Purpose: Although traditional and current treatment strategies may demonstrate success, persistence or recurrence of difficult-to-heal wounds remain significant problems. A novel product, Hyalomatrix$^{(R)}$ (Fidia Advanced Biopolymer, Abano Terme, Italy) is a bilayer of an benzyl esterified hyaluronan scaffold beneath a silicone membrane. The scaffold delivers hyaluronan to the wound, and the silicone membrane acts as a temporary epidermal barrier. We present the results obtained with Hyalomatrix$^{(R)}$ in the treatment of difficult-to-heal wounds. Methods: From November, 2008 to March, 2010, Hyalomatrix$^{(R)}$ has been used on total 10 patients with wounds that were expected difficult to heal with traditional and other current strategies. After average 37.4 days from development of wounds, Hyalomatrix$^{(R)}$ was applied after wound debridement. On the average, Hyalomatrix$^{(R)}$ application period was 17.6 days. After average 16.5 days from removal of Hyalomatrix$^{(R)}$, skin grafts was performed. Results: In all cases, regeneration of fibrous granulation tissues and edge re-epithelization were present after the application of the Hyalomatrix$^{(R)}$. And all of the previous inflammatory signs were reduced. After skin grafts, no adverse reactions were recorded in 9 cases. But in one case, postoperative wound infection occured due to a lack of efficient fibrous tissues. In this model, the Hyalomatrix$^{(R)}$ acts as a hyaluronan delivery system and a barrier from the external environments. In tissue repair processes, the hyaluronan performs to facilitate the entry of a large number of cells into the wounds, to orientate the deposition of extracellular matrix fibrous components and to change the microenvironment of difficult-to-heal wounds. Conclusion: Our study suggests that Hyalomatrix$^{(R)}$ could be a good and feasible approach for difficult-to-heal wounds. The Hyalomatrix$^{(R)}$ improves microenvironments of difficult-to-heal wounds, reduces infection rates and physical stimulus despite of aggravating factors.