conclusion: The studies have a low level of methodological evidence. However, it was possible to observe that photodynamic therapy does not cause resistance to microorganisms and has specific action on devitalized tissues, without damaging healthy cells.

Keywords: Healing; Injuries; Photochemotherapy; Wound Infection; Low-Level Light Therapy.

RESUMEN

Objetivo: Sintetizar la evidencia disponible en la literatura científica sobre el uso de la terapia fotodinámica en la reparación tisular de heridas agudas o crónicas en pacientes adultos.Método: se trata de una revisión del alcance, que incluyó investigaciones cuya muestra estuvo constituida por pacientes mayores de 18 años. ancianos, sometidos a terapia fotodinámica en heridas agudas o crónicas. Se excluyeron los artículos científicos que abordaran niños, animales e in vitro, terapia en lesiones tumorales, corneales y orales. Para la selección de artículos se consultaron las bases de datos LiLACS, MEDLINE e IBEC, sin limitación del período inicial hasta abril de 2021. Resultados: De los 15 artículos incluidos, (66,6%) se refirió a la valoración de la reducción de la carga bacteriana de las lesiones crónicas o infectadas. Entre los informes científicos que abordaron el uso de terapia en lesiones crónicas infectadas, hubo una reducción significativa en la carga bacteriana de microorganismos. Conclusión: Los estudios tienen un bajo nivel de evidencia metodológica. Sin embargo, se pudo observar que la terapia fotodinámica es un método que no causa resistencia a los microorganismos y tiene acción específica sobre los tejidos desvitalizados, sin dañar las células sanas.y tiene acción específica sobre tejidos desvitalizados, sin dañar las células sanas.

Palabras clave: Curación; Lesiones; Fotoquimioterapia; Infección de Heridas; Terapia por Luz de Baja Intensidad.

RESUMO

Objetivo: Sintetizar as evidências disponíveis na literatura científica sobre a utilização da terapia fotodinâmica no reparo tecidual de feridas agudas ou crônicas entre pacientes adultos Método: trata-se de uma revisão de escopo, que incluiu investigações cuja amostra foi composta por pacientes com idade superior a 18 anos, submetidos a terapia fotodinâmica em feridas agudas ou crônicas. Excluíram-se artigos científicos que abordaram crianças, animais e in vitro, terapia em lesões tumorais, córnea e bucal. Para a seleção dos artigos foram consultadas as bases LILACS, MEDLINE e IBECS, sem limitação do período inicial até abril de 2021. Resultados: Dos 15 artigos incluídos, (66,6%) referiu-se à avaliação da redução da carga bacteriana das lesões crônicas ou infectadas. Dentre os relatos científicos que abordaram o uso da terapia em lesões crônicas infectadas, foi verificada redução significativa da carga bacteriana de microrganismos. Conclusão: Os estudos são de baixo nível de evidência metodológica. Entretanto, foi possível observar que a terapia fotodinâmica é um método que não ocasiona resistência aos microrganismos e possui ação específica nos tecidos desvitalizados, sem danificar as células saudáveis.

Palavras-chave: Cicatrização; Lesões; Fotoquimioterapia; Infecção dos Ferimentos; Terapia com Luz de Baixa Intensidade.

INTRODUCTION

The skin is the largest organ in the human body, providing the individual with mechanical, chemical, microbiological, and physiological protection, in addition to being responsible for the synthesis of vitamin D, for providing sensations, and forregulation of fluids, electrolytes, and thermal balance¹.

As it is the exposed organ of the human body, the skin is susceptible to intrinsic factors such as nutritional deficit, impaired perfusion, reduced mobility, body weight, and advanced age. Among the extrinsic factors, humidity and pressure are highlighted, which progressively alter its structural integrity and physiological function, increasing the possibility of damage².

When a skin injury occurs, the healing process begins with a sequence of interdependent events, aimed at restoring its function. These steps are didactically divided into: inflammatory, proliferation, and remodeling³.

The inflammatory phase involves the chemotaxis of leukocytes with the functionality of phagocytosing foreign bodies and microorganisms to prepare the wound bed. The proliferation phase is characterized by angiogenesis and formation of extracellular matrix. Later the wound contracts and there is the development of repair tissue, called epithelialization^3-4.

When the tissue repair process is slow, that is, the wound stagnates in the inflammatory phase, and does not progress in the orderly stages of epithelial recovery, it is classified as a chronic wound. These wounds are usually associated with chronic diseases and with reoccurrence⁴. On the other hand, acute wounds present recovery that follows the healing processes and in the time allocated for regeneration, such as surgical injuries³.

