Autologous Regeneration of Tissue (ART) for Wound Healing

Skin wounds sometimes are difficult to heal by primary closure and often require tissue
substitution by autologous grafting requiring harvesting of donor skin [1, 2]. The latter may
cause morbidities such as risk of infection, discoloration, pain, and scarring of both donor
and recipient areas [3].

Full-thickness skin grafts (FTSG) are created when the entire dermis and epidermis are
harvested. These grafts are typically used for acute full-thickness wounds where the wound
can sustain and nourish the graft and improved cosmesis is important [4]. Split-thickness
skin grafting (STSG) has been used to close large skin wounds, [5] and it involves the
harvesting of the epidermis and upper dermis from a donor site. It is generally the preferred
grafting method for restoring the structural integrity of chronic wounds, as the wound bed
may not have the ability to support a FTSG [4]. Nevertheless, because deep dermal structures
such sweat glands and hair follicles are not harvested, the STSG is functionally abnormal.
Before the grafting process takes place, STSGs are commonly meshed and enlarged, increasing
the coverage area and allowing fluid drainage. However, the meshing process produces a
"fish-net" appearance of the grafted skin [1]. Other limitations include healing of the donor
site, which often is delayed and leaves unappealing pigmentary changes and, at times, scar
formation [4].

Currently, engineered "off the shelf" grafts such as cadaveric skin, xenografts, and
artificial skin substitutes are being used in the management of chronic, difficult to heal
wounds. Skin substitutes work by providing cells, growth factors, and other key elements that
promote healing while preventing extracellular matrix degradation [6]. However, these only
offer transient wound coverage, and require secondary healing of the wound itself. Thus,
autologous skin grafting continues to be necessary. Scar formation at the donor and grafted
site remain most troublesome morbidities in autologous skin grafting. Scar tissue is stiff,
dysfunctional, often painful, and tends to contract over time, producing skin irregularities
[7].

In contrast, skin remodeling is a process that substitutes missing tissue while preserving
tissue architecture. While scarring is triggered by large-scale tissue damage, remodeling is
stimulated by microscopic tissue damage [8]. This principle became clear when fractional
photothermolysis (FP) was developed that is currently used for photoaged skin treatment and
wound scars [8, 9]. In FP, laser microbeams are used to produce microscopic thermal injury
per cm2 of skin surface, which causes very thin columns of tissue damage or ablation. It has
been found that columns less than 500 µm in diameter heal promptly without scarring [1, 10].
FP involves full-thickness (i.e. complete epidermis and dermis) tissue injury in which the
epidermis closes within 1 day, and the dermal damage is fixed in around 2 weeks, followed by
tissue remodeling without scarring [9].

Because the experience with FP showed that millions of small, full-thickness columns of skin
tissue can be removed without scarring, it was hypothesized that full-thickness microscopic
skin tissue columns (MSTCs) could be harvested from healthy skin with insignificant donor
site-morbidity and that these MSTCs could function as a graft to accelerate wound healing.

To explore this, a prototype device was developed that can harvest hundreds of full-thickness
columns of skin tissue (500 micrometer diameter) using single-needle, fluid-assisted
harvesting technology. The harvested MSTCs can subsequently be placed directly onto a wound
to aid in healing.

With conventional full thickness grafts and split thickness grafts, the donor area requires
sometimes a period of immobility, requiring attentive wound care and pain management [11].
The ART may provide a more effective method of harvesting skin with minimal or no pain,
healing rapidly with little scarring [1]. This can take place in an outpatient setting, with
the use of only local anesthesia.

Inclusion Criteria:

- Adults from 18 to 90 years of age.

- Patients that have a chronic wound in any area of the body defined as having been
present for at least 30 days of duration.

- Able and willing to give consent for the study.

Exclusion Criteria:

- Pregnant women (Urine hCG test will be performed at baseline on women of child bearing
potential).

- Adults unable to consent.

- Prisoners.

- Subjects requiring concurrent systemic antimicrobials during the study period for any
infection.

- Subjects with leg lesions and clinically significant and unreconstructed peripheral
arterial disease.

- Subjects who are receiving immunosuppressive agents, radiation therapy, or cytotoxic
agents.

- Subjects who require treatment for a primary or metastatic malignancy (other than
squamous or basal cell carcinoma of the skin).

- Subjects with other conditions considered by the investigator to be reasons for
disqualification that may jeopardize subject safety or interfere with the objectives
of the trial (e.g., acute illness or exacerbation of chronic illness, lack of
motivation, history of poor compliance).