Background. Chronic and recalcitrant wounds present a significant therapeutic challenge. Amniotic tissues contain many regenerative cytokines, growth factors, and extracellular matrix molecules including proteoglycans, hyaluronic acid, and collagens I, III, and IV. Dehydrated amnion/chorion grafts are currently used to treat a variety of wounds such as diabetic foot ulcers and burns. Objective. The investigators hypothesized that processing methodologies, dehydration, and hypothermic processing and storage of amniotic tissues would affect overall quality of wound healing; they compared dehydrated amnion/chorion (dHACM) grafts to a novel hypothermically stored amniotic membrane (HSAM) graft in a full-thickness rat wound model. Materials and Methods. Sprague-Dawley rats were anesthetized and prepped for surgery; four 1.5-cm diameter full-thickness wounds were created and treated with either: (1) dHACM, (2) dHACM meshed, (3) HSAM, or (4) wound left ungrafted (sham). After 9 or 21 days, wounds and surrounding areas were collected and stained with hematoxylin and eosin. Blinded quantitative analysis of quality of wound healing was completed by evaluating hair follicle/gland formation, dense/scar-like matrix, and basket-weave matrix. Results. At varying time points following placement of the grafts into full-thickness defects, the authors found that all amniotic-derived tissue grafts appeared to stimulate improved healing over sham wounds, evidenced by more normal-appearing dermal matrix architecture, epidermal structure, and maturity. In addition, the HSAM grafts promoted greater tissue regeneration than the dHACM meshed grafts, as measured by the presence of basket-weave collagen matrix and formation of follicles and glands. Conclusions. In sum, this study builds on the amassing literature supporting amniotic tissues for wound repair and demonstrates the importance of tissue processing on the quality of wound healing.