Chronic wounds are a clinical problem that negatively impacts the life of the individual, initially due to the cause, fear of care, and consequent failure in self-care, which, when not performed properly, prolongs the time needed for wound healing and the cost of treatment⁵.

The treatment of acute and chronic wounds is associated with high expenditures, amounting to from R$ 28.1 billion to R$ 96.8 billion⁶, and these data tend to increase annually, due to the significant prevalence of chronic diseases that can affect healing⁷. In addition, at least 50% of antibiotic-resistant infections appear in wounds, whether acute or chronic, accounting for more than 11,000 annual deaths resulting from methicillin-resistant Staphylococcus aureus (MRSA) infections⁸.

In addition to the mortality caused by infected wounds, antibiotic resistance adds considerable costs, further straining the healthcare system. Approximately 8 million reais refer to additional hospital days, 20 billion to excess health-related costs, and 35 billion to indirect expenses related to the social factor each year⁸. This high expenditure also affects the individual and family members, as they are removed from their work activities, impairing their income and interrupting their daily activities⁶.

Treatment depends on different factors, from the presence of infection, type of wound, tissue present, exudate, pain, associated morbidities, and nutritional and hemodynamic status. These conditions directly influence the therapy used; whether conventional dressings and in some cases, debridement, grafts are necessary, or advanced therapies such as negative pressure, ozone therapy, hyperbaric chamber, and laser therapy^9-10.

Among the technologies used, photodynamic therapy (PDT) deserves to be highlighted, as it demonstrates the ability to change cellular behavior, and is used as an adjuvant treatment since it has analgesic, anti-inflammatory, and accelerated wound healing properties^11-12.

PDT is the interrelationship of three components, photosensitizer, light, and oxygen. This chemical reaction depends on the wavelength of the light¹¹. The wavelength of the device ranges from 570 nm to 690 nm. Methylene blue or toluidine is used as a photosensitizer, applied to the wound bed, and left for five minutes for dye absorption before beginning the application. Application frequency varies from once a week to once a month¹³.

The mechanism of action begins when the energy of the low-level laser is transferred to the photosensitizer, at which time a cellular reaction occurs, producing free radicals that interact with oxygen to form reactive oxygen species, which have a cytotoxic action to microorganisms¹³.

The use of a low-level laser was evaluated in one of the first reviews, which took place in the 1980s, covering a period of 20 years of studies. Its effects on 15 biological systems were evaluated and showed that low-energy laser radiation has a stimulating effect and high-energy inhibition, recommending the use of the laser to stimulate difficult-to-heal wounds¹⁴. Other studies have pointed out both positive and negative effects on the tissue repair process in acute and chronic wounds^15-16.

Therefore, the aim of the study was to synthesize the evidence available in the scientific literature on the use of photodynamic therapy in tissue repair of acute or chronic wounds among adult patients.

METHOD

This is a Scoping Review, which refers to a review methodology with the aim of mapping the main concepts, examining how research in a given area is carried out, and listing the main knowledge gaps on a given topic. To prepare the scoping review, we followed the steps suggested by the Joana Briggs Institute (JBI)¹⁷.

To prepare the research question of the review, the PICO17 strategy was used, described below (Table 1).

Table 4 - Distribution of publications in ascending chronological order, author and title, design, sample, objective, main results and limitations.

