Prospective Clinical Trials on Skin Wound Healing in Young and Aged Individuals
Condition: Age; Cicatrix, Hypertrophic; Fibrosis; Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Hypertrophy; Cicatrix; Cicatrix, Hypertrophic
Study type: Observational

Summary: 
      Regular wound healing follows a well-ordered sequence of overlapping phases: inflammation,
      proliferation, maturation and remodelling.

      In the young, damage to an organ mostly triggers fully regenerative mechanisms called
      "primary" wound healing. Repeated damage in young individuals may cause "secondary" wound
      healing eg. scar formation reflecting a rescue program, in which reorganisation has failed.

      Organ failure in the ageing organism is characterized by a progressive loss of its capability
      to achieve an orderly reactivation of organ repair, and results in a combination of chronic
      inflammation and fibroproliferative, non-regenerative repair affecting several organs,
      including lung, liver and skin.

      RESOLVE's objective is to identify, characterize, and validate molecular targets responsible
      for shifting primary organ repair towards fibroproliferative wound healing as a result of an
      age-dependent loss of regulatory control.

      The structured approach is based on

        -  different forms of wound healing,

        -  different human diseases and

        -  different genetic backgrounds,

      aiming to provide future diagnostic tools in various organs, to create transgenic animal test
      systems, and to identify molecular targets involved in fibroproliferative wound healing.
    

Detailed description: 
      Cutaneous scars are frequently encountered conditions. The process of wound repair, however,
      is complicated, and various factors contribute to different types of scarring (eg.
      hypertrophic, atrophic).

      WP 2.1: Regular skin repair

      In elective plastic surgery most excised operative skin specimens are usually discarded, and
      represent an excellent opportunity of harvesting skin biopsies without additional invasive
      measures. This work package analyzes skin samples of individuals after elective plastic
      surgery with normal wound healing serving as control group.

      WP 2.2: Skin repair with and without hypertrophic scar formation

      A classic example of fibroproliferative repair in the skin is hypertrophic scarring
      classified as a dermal skin lesion, which is raised above skin level, stays within the
      confines of the initial wound and increases in size by pushing out the margins of the scar
      without invading the surrounding normal tissue.

      Hypertrophic scarring is a condition commonly observed after burns and in regions of
      prolonged wound healing (>21 days). The underlying pathology of hypertrophic scarring,
      however, is poorly understood. Hypertrophic scars can be managed conservatively, and only
      require surgical intervention under special circumstances.

      This work package analyzes the clinical and molecular response to a standard treatment
      regimen in skin regions with and without hypertrophic scars after skin injuries.

      WP 2.4: Wound healing in normal and diabetic individuals

      Diabetes mellitus is a known factor to cause impaired wound healing. Due to microangiopathic,
      macroangiopathic and other conditions resulting from atherosclerosis and peripheral
      neuropathy wound healing in diabetic individuals is usually delayed (hypotrophic, atrophic)
      and often complicated by immunosuppression and superinfections. The rising prevalence of
      diabetes mellitus in the elderly population makes it necessary to understand its related
      processes in relevant clinical wound models.

      Split-thickness skin-grafting is a commonly applied technique in plastic surgery, and donor
      sites of previously uninjured skin regions spontaneously heal within two weeks, representing
      an ideal condition to monitor clinical and molecular changes in diseased vs. non-diseased
      states.

      This work package analyzes skin repair in donor sites of split-thickness skin grafts in
      non-diabetic and diabetic individuals.
    

Intervention name(s): Skin sample; Skin biopsy; Skin biopsy; Blood taking; Blood taking
Intervention type(s): Other; Other; Other; Other; Other
Intervention description(s): Taken from regularly discarded tissue during routine operation; Skin biopsy from regions exhibiting normal and/or hypertrophic scarring at day 0 and day 90; Biopsy from skin graft harvest site during routine operation on day 0 and follow-up on day 90; Blood taking on day 0; Blood taking on day 90
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        WP 2.1 Individuals due for planned elective plastic surgery with regular wound healing

        WP 2.2 Individuals, who suffered from burns, trauma or having undergone any type of
        previous surgery with and without hypertrophic scar formation

        WP 2.4 Individuals, who require split-thickness skin grafting for skin defects with or
        without diabetes mellitus
      
Biospecimen description: 
      Skin biopsy Blood samples
    
Keywords: wound healing; hypertrophic scar; skin transplantation; diabetes mellitus