**4. Photodynamic therapy and wound healing**

Photodynamic therapy (PDT) as a photochemistry process can kill cancer cells, inactivate infected pathogens, and demolish target tissue. In PDT process, one special material called photosensitizer or nontoxic dyes absorbs visible light and produces excited singlet state such as singlet oxygen and hydroxyl radicals that are able to attack to target cells [21]. Administra‐ tion of photosensitizer either topically or systemically in combination with irradiation appropriate wavelength laser is a promising treatment modality in wound healing especially for chronic pressure and decubitus wounds frequently encountered in diabetic and disable patients. The healing of chronic wounds and venous stasis ulcers of the leg is compromised by infection, yet PDT has an antimicrobial action [22]. Bacterial burden in chronic ulcer decreases by treatment with infrared radiation. A radiation via endogenous protoporphyrin (and/or protoporphyrin IX [PpIX] of bacteria) is virtually similar to a mild PDT [23]. It appears that PDT with suitable PS together with suitable laser parameters represents effective treat‐ ment modalities in promoting wound healing. PSs associates with three main groups of agents: azine dyes, macrocyclic dyes, and metallated derivatives [24–27]. An extensive range of PSs from different groups including azines, porphyrins, phthalocyanines, and chlorophyll derivatives have been described in eradication of many pathogens such as a variety of bacteria, parasites, viruses, and fungi [22].

Several types of first- and second-generation PSs have been used at minimal doses with laser irradiation performed at wavelengths ranging from 630 to 690 nm, and showed that PDT of acute wounds can lead to an improvement of healing outcomes. Interestingly in one study, the healing of skin flaps after being subjected to ischemia was impaired by PDT treatment, although only one PS (Photofrin) was tested. Further animal model and human wound studies are required to find the main process of enhancement of reepithelization and granulation tissue formation with PDT.

In photodynamic therapy, irradiation of cells with low dosage or small energy may incite proliferation. In using PDT clinically, it is essential to use the suitable doses of both the PS and the activating light source in order to achieve cell death for cancer therapy, or regeneration for wound healing [23]. The newest generations of PSs allowing a faster clearance time of normal tissues are more selective for tumor cells. Although PDT may be nontraumatic but in comparison with nature of lower laser therapy it is almost always traumatic and can cause burns, swelling, pain, and scarring in nearby normal tissue [28].