Study (Author and year)	Design	Sample	Objective	Main results
Ghaffarifar, F; Jorjani, O; Mirshams, M; Miranbaygi, M H; Hosseini, Z K. East Mediterr Health J. 2006²¹.	Case series.	Five Leishmaniasis major lesions	To describe the evolution of Leishmaniasis major lesions after application of photodynamic therapy.	Photodynamic therapy led to the eradication of amastigote forms in the lesions. Effects of: tissue remodeling, lesion reduction, and re-epithelialization were also observed; reduction in inflammatory tissue and hyperpigmentation.
Clayton, T H; Harrison, P V. 2007²²	Case report.	One patient	To describe the use of photodynamic therapy in the antimicrobial action of chronic venous ulcers	Significant evolution was observed in the evolution of the lesion and the culture was negative.
Brown, Stan.J Natl.2012²³.	Randomized clinical trial. 2 stage.	First stage: 32 patients with chronic wounds in the lower limbs and diabetic foot. Second stage: 48 patients with chronic ulcer in the lower limbs.	To describe the antimicrobial action associated with photodynamic therapy on contaminated wounds in reducing bacterial load.	Photodynamic therapy associated with the antimicrobial PPA904 significantly reduced the bacterial load of microorganisms such as methicillin-resistant S. aureus (MRSA). It is a safe therapy for the treatment of chronic ulcers and also reduces the bacterial load after therapy, in addition to accelerating the healing process and preventing infections.
Morley S, Griffiths J, Philips G, Moseley H, Grady CO, Mellish K et al.2013²⁴	Randomized clinical trial.	32 patients with chronic ulcers (16 venous ulcers and 16 diabetic foot).	To evaluate photodynamic therapy in reducing bacterial load and tissue repair of chronic ulcers and diabetic foot.	After 3 months, 50% of patients with actively treated chronic leg ulcers showed complete healing, compared with 12% of patients in the placebo group.
Cappugi P, Comacchi C, Torchia D. 2014²⁵	Case series.	19 patients with venous ulcer.	To evaluate the use of photodynamic therapy in patients with venous ulcers.	All ulcers had Staphylococcus aureus and/or Enterococcus faecalis infection. 15 cases (78.9%) healed after an average of 6.8 sessions.
Lei X, Liu B, Huang Z, Wu J..2015²⁶.	Randomized clinical trial.	Twenty-six patients with chronic ulcer in the lower limbs infected with Pseudomonas aeruginosa (PA).	To describe the evolution of antimicrobial activity and healing obtained with the use of topical photodynamic therapy in patients with chronic ulcer in the lower limbs infected with Pseudomona aeruginosa.	Regarding the levels of bacterial contamination by PA on the ulcer surface, there was a significant reduction (p < 0.01)
Reinhard A, Sandborn WJ, Melhem H, Chamaillard M, Biroulet-Peyrin L. 2015²⁷	Expert review	445 patients.	Describe research related to anti-inflammatory, antibacterial, and repair mechanisms using photodynamic therapy.	The results show the role of photodynamic therapy in different lesions (inflammatory bowel disease, arthritis, allergic encephalomyelitis, psoriasis, chronic wounds, and acne vulgaris). It has immunomodulatory and antimicrobial action and accelerates tissue repair.
Rosa LP, da Silva FC, Vieira RL, Tanajura BR, Gusmão AG da S, de OLiveira JM et al. 2017²⁸.	Case report	One patient.	To describe a case report of a pressure injury (PI) in a diabetic patient treated with a combination of photodynamic therapy and cellulose membrane application.	Immediately after one week, the absence of microorganisms was evidenced, aiding the healing process.
Aspiroz, C; Sevil, M; Toyas, C; Gilaberte, Y.2017²⁹	Case series.	Two case studies.	To describe two case studies in chronic lower limb ulcers with infection using photodynamic therapy.	Wound healed in 6 months, with noticeable improvement in the first 3 weeks. After discharge, 2 weekly sessions were performed at home with methylene blue and exposure to daylight for 30 min daily.
Carrinho PM, Andreani DIK, Morete V de A, Iseri S, Navarro RC, Villaverde, AB.2018³⁰.	Experimental, convenience sample, controlled, 2 groups: A and B	12 diabetic patients with ulcers in the lower limbs	To evaluate the morphometric and macroscopic area of lower limb ulcers in diabetic patients undergoing photodynamic therapy comparing two methods of measuring lesions.	Regarding the use of photodynamic therapy, the size of the lesion area reduced when comparing before and after images. Conventional treatment also reduced the area of the lesion (p<0.05) showing the effectiveness of the treatment, but its effect was smaller when compared to the association with photodynamic therapy. In the measurements of the first and last week of both groups, the program showed a significant reduction in the lesion area of the photodynamic therapy group when compared to the conventional treatment group (p < 0.05).
Nesi-Reis V, Nonose-Lera DSSL, Oyama J, Silva-Lalucci MPP, Demarchi IG, Aristides SMA et al.2018³¹	Systematic review.	489 patients.	Summarize effects of photodynamic therapy on cutaneous wound healing in humans.	The main types of wounds treated with the therapy were: chronic ulcers (vasculogenic, mixed, and diabetic), non-melanoma skin cancer, surgical wound, cutaneous leishmaniasis, cheilitis, and actinic keratosis. Regarding the action of therapy, research did not discriminate the specific mechanism in wound healing, however there was a beneficial effect on tissue repair, possibly associated with a reduction in the load of microorganisms present.
Carbinatto FM, de Aquino AE, Coelho VHM, Bagnato VS. 2018³²	Case report.	One patient with two lesions: arterial and venous ulcer.	To describe a case report of a patient with arterial and venous ulcer treated for 90 days with a combination of photodynamic therapy, low-level laser associated with the application of cellulose membrane.	The results showed a reduction in the ulcer area of 85%, in addition to an important improvement in the pain symptom after 90 days of treatment. The ulcers had existed for 30 and 10 years, and the patient reported several previous treatments and hyperbaric therapy.
Karinja SJ, Spector JA.T.2018⁸	Non-systematic review.	219 patients.	To describe current promising antimicrobial agents for the treatment of infected wounds.	Photodynamic therapy demonstrates action in reducing bacterial load (E. coli, P. aeruginosa, and Acinetobacter baumannii).
Cunha PR, Tsoukas MM, Kroumpouzos G. 2019³³.	Case series	05 patients with erosive pustular dermatosis of the scalp (EPDS)	To describe a review of a protocol using lesion scraping immediately before photodynamic therapy (PDT) associated with aminolevulinic acid and application of silicone gel immediately after photodynamic therapy and twice daily for 4 weeks after the procedure.	All patients responded well to treatment, with only one recurrence occurring 9 months after therapy, with a smaller lesion than the initial one. There were also fewer returns, which increases patient satisfaction and reduces costs. This protocol is efficient, brings satisfactory results in fewer visits with the same effectiveness and the use of silicone gel helps in the healing of the lesion and in reducing the trauma and inflammation induced by the procedure, in addition to bringing comfort and reducing the risk of recurrence.
Krupka M, Bozek A, Aebisher-Bartusik D, Grzegorz C, Krupka-Kawczyk, A. 2021³⁴.	Pilot, randomized study.	Twenty patients with venous ulcers in the lower limbs.	To describe the effectiveness of photodynamic therapy in the treatment of venous ulcers of the lower limbs.	At the 8-month follow-up, 40% of patients in the group presented complete ulcer remission, 30% presented a reduction of more than 50% in ulcer diameter, and 10% presented no response to treatment. The authors concluded that photodynamic therapy is a good alternative in the treatment of venous ulcers since it is a minimally invasive alternative, with many benefits and without serious side effects.

