Skin Repair
This article was originally published in Start Up
Executive Summary
A handful of start-ups hopes to fill the cracks in the fragmented market for skin repair. Their approaches vary widely; British start-up Renovo has a pharmaceutical approach to the prevention of scarring. Reconstructive Technologies believes that the best replacement for skin is skin itself; it has developed a bioreactor that accelerates the growth of autograft skin, with both {in vivo} and {in vitro} systems. Artecel Sciences will use adipose-derived stromal cells in cosmesis and hematopoietic support. Niadyne 's platform of unique formulations of niacin lend themselves to a variety of applications, in cosmeceuticals and in cardiovascular disease.
Starting at the surface
In wound care, investors are once burned and twice shy. The hype and excitement that has surrounded tissue engineering for the past 20 years has given way to wariness and suspicion. No single product has been able to cut much of a swathe in the potential $1 billion skin replacement market, although dozens of companies have tried for years with both non-living and living approaches. After years of development, Advanced Tissue Sciences Inc. is still struggling to get FDA approval for its dermal replacement product for its first indication in diabetic foot ulcers. Sales of Organogenesis Inc. are beginning to ramp up—the company reported that in 2000 it sold 12,685 units of its bi-layered living skin replacement Apligraf (marketing partner Novartis AG gets end revenues [See Deal]), the only product approved for venous stasis ulcers and diabetic foot ulcers. But longer term, Apligraf could easily face competition from a less finicky product. Its shelf life is only five days from the date of packaging, which frequently leaves physicians only 72 hours in which to use it. Sales of early market entrant Integra LifeSciences Holdings Corp. —which has a non-living collagen based dermal replacement product—are still modest due to the scope of its FDA approval, which limits the product to the relatively small number of patients with severe burns. The company only recently enlisted the aid of Johnson & Johnson 's Ethicon Inc. , a marketing partner that has the wherewithal to tackle this fragmented market.
The market for skin repair products is complicated; issues of the skin are handled by a wide variety of practitioners—plastic surgeons, vascular surgeons, podiatrists, dermatologists, diabetes doctors, and primary care physicians. Wounds are often a manifestation of some other underlying condition, a fact that not only makes wound care marketing difficult, but also confounds scientific approaches and clinical trials. It is still early in researchers' understanding of the wound healing process. While today, the industry tends to characterize patients in terms of acute wounds—that is, excisional wounds or burns in an otherwise healthy patient, or chronic non-healing wounds of four or five types due to various underlying pathologies, in reality, there is a great deal more patient variability. Academicians are just now beginning to look at gene arrays of non-healing and healing wounds to better characterize the process. British start-up Renovo Ltd. is taking stock of individual responses to wounding. It is conducting pharmacogenomic analyses on cells taken from wound sites to substantiate the observation that severity of scarring varies by race, for example. Renovo is also unique in its focus on the prevention of scarring, which not only causes cosmetic problems but can also lead to functional deformities; peritoneal scars, for instance, can cause infertility.
In adults, the regenerative process of early healing rapidly gives way to the overproduction of collagen that causes scarring. One industry expert likened this fibrotic process to quickly boarding up a fence by nailing boards every which way, rather than reconstituting the fence picket by picket. Scarring does not occur in embryos or fetuses, a phenomenon that led Renovo to identify various types of TGF beta that were differentially expressed between adults and fetuses. The company is developing drugs to neutralize the actions of these growth factors in scarring.
Reconstructive Technologies Inc. (RTI) chooses to skirt around the unknowns of wound healing, focusing instead on a method of increasing the supply of natural, autograft skin for burns and reconstructive surgery. The company believes that skin replacement products that incorporate only selected components of skin will be limited in their applicability. The company has developed a bioreactor that, by bathing skin in nutrients while stretching it, has been able to triple the size of a starting sample in six days. As an autologous therapy requiring off-site culturing time, the therapy may face the same market resistance that Genzyme Tissue Repair's (now Genzyme Biosurgery ) Carticel autologous cartilage repair strategy and its Epicel epidermal autografts have encountered, but RTI hopes that speed will give it an advantage. Meanwhile, the company has partnered with plastic surgery firm Inamed Corp. , to improve an existing skin expansion procedure.
Like many tissue engineering companies, Artecel Sciences Inc. begins with a platform of adipose-derived stromal cells that could be brought to bear against a variety of applications in regenerative medicine, but it has decided to avoid the vagaries of reimbursement and turn its focus first to cosmetic surgery, an approximately $10 billion market in the US. It will culture adipose-derived stromal cells into fat cells, which it can inject into wrinkles, scars and other cosmetic flaws. Long-term, it will tackle some unmet clinical needs in bone and cartilage repair and as well as hematopoietic support for bone marrow transplantation.
Niadyne Inc. hopes to affect the health of skin at the nutritional level. It has developed a proprietary dermal delivery method for the vitamin niacin, to enhance the appearance of skin. It too is starting in a market financed by consumers, the $2.3 billion US cosmeceuticals market, but intends to move into other therapeutic areas with compounds for wound healing and heart diseases.
Whatever the approach, the markets for skin repair are large and growing. The number of people over the age of 65, a population that is prone to disorders caused by skin exposure, diabetic ulcers, venous stasis ulcers, and pressure sores, is going to double between 2000 and 2030, say statisticians, and they will be living longer than in the past. Fortunately, as researchers increase their understanding of the regenerative powers of tissue at the molecular level, new therapies should emerge.