Autologous Regenerative Technology (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. The latter may cause
morbidities such as risk of infection, discoloration, pain, and scarring of both donor and
recipient areas. Full-thickness stin 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.
Split-thickness skin grafting (STSG) has been used to close large skin wounds, 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. Nevertheless, because deep dermal
structures such as 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. Other limitations include
healing of the donor site, which often is delayed and leaves unappealing pigmentary changes
and, at times, scar formation.

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. 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.

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. This principle became clear when fractional
photothermolysis (FP) was developed that is currently used for photoaged skin treatment and
wound scars. 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. 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.

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. The ART
may provide a more effective method of harvesting skin with minimal or no pain, healing
rapidly with little scarring. This can take place in an outpatient setting, with the use of
only local anesthesia.

Inclusion Criteria:

- Any age ranging 18-90, any gender or ethnic background is a candidate.

- Subjects with chronic wounds that have been present for at least 4 weeks

Exclusion Criteria:

- Pregnant women.

- 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).