According to the search results, the years of publication ranged from 2006 to 2021, with 2018 presenting the most articles (4;26.7%), followed by 2007 (3;20%), and 2015 and 2017 with two studies each year (13.3%). Regarding the places of publication, five articles (33.3%) were from Brazil, three (20%) were British and Iran, Italy, France, Spain, Poland, China, and the United States presented one (6.7%) referenced article each.

The studies were carried out by physicians (12;80%), followed by biomedical scientists (2;13.3%), and one biochemist (1;6.7%). All articles were published in English. Regarding the study methodologies, seven (46.6%) were case studies, four (26.6%) were randomized clinical trials, two (13.3%) were non-systematic literature reviews, one (6.7%) was a systematic literature review, and one (6.7%) article had an experimental methodology.

In the studies that cited the ages of the participants, they ranged from 48 to 90 years in women and 21 to 82 years in men.

Regarding the types of lesions submitted to PDT, there was a greater number of citations in infected and/or chronic lesions (vascular and diabetic foot) with 46.6%, followed by psoriasis (15%), acne (10%), surgical wounds (6.6%), leishmaniasis (5%), and actinic keratosis (3.3%). Alongside PDT, among the photosensitizers (PS) used topically, in decreasing order of frequency, are delta-aminolevolinic acid (ALA), PPA904 (pyropheophorbide-a or 3,7-bis-phenothiazin), curcumin, methylene blue, and methyl aminolevulinate (MAL). The only photosensitizer used intravenously was meso-tetra-hydroxyphenyl-chlorin (mTHPC).

Another variable to be considered is the wavelength variation and maximum dose of joules applied together with the FSs, being: ALA (417-750nm- 200J), PPA 904 (570-680nm- 50J), curcumin (450-660nm-10J), methylene blue (660nm-129J), MAL (630-635nm-37J), and mTHPC (652nm-10J).

