2.2.2.3　Pathologic skin scars

Skin scar is the change of skin tissue morphology and histopathological features caused by trauma.According to the statistics，it is estimated that there are more than one hundred million new cases of scar patients annually in developed countries.Skin scar causes the changes of appearance and function，affects the mental health of patients and reduces the quality of life of patients.Pathologic skin scars includes hyperplastic scar，keloid，atrophic scar，and the scar cancer，etc.

The pathogenesis of skin scar has not been fully elucidated，and the pathogenesis differs among different kinds of skin scars（Figure 2-8）.It has been widely accepted that abnormal proliferation and differentiation of fibroblasts and deposition of extracellular matrix are the central parts of the disease.These processes mainly involve TGF-β，inflammatory cytokines and MMP family，etc.In addition，mechanical force related signaling pathway is also thought to play an important role in regulating the formation of skin scar.

There are various therapies for treating scars，which can be divided into five categories：①surgical resection；②intrascar injection，including botulinum toxin A，bleomycin，glucocorticoid and 5-fluorouracil（5-FU）；③electro-optical technology treatment，including dot matrix laser，pulsed dye laser，radiofrequency ablation and intense pulsed light；④topical drugs，including onion extract，mitomycin C and imiquimod；⑤physical therapy，including silicone gel pressure therapy，cryotherapy，radiation therapy and microneedle therapy.The choice of therapies is closely related to the type of scar，the patient's previous treatment history and the patient's compliance.

Surgical resection can treat keloid alone.However，due to the recurrence rate of keloid is as high as 40％-100％，surgical resection is usually combined with radiotherapy，frozen therapy，silicone gel and intrascar injection.There are several types of injection drugs，such as glucocorticoid，bleomycin，5-fluorouracil，rapamycin，verapamil，doxorubicin，botulinum toxin A and tretinoin.Among them，5-fluorouracil，bleomycin and glucocorticoid have been supported by clinical studies.

Due to the possibility of oncogenicity，radiation therapy is usually not recommended as the first-line treatment，but for the refractory keloid and hyperplastic scar.Radiation therapy could induce fibroblast apoptosis and gene mutation，and damage the stem cell of connective tissue.Striping laser（Er：YAG laser，CO2 laser），intense laser and pulsed dye laser（585 nm and 595 nm），etc.，has been studied in clinical trials.(https://www.daowen.com)

The mechanism of cryotherapy for skin scar is that low temperature cause the damage of cells through the rapidly cooling of refrigerant（usually liquid nitrogen）and blood stasis after thawing damage the scar tissue.In addition，frozen can make patients numb，reduce the pain and increase the compliance of treatment.

Commonly used topical drugs include onion extract，mitomycin C and imiquimod.Onion extraction is commonly used in preventing scar formation or as the adjunct therapy.Onion extraction can inhibit the proliferation of fibroblasts and mast cells，reduce inflammation，and prevent scar formation.Clinical trials of mitomycin C in treating hyperplastic scar are insufficient and lack of evidence.Imiquimod is used for the recurrence of auricular keloid.

The mechanism of microneedle in treating skin scar is unclear.Some scholars believe that the moderate inflammatory response after microneedle therapy can activate MMPs，degrade the collagen fibers with abnormal arrangement and remodel the skin tissues.Besides，it is considered that microneedle can affect the gap-junction protein，change the mechanical force of fibroblasts，so as to intervene the production of collagen and secretion of cytokines.The change of membrane potential after exposure to microneedle improves the viability of cells，promotes the production of protein，potassium and growth factors，stimulates the migration of fibroblasts to the injured area，and increases the production of collagen，elastin and proteoglycan.