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Significance: Opioid use disorder and transition to injection drug use (IDU) are an urgent, nationwide public health crisis. Wounds and skin and soft tissue infections (SSTIs) are common complications of IDU that disproportionately affect people who inject drugs (PWID) and are a major source of morbidity and mortality for this population. Critical Issues: Injections in a nonsterile environment and reusing or sharing needles facilitates bacterial inoculation, with subsequent risk of serious complications such as sepsis, gangrene, amputation, and death. PWID are susceptible to infections with a wide spectrum of organisms beyond common culprits of SSTI, including Clostridium and Bacillus spp., as well as Candida. Recent Advances: Syringe services programs (SSPs) are cost-effective and successful in reducing harms associated with IDU. SSPs provide new equipment to PWID and aid in discarding used equipment. SSPs aim to reduce the risks of unhygienic injecting practices, which are associated with transmission of infections and blood-borne pathogens. Future Directions: Concurrently run SSPs and wound care clinics are uniquely positioned to facilitate care to PWID. Providing new, sterile equipment as well as early wound care intervention can reduce morbidity and mortality as well as health care expenditures by reducing the number of SSTI and injection-related wounds that require hospital admission. Establishment of wound care clinics as part of an SSP represents an untapped potential to reduce harm.

Significance: Transforming growth factor β (TGFβ) has a crucial role in maintaining skin homeostasis. TGFβ signaling is important for re-epithelialization, inflammation, angiogenesis, and granulation tissue formation during wound healing. This review will discuss the most important findings regarding the role of TGFβ in epidermal maintenance and its restoration after injury. Recent Advances: Latest findings on the role of TGFβ signaling in normal and impaired wound healing, including the role of TGFβ pathway in tissue regeneration observed in super-healer animal models, will be reviewed. Critical Issues: The TGFβ pathway is attenuated in nonhealing wounds. Observed suppression of TGFβ signaling in chronic ulcers may contribute to the loss of tissue homeostasis and the inability of keratinocytes to migrate and close a wound. Future Directions: A better understanding of TGFβ signaling may provide new insights not only in the normal epithelialization process, but also in tissue regeneration. Future studies f...

Significance: Keratinocytes, a major cellular component of the epidermis, are responsible for restoring the epidermis after injury through a process termed epithelialization. This review will focus on the pivotal role of keratinocytes in epithelialization, including cellular processes and mechanisms of their regulation during re-epithelialization, and their cross talk with other cell types participating in wound healing. Recent Advances: Discoveries in epidermal stem cells, keratinocyte immune function, and the role of the epidermis as an independent neuroendocrine organ will be reviewed. Novel mechanisms of gene expression regulation important for re-epithelialization, including microRNAs and histone modifications, will also be discussed. Critical Issues: Epithelialization is an essential component of wound healing used as a defining parameter of a successful wound closure. A wound cannot be considered healed in the absence of re-epithelialization. The epithelialization process is impaired in all types of chronic wounds. Future Directions: A comprehensive understanding of the epithelialization process will ultimately lead to the development of novel therapeutic approaches to promote wound closure.