Medical Products From Unique Biomaterials

PPTI is focused on developing products to improve medical and surgical outcomes, based on an extensive portfolio of proprietary biomaterials. Biomaterials are materials that are used to direct, supplement, or replace the functions of living systems. The interaction between materials and living systems is dynamic. It involves the response of the living system to the materials (e.g., biocompatibility) and the response of the materials to the living system (e.g., degradation). The requirements for performance within this demanding biological environment have been a critical factor in limiting the myriad of possible metal, polymer, and ceramic compositions to a relatively small number that to date have been proven useful in medical devices.

The goal of biomaterials development historically has been to produce inert materials – materials that elicit little or no response from the living system. However, the Company believes that such conventional biomaterials are constrained by their inability to convey appropriate messages to the cells which surround them -- the same messages that are conveyed by proteins in normal human tissues.

PPTI's Biomaterials Strategy

The products targeted for development by PPTI are based on a new generation of biomaterials which have been designed to be recognized and accepted by human cells, to aid in the natural process of bodily repair (including the healing of tissue and the restoration or augmentation of its form and function), and, ultimately, to promote the regeneration of tissues. The Company believes that the successful realization of these properties will substantially expand the role that artificial devices can play in the prevention and treatment of human disability and disease, and enable the culture of native tissues for successful reimplantation.

Through its proprietary core technology, PPTI produces high molecular weight polymers that can be processed into a variety of material forms such as gels, sponges, films, and fibers, with their physical strength and rate of resorption tailored to each potential product application. These polymers are constructed of the same amino acids as natural proteins found in the body. The Company has demonstrated that its polymers can mimic the biological and chemical functions of natural proteins and peptides, such as the attachment of cells through specific membrane receptors and the ability to participate in enzymatic reactions, thus overcoming a critical limitation of conventional biomaterials. In addition, materials made from PPTI's polymers have demonstrated excellent biocompatibility in a variety of feasibility studies.

PPTI's Biomaterials Technology Platform

PPTI's patented core technology enables messages that direct activities of cells to be precisely formulated and presented in a structured environment similar to what nature has demonstrated to be essential in creating, maintaining and restoring the body's functions. The Company's protein polymers are made by combining the techniques of modern biotechnology and traditional polymer science. The techniques of biotechnology are used to create synthetic genes which direct the biological synthesis of protein polymers in recombinant microorganisms. The methods of traditional polymer science are used to design novel materials for specific product applications by combining the properties of individual "building block" components in polymer form.

In contrast to natural proteins, either isolated from natural sources or produced using traditional genetic engineering techniques, PPTI's technology results in the creation of new proteins with unique properties. PPTI has demonstrated its capability to create materials that:

• combine properties of different proteins found in nature;
• reproduce and amplify selected activities of natural proteins;
• eliminate undesired properties of natural proteins; and
• incorporate synthetic properties via chemical modifications.

Silk-Elastin Polymers

PPTI's primary products under development are based on protein polymers combining selected properties from two of the most extraordinary structural proteins found in nature: silk and elastin.

	Silk, based upon its crystalline structure, has long been known as an incredibly strong material, and has a long history of medical use in humans as a material for sutures.
	Elastin fibers are one of the most remarkable rubber-like materials ever studied. Found in human tissues such as lungs and arteries, elastin fibers must expand and contract over a lifetime, and can be extended nearly three times their resting length without damaging their flexibility.

Despite the incredible individual properties of silk and elastin, neither of these natural protein materials is capable of being processed into forms other than what nature has provided without destroying their valuable materials properties. However, PPTI's proprietary technology has enabled the creation of polymers that combine the repeating blocks of amino acids responsible for the strength of silk and the elasticity of elastin. By precisely varying the number and sequence of the different blocks in the assembled protein polymer, new combinations of properties that the Company believes will be of substantial value in developing new medical products have been created.

Self-Assembling Hydrogels

Protein polymers consisting entirely of silk blocks are insoluble in water and spontaneously precipitate from aqueous solutions. Formation of the precipitate is consistent with the formation of extensive hydrogen bonding between strands of silk-like protein. Elastin blocks have been shown to be flexible units of protein structure. By using the elastin blocks to interrupt and reduce the total crystallinity of protein polymers containing only silk blocks, silk-elastin polymers which are initially water-soluble and then spontaneously and irreversibly self-assemble into gels, under physiological conditions and having a very high water content, were created.

Silk-elastin polymer solutions can be mixed directly with other compounds such as drugs. The solutions are fluid and can be injected through fine gauge hypodermic needles. With time, depending on the specific polymer block structure, the solutions form firm, solid gels that are no longer water-soluble. The rate of gelation is influenced by the polymer composition, concentration, temperature, and other solution conditions. Gelation occurs without the need for chemical cross-linking, therefore no chemical changes occur to the polymer or to any compound or drug that might be incorporated in the polymer solution. These self-assembling hydrogels are the platform upon which PPTI is developing its products for urology and cosmetic applications.

Chemically Cross-linked Adhesives

The development of an adhesive requires polymer molecules that strongly bind both to themselves and to the materials on which they are applied. The use of chemical cross-linking agents which react with both protein polymers and proteins found in the body’s tissues allows for the development of tissue adhesives and sealants. However, such cross-linking agents are not inherently biocompatible because of their reactivity towards tissue proteins. Therefore, the development of a safe and effective tissue adhesive or sealant product requires maximizing adhesive strength while minimizing the amount of cross-linking agent required.

With natural proteins such as fibrin, collagen, and albumen, the basis for several commercially available tissue adhesives and sealants, the adhesive system must be developed within the constraints of the polymer composition nature provides. PPTI’s adhesive systems are based on silk-elastin polymers specifically designed and created for use in adhesives and sealants within the body. These silk-elastin polymers contain periodic elastin-like blocks which have been modified to contain the amino acid lysine, which is reactive towards a variety of cross-linking agents. Important features which distinguish these reactive silk-elastin polymers from natural proteins are 1) the number and regular spacing of chemical sites available for cross-linking (related to adhesive strength), 2) the reactivity of these chemical sites which allows for efficient cross-linking under physiological conditions (related to adhesive strength and minimizing cross-linker use), and 3) the elasticity of the polymer and – correspondingly – the cross-linked polymer matrix.

Additional Protein Polymers

PPTI has also created protein polymers based on repeating blocks of amino acids found in two other classes of structural proteins found in nature: collagen and keratin.

	Collagen is the principal structural component of the body, found in some shape or form in virtually every tissue, ranging from shock-absorbing cartilage to light-transmitting corneas. The defining characteristic of collagen is a triple-helix structure formed by the assembly of three identical molecular chains.
	Keratin is a major component of hair, nails and skin. Its rope-like structure is based on the alpha helix, cross-linked into bundles.

The development of materials based on these polymers is at an early stage of research. The Company has also identified numerous additional natural proteins constructed of repeating amino acid sequences that provide a library of "building blocks" for future polymer, materials, and medical product development.