By Dr. Aleksandra Ćwil-