Field studies, in which topical therapy was necessary to follow up the evaluation in comparison with PDT, cited hydrofiber with silver, silver sulfadiazine, curcumin, ointment with collagenase and chloramphenicol, and octenilin gel. Another aspect highlighted was the variation in time between the application of the photosensitizing agent and PDT: in the studies on the use of ALA, this ranged from one and a half to four hours, for curcumin all studies cited 30 minutes, methylene blue from 05 at 30 minutes, and PPA-904 was 15 minutes. Regarding the number of weekly sessions and duration of therapy, different frequencies and periods were observed.

Of the 15 articles selected for the research, (53.3%) were related to the assessment of the reduction in the bacterial load of the lesions, evidenced in the swab collections performed before and after photodynamic therapy^23,26.

The microorganisms studied include Pseudomonas aeruginosa and methicillin-resistant S. aureus (MRSA). A significant reduction in the lesion area was also observed in the group that received PDT associated with photosensitizer (p=0.036 and p<0.01) than in the groups with PDT plus topical therapy or irradiated light and octenilin gel^30,34.

DISCUSSION

North American statistics point to a prevalence of wounds of around 14% of the world population. Other studies suggest that the rates may be higher, reaching 22.8%³⁵. In Brazil, statistical records on the prevalence or incidence of wounds in the Brazilian population are scarce, especially for chronic wounds³⁶.

Considering that the present study found a greater number of studies related to chronic and/or infected wounds, it is important to consider that the slow healing process directly affects lifestyle, due to pain and mobility difficulties, leading the individual to social isolation, an inability to work, loss of self-esteem, and depression, with studies pointing to a decrease in the quality of life of these individuals³⁶.

Acute and chronic wounds generate high costs for the individual, family members, and health system. The total or partial loss of the integument, the protective layer, predisposes the entry of microorganisms, which can delay the tissue repair process. When the evaluation and treatment are not effective, it can progress to a critical colonization, and later evolve to a local and even systemic infection, causing a great impact on the lives of affected individuals^37,38.

Excessive use of local and systemic antibiotics contributes to the high prevalence of multidrug-resistant infections. Furthermore, the limited infiltration of drugs in infected areas is aggravated by the morbidities associated with the individual and reduces the effectiveness of conventional therapies, causing a delay in the healing process²⁸.

In this context, the use of photodynamic therapy (PDT) deserves to be highlighted, because from the results presented, it is evident that the therapy favors the tissue repair process in acute and chronic wounds, with an effect primarily on infection, highlighting its important role as adjuvant treatment^8,28.

Most of the publications had the main objective of evaluating the effect of the therapy on the reduction and control of microorganisms. Research emphasizes that photodynamic therapy is an alternative method to treat infections and deserves to be highlighted in a scenario where there are high rates of antimicrobial resistance and low options for these drugs, which makes it difficult to treat infected wounds⁸.

A study analyzed the evolution of healing and antimicrobial reduction in lower limb ulcers infected with Pseudomonas aeruginosa. The results were promising, highlighting the improvement in the healing process and attenuation of the bacterial flora²⁶.

Although practical experience in the use of PDT in the treatment of ulcers is limited, some studies point to the resolution of two cases analyzed with the presence of species of fusarium, pseudomonas, and other difficult-to-treat bacteria, but with the use of PDT, patients achieved healing and epithelialization of ulcers without the need for high-cost therapies, showing another advantage of this therapy ²⁹.

PDT is a method that does not cause resistance to microorganisms and has a specific action on pathological tissues, without damaging healthy cells. The therapy is well tolerated by patients and does not cause painful sensitivity. It is a non-invasive, low-cost, fast, safe tool with minimal adverse events³⁹.

Another aspect to be considered is that although studies presented low evidence and a non-significant sample, it is important to consider the use of PDT in the treatment of infected lesions, since its principle mode of action is the use of photosensitizing substances in biological tissues that, after activation by light are capable of triggering chemical reactions, providing a photochemical effect that leads to cell death⁴⁰.

The classic study published in 1985¹³ recommends the use of the laser with doses that aim to stimulate healing as well as doses that cause inhibition and eradication of devitalized tissues. This application was observed in the included studies, where PDT played a role in the reduction in the area and progress of the clinical aspects of the wounds, such as attenuation of exudate, devitalized tissue, odor, and intensity of the pain symptom in chronic wounds that remained for years without progress in healing, previously treated with traditional coverages^32,41

Another aspect observed was the lack of standardization of laser application protocols, as well as the lack of complete data necessary for clinical practice, which include: laser parameters and dose, application technique, and type of treatment.¹²Many authors, after reviewing the literature, concluded on the need for standard protocols and more controlled studies so that the use of the laser can become widespread and accepted in the scientific community^42,43.

