Photochemical Tissue Passivation Prevents Contracture of Full-Thickness Wounds

Executive summary

Large surface area wounds and full-thickness wounds from burns, trauma, or other injuries, often result in significant scarring and contracture. Wound healing is characterized by different phases that ultimately, and ideally, completely restore tissue function and structure.

However, in many cases, injured tissue is not restored completely, resulting in scarring and contracture of tissue. When contraction and the healing process continue for too long, permanent disfigurement, loss of function, and scarring occur. Healing these large wounds takes a significant amount of rebuilding and time. This results in often disorganized, haphazardly organized, and thin collagen fibers, overactive fibroblasts and myofibroblasts, resulting in contraction, scarring, and abnormal tissue coloring, structure, or function.

This technology, from Dr. William (Jay) Austen, chief of plastic surgery at Massachusetts General Hospital, is systems and methods for improving wound healing of large surface area wounds with less contracture and scarring. Through a photochemical treatment system, called photochemical tissue passivation (PTP), extracellular collagen cross-linking is induced and limits myofibroblast activity. This technology is a novel treatment for wound healing that includes delivering an activating agent to the wound and irradiating the wound with an electromagnetic radiation source.

Unmet need

Large surface area wounds often result in healing that does not restore the function or structure of the original tissue. This is due to scarring and contraction of the skin surrounding the wound.

This technology can prevent contraction, therefore, improving the likelihood of regaining function and structure in the wounded area. This system and method also result in earlier wound maturation and more “normal” tissue production that restores function and structure.

Value proposition

Full-thickness wounds extend beyond the epidermis and dermis into the subcutaneous tissue. There are limited treatment options for these wounds that prevent tissue contracture and reduce scarring.

This technology could be used in the treatment of burns or other trauma. With broad applicability, this technology has the potential to be used in many different contexts around wounds and scar treatment. Notably, the aesthetic, structure and function of the injured tissue could be restored, therefore, reducing the impact that these substantial injuries have on the patient and their recovery.

Technology

Background and proof of concept

The inventors have demonstrated proof of concept in a mouse study. Full-thickness, excisional 1 cm x 1 cm wounds were created on the dorsa of 32 mice. Half of the mice were treated with PTP, and contraction of the tissue was measured over the course of a few weeks. Rose Bengal solution was painted on the wound bed for the treatment group. All wounds were fully healed by the end of the study, but control wounds exhibited almost 20% more contracture by Day 7 and over 80% more contraction by Day 14.

In the control group wounds, a 1.59-fold difference in contracture of the tissue was observed. PTP increased the growth and development of dermal cells, increased vascularity, and appearance of skin appendages earlier and to a greater degree, compared to control wounds.

Advantages

There are limited treatment options for full-thickness wounds that directly address wound contracture. Full-thickness wounds are often treated with controlled hydration dressings, such as hydrocolloids. These dressings often require a second dressing and do not adhere well to the skin. This can lead to discomfort and skin irritation for the patient. Further, these dressings do not prevent skin contracture and do not restore the original function and structure of the injured tissue.

Existing alternatives to this technology that address wound contracture use foreign body scaffolds. Although effective, foreign body scaffolds have varying rates of degradation and tissue integration, which leads to pathologic granulation, failure of scaffold take and appropriate wound healing, and infection risk. PTP is advantageous because its natural crosslinked collagen scaffold prevents pathologic contracture while improving wound healing.

Mechanism

An activating agent is first delivered to the full-thickness wound. The inventors have used Rose Bengal as the activating agent, but it could also be a photosensitizer or photoactive dye. Delivery of the activating agent to the wound could include staining, painting, brushing, injecting, etc. The amount of activating agent depends on the wound, so this therapy is tailored to each patient. The agent is activated through electromagnetic irradiation, which induces crosslinking of the extracellular matrix. This crosslinking process then produces wound healing with less contracture and better matches normal tissue in color, function, structure, and thickness.