HAMBURG, Germany - Artificial skin is becoming a hot topic in Germany. By the end of last year, two biotech companies active in tissue engineering announced the launch of products to treat diabetic venous leg ulcers, burns and other skin wounds.

Two million people in Germany suffer from chronic wounds, about 150,000 of them diabetics with venous leg ulcers, a serious and debilitating condition that occurs on the lower leg and is caused by venous insufficiency. According to an industry report by Wedbush Morgan Securities, chronic skin wounds are a $7 billion annual market worldwide, while acute wound treatment amounts to $2.6 billion.

Now, two tissue engineering companies have entered the German market with tissue derived from skin or hair follicle cells of the patients.

BioTissue Technologies, of Freiburg, Germany, has developed BioSeed S, an artificial skin replacement derived from the patient's own cells. For treatment, first a small amount of skin (1 square centimeter) is grafted, from which epithelial cells are cultivated and then suspended in a gel-like fibrin glue matrix. After 18 days, the gel containing noncontact-inhibited and actively proliferating single cells is delivered to the patient's doctor and can be applied like an ointment. After treatment the cells proliferate, resulting in a complete re-epithelization within one to two weeks.

"Around 80 patients have been treated with BioSeed S and in all cases we have seen very favorable results," Eszter Tanczos, chief scientific officer of BioTissue, told BioWorld International. "BioSeed S can close wounds quite deep and heal sores that haven been open for several years in diabetics."

The product is suited to treat second- and third-degree burns as well, he said. "We have even been able to save the life of patients whose skin had been burned to more than 80 percent."

BioTissue was founded as a spin-off of the University of Freiburg in 1997. "We were able to finance the company without any venture capital," Rainer Seubert, CEO of BioTissue, said. "Around DM8 million (US$4.1 million) has been raised from private investors, silent partners and public-law credit institutions."

Seubert added, as the development of additional products was ahead of schedule, BioTissue was now preparing a second financing round: "We want to expand to international markets. The timing seems to be right. Private investors are very interested in participating in the company."

Tanczos said BioTissue is developing tissue engineering solutions to treat pigment anomalies, and to replace oral mucosa, cartilage and bone. "We offer our services and our production facilities including a clean room as a platform for research groups active in tissue engineering. We provide support in terms of GMP production and bringing applications to the market."

BioTissue is part of the Valley Tissue Engineering Center (TEC), a network of universities and biotech companies in the Freiburg "BioValley" region employing 50 scientists and technicians. TEC is funded by the federal state of Baden-W|rttemberg with DM5.5 million.

Another biotech company, BioCare, of Leipzig, Germany, has developed a method to grow artificial skin from the cells of hair roots. Patients have to sacrifice 50 to 100 hairs, including roots, for the method. After cultivation for 30 days a sheet consisting of epidermal cells is delivered to the patient's doctor. The sheets can be patched onto open sores. The method has been developed in cooperation with researchers from the University of Basel, Switzerland.

"As a next step, we are trying to improve the method so that we can grow an artificial skin that is able to cover large areas," Sabine Kr|ger, head of marketing at BioCare, told BioWorld International. "We want to widen the scope of applications. As a next product we plan to add thrombocytic growth factors." The company employs a staff of 15 and was founded without venture capital.

The third product, for which marketing started in Switzerland this month, is Apligraf from Novartis Pharma AG. Apligraf is an artificial skin developed by Organogenesis, of Canton, Ma., and has been on the North American market since 1997. Novartis bought the exclusive international marketing rights for up to $40 million recently. Apligraf is developed from foreskin tissue of newborns, which guarantees perfect immunobiologic compatibility. In contrast to other products, Apligraf has two primary layers, including an outer, epidermal layer of living human keratocytes and a dermal layer consisting of living fibroblasts.

Before the European market is fully accessible for the new products, one major obstacle has to be overcome: In their regulation bureaucracy, some European countries regard artificial skin as a transplant, while others consider it a drug or a medicinal product, just like dressing material. In Germany, the facilities and the process for the production of homologous artificial skin have to be certified by the authorities. After that, no additional approval is necessary.