It is also necessary to consider that there is currently a wide variety of clinical studies using PDT, however the parameters used, as well as the treatment protocols are poorly specified, which limits the comparisons of results and makes clinical replication impossible⁴⁴.

Although the studies are not carried out by nurses, it is emphasized that this is a field of action that brings autonomy in the treatment of wounds. For this, it is necessary to know the patient in their entirety, providing comprehensive care, paying attention to aspects involving the quality of life and seeking alternative treatments to speed up the healing process as well as to prevent complications³⁶.

In the present research, despite having studies with a low level of evidence, it was possible to evaluate PDT related to positive rather than negative aspects when used in chronic and/or infected lesions, since studies with significant statistical analysis indicated this conclusion. The lack of a clinical protocol for comparisons was also another limiting aspect.

There is a lack of knowledge about the evolution of acute and/or surgical injuries with the use of PDT. For practical applications, there is a clear need for a protocol that includes data such as: laser and dose parameters, application technique, and type of treatment, in order to distinguish the type of effect to be obtained with the use of PDT, since low doses will provide stimulation and high doses inhibition, both being indications for the promotion of wound healing

CONCLUSION

It was found that PDT is widely used, mainly in the treatment of chronic wounds and in terms of reducing the microbial count. It is noteworthy that PDT is a method that does not cause resistance to microorganisms and has a specific action on devitalized tissues, without damaging healthy cells. The therapy is tolerated by users and does not cause pain or discomfort.

In the present review, studies considered to have a low level of evidence were included. In addition, it was found that the PDT application protocols were different among the included studies. Furthermore, not all parameters necessary for the application of PDT were described in the included investigations, such as: laser and dose parameters, application technique, and type of treatment.

Therefore, it is suggested that new and broader investigations be carried out in order to test PDT application protocols, as well as investigate the effects of using PDT in the treatment of acute wounds.

1. Brennan-Cook J, Turner, RL. Promoting Skin Care for Older Adults. Home Healthcare Now. 2019;37(1):10-16.

2. Garden CRB, Ivastcheschen T, Cabral LPA, Reche PM, Bordin D. Prevalência e fatores associados às lesões elementares em idosos internados. Rev Rene (Online). 2019;20(1):e40384.

3. Squizatto RH, Braz RM, Lopes A de O, Rafaldini BP, Almeida DB de, Poletti, NAA. Perfil dos usuários atendidos em ambulatório de cuidado com feridas. Cogitare Enfermagem. 2017;22(1).

4. Zhao R, Liang H, Clarke E, Jackson C, Xue M. Inflammation in chronic wounds. Int. J. Mol. Sci. 2016;14(12):2085.

5. de Oliveira BGB, Castro JB de A, Grajeiro JM. Panorama epidemiológico e clínico de pacientes com feridas crônicas tratados em ambulatório. Revista enfermagem UERJ. 2013;21(5):612-17.

6. Sen Chandan K. Human Wounds and Its Burden:An Updated Compendium of Estimates. Advances in wound care. 2019;8(2):38-48.

7. Han G, Ceilley R. Chronic wound healing: a review of current management and treatments. Advances in therapy. 2017;34(3):599-610.

8. Karinja SJ, Spector JA. Treatment of Infected Wounds in the Age of Antimicrobial Resistance: Contemporary Alternative Therapeutic Options. Plastic and reconstructive surgery. 2018;142(4):1082-92.

9. Tejiram S, Kavalukas SL, Shupp JW, Barbul A. Wound healing. In: Agren MS. Wound healing biomaterials- therapies and regeneration (electronic book). Woodhead Publishing: Elsevier; 2016. p. 3-39. Cap. 1.

10. Dreifke MB, Jayasuriya AA, Jayasuriya AC. Current wound healing procedures and potential care. Materials Science and Engineering: C. 2015;48(1):651-62.

11. Ozog DM, Rkein AM, Fabi SG, Gold MH, Goldman MP, Lowe NJ, et al. Photodynamic therapy: a clinical consensus guide. Dermatologic Surgery. 2016;42(7):804-27.

12. Damante CA, Marques MM, de Micheli G. Terapia com laser em baixa intensidade na cicatrização de feridas-revisão de literatura. RFO. 2008;13(3):88-93.

