Neogenesis of Full-thickness Skin and Concomitant Dermal Appendages in Acute Wounds Using Novel Autologous Homologous Skin Construct Therapy in Preclinical and Clinical Settings

Introduction: Many acute wounds incur successive complications and the encumbrance on public health is increasing significantly. More than $12 billion is spent on patient management of acute wounds refractory to standard of care therapies. Conventional treatments of cutaneous wounds, including skin grafting and advanced dressings, are limited by graft failure, scarring, contraction, and incomplete healing. A novel approach using an autologous homologous skin construct (AHSC) was evaluated for full-thickness skin regeneration and wound closure in acute injuries in a pre-clinical model and clinical case.

Methods: Full-thickness wounds on 12 Yorkshire swine dorsa were treated with AHSC or conventional dressings. Healing was examined with digital and stereoscopic imaging for 6 months. Histological analysis was evaluated by brightfield, confocal, and scanning-electron-microscopy. Molecular composition of wounds was measured with Raman microscopy. Gene expression between AHSC/STSG/native skin were analyzed using stem cell and extracellular-pathway-PCR-arrays. A 70yo male with an acute left lateral malleolus wound refractory to conventional treatments and an acellular xenogenic skin substitute was treated with AHSC. A small abdominal full-thickness skin harvest was sent for AHSC manufacturing, applied to the wound-bed within 48-hours, and dressed like a conventional skin graft. Wound closure was assessed with digital photography for 6 months. 

Results: Preclinical AHSC-treated wounds demonstrated improved healing, decreased contracture, and development of hair follicles and dermal appendages on macroscopic and fluorescent imaging. AHSC-treated skin was similar to native skin in collagen and keratin Raman spectra (R2=0.95), and stiffness and elasticity (p<0.05). AHSC-treated wounds showed upregulated gene expression compared to native tissue. Imaging confirmed AHSC-treated wounds had similar morphology, organization, and nuclear content to native skin. The patient treated with AHSC experienced complete wound closure, minimal lower-extremity skin contracture, ambulated without difficulty, and no donor-site complications. 

Conclusion: AHSC-therapy was efficacious in regenerating full-thickness skin in an acute injury preclinical model and clinical case.