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.

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.

WP2.1

Inclusion Criteria:

• age 18-45 and 55-85 years, respectively

Exclusion Criteria:

• past medical history of hypertrophic scarring or keloid disease
• cardiac disease adversely affecting peripheral blood flow
• active neoplastic disease
• immunosuppressive condition, congenital or acquired
• anemia
• autoimmune disorder
• acute or chronic renal failure
• liver cirrhosis or active hepatitis
• active substance-abuse disorder
• severe underweight (body mass index <16)
• endocrinological disorder
• pregnancy or lactation for women of child-bearing age

WP2.2

Inclusion Criteria:

• age 18-45 and 55-85 years, respectively
• normal and/or hypertrophic scars
• Baux score <100

Exclusion Criteria:

• sepsis
• electrical and/or chemical burn
• clinically significant wound infection in areas of planned biopsies
• cardiac disease adversely affecting peripheral blood flow
• active neoplastic disease
• immunosuppressive condition, congenital or acquired
• autoimmune disorder
• acute or chronic renal failure
• liver cirrhosis or active hepatitis
• active substance-abuse disorder
• severe underweight (body mass index <16)
• endocrinological disorder
• pregnancy or lactation for women of child-bearing age

WP 2.4

Inclusion Criteria:

• age 18-45 and 55-85 years, respectively

Exclusion Criteria:

• cardiac disease adversely affecting peripheral blood flow
• active neoplastic disease
• immunosuppressive condition, congenital or acquired
• anemia
• autoimmune disorder
• acute or chronic renal failure
• liver cirrhosis or active hepatitis
• substance-abuse disorder
• severe underweight (body mass index <16)
• thyroid function disorder
• pregnancy or lactation for women of child-bearing age

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