13. Brandão MGS, Ximenes MA, Cruz G, Brito EH, Veras V, Barros L, Araújo T. Terapia fotodinâmica no tratamento de feridas infectadas nos pés de pessoas com diabetes mellitus: síntese de boas evidências. REAID [Internet]. 30 jun. 2020 [citado 24 maio 2021];92(30). Disponível em: https://revistaenfermagematual.com.br/index.php/revista/article/view/649

14. Mester E, Mester AF, Mester A. The biomedical effects of laser application. Laser Surg Med. 1985;4:179-81.

15. Ryden H, Persson L, Preber H, Bergstrom J. Effect of low level energy laser irradiation on gingival inflamation. Swedis Dental Journal. 1994;18(1-2):35-41.

16. Damante CA, Greghi SLA, Santana ACP, Passanezi E, Taga R. Histomorphometric study of the healing of human oral mucosa after gingivoplasty and low level laser therapy. Lasers in surgery and medicine. 2004;35:377-84.

17. Joanna Briggs Institute (JBI). Methodology for JBI Scoping Reviews - Joanna Briggs. Australia: JBI (Internet). 2015. [access 10 jun. 2021]. Disponível em: http://joannabriggs.org/assets/docs/sumari/ Reviewers-Manual_Methodology-for-JBI-Scoping-Reviews_2015_ v2.pdf

18. Santos CMC, Pimenta CAM, Nobre MRC. The PICO strategy for the research question construction and evidence search. Rev. Latino-Am. Enfermagem [Internet]. 2007 [access 10 mar 2021];15(3):508-11. Disponível em: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-11692007000300023&lng=en.

19. Galvão TF, Pansani T de SA. Principais itens para relatar revisões sistemáticas e meta-análises: a recomendação prisma. Epidemiol. Serv. Saúde. 2015;24(2):335-42.

20. Melnyk BM, Fineout-Overholt E. Evidence-Based Practice in Nursing and Healthcare: A Guide to Best Practice. Philadelphia, PA Wolters Kluwer Health/Lippincott Williams & Wilkins (Internet). 2011 (access 20 may 2021). 2ª ed Disponível em: http://www.nursingcenter.com/lnc/JournalArticle?Article_ID=1493949#sthash.uKLy63Ky.dpuf

21. Ghaffarifar F, Jorjani, O, Mirshams M, Miranbaygi, MH, Hosseini ZK. Photodynamic therapy as a new treatment of cutaneous leishmaniasis. East Mediterr Health J. 2006;12(6): 902-8.

22. Clayton TH, Harrison PV. Photodynamic therapy for infected leg ulcers. Br J Dermatol. 2007;156(2): 384-5.

23. Brown S. Clinical antimicrobial photodynamic therapy: phase II studies in chronic wounds. J Natl Compr Canc Netw. 2012;10 Suppl 2: S80-3.

24. Morley S, Griffiths J, Philips G, Moseley H, Grady CO, Mellish K et al. Phase II a randomized, placebo-controlled study of antimicrobial photodynamic therapy in bacterially colonized, chronic leg ulcers and diabetic foot ulcers: a new approach to antimicrobial therapy. Br J Dermatol. 2013;168:617-24.

25. Cappugi P, Comacchi C, Torchia D. Photodynamic therapy for chronic venous ulcers. Acta Dermatovenerol Croat. 2014;22(2):129-31.

26. Lei X, Liu B, Huang Z, Wu J. A clinical study of photodynamic therapy for chronic skin ulcers in lower limbs infected with Pseudomonas aeruginosa. Arch Dermatol Res. 2015:307(1): 49-55.

27. Reinhard A, Sandborn WJ, Melhem H, Chamaillard M, Biroulet-Peyrin L. Photodynamic therapy as a new treatment modality for inflammatory and infectious conditions. 2015;11(5):637-57. Expert Review of Clinical Immunology. DOI: 10.1586/1744666X.2015.1032256.

28. Rosa LP, da Silva FC, Vieira RL, Tanajura BR, Gusmão AG da S, de Oliveira JM et al. Application of photodynamic therapy, laser therapy, and a cellulose membrane for calcaneal pressure ulcer treatment in a diabetic patient: A case report. Photodiagnosis and photodynamic therapy. 2017;19:235-38.

29. Aspiroz C, Sevil M, Toyas C, Gilaberte Y. Photodynamic Therapy With Methylene Blue for Skin Ulcers Infected With Pseudomonas aeruginosa and Fusarium spp. Actas dermosifiliogr. 2017;108(6):e45-e48. doi: 10.1016/j.ad.2016.11.020

30. Carrinho PM, Andreani DIK, Morete V de A, Iseri S, Navarro RC, Villaverde, AB. A Study on the Macroscopic Morphometry of the Lesion Area on Diabetic Ulcers in Humans Treated with Photodynamic Therapy Using Two Methods of Measurement. Photomed Laser Surg. 2018; 36(1):44-50.

31. Nesi-Reis V, Nonose-Lera DSSL, Oyama J, Silva-Lalucci MPP, Demarchi IG, Aristides SMA et al. Contribution of photodynamic therapy in wound healing: A systematic review. Photodiagnosis Photodyn Ther. 2018;21:294-305.

32. Carbinatto FM, de Aquino AE, Coelho VHM, Bagnato VS. Photonic technology for the treatments of venous and arterial ulcers: Case report. Photodiagnosis Photodyn Ther. 2018;22:39-41.

33. Cunha PR, Tsoukas MM, Kroumpouzos G. Erosive Pustular Dermatosis of the Scalp Treated With Aminolevulinic Acid Photodynamic Therapy and Postprocedure Silicone Gel. Dermatol Surg. 2019;45(5):740-743.

34. Krupka M, Bozek A, Aebisher-Bartusik D, Grzegorz C, Krupka-Kawczyk, A. Photodynamic therapy for the treatment of infected leg ulcers- A pilot study. Antibiotics. 2021;10(5): 506. Disponível em: https://doi.org/10.3390/antibiotics10050506

35. Morais GC, Oliveira SH, Soares MJGO. Avaliação de feridas pelos enfermeiros de instituições hospitalares da rede pública. Texto & contexto enferm. [Internet]. 2008 [acesso em: 10 abr 2021]; 17(1):98-105. Disponível em: http://www.scielo.br/scielo.php?pid=S010470 72008000100011&script=sci_arttex

36. Evangelista SG, Magalhães ERM, Moretão DIC, Stival MM, Lima LR. Impacto das feridas crônicas na qualidade de vida de usuários da estratégia de saúde da família. R. Enferm. Cent. O.Min.2012; 2(2):254-63

37. Guest JF, Vowden K, Vowden P. The health economic burden that acute and chronic wounds impose on an average clinical commissioning group/health board in the UK. Journal of Wound Care. 2017; 26(6).

38. Leaper D, Assadian O, Edmiston CE. Approach to chronic wound infections. Br J Dermatol. 2015;173(2):351-8.

39. Silva VB da, Souza SR de, Codá R de P, Fabrício BS, Sória D de AC. Photodynamic therapy in the treatment of injuries in non-melanoma skin cancer: integrative review. RSD [Internet]. 2021Jan.3 [access 5 jun. 2021];10(1):e7410111257. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/11257

40. Prates RA, Yamada AM, Suzuki LC, Eiko HMC, Cai S, Gouw-Soares S., et al. Bactericidal effect of malachite green and red laser on Actinobacillus actinomycetemcomitans. J Protochem Photobiol B. 2007;86(1):70-6.

41. Moura J, Brandão L, Barcessat A. Estudo da Terapia Fotodinâmica (PDT) no reparo de lesões teciduais: estudo de casos clínicos. Estação Científica (UNIFAP). 2018;8(1):103-10. doi: http://dx.doi.org/10.18468/estcien.2018v8n1.p1.

42. Brondon P, stadler I, Lanzafame RJ. A study of the effects of phototherapy does interval on photobiomodulation of cell cultures. Lasers Surg Med. 2005;36:409-13.

43. Walsh LJ, The current status of low-level laser therapy in dentistry. Part 1. Soft tissue applications. Aust Dent J. 1997;42(4):247-54.

44. Baxter D. Laser de baixa intensidade. In: Kitchen S. Eletroterapia: prática baseada em evidência. São Paulo: Manole; 2000. p. 171-89.

Submission: 2022-03-23

Approval: 2022-04-25

P (patient)	Adult patients
I (intervention)	Photodynamic therapy
C (control)	Topical therapies not based on light emission
O (outcome)	Wound healing

Database	Controlled descriptors	Non-controlled descriptors
MEDLINE	Photochemotherapy	Photodynamic Therapy
	Wound healing
	Wounds and Lesions	Sores
LILACS	Photochemotherapy	Photodynamic Therapy
	Wound healing
	Wounds and Lesions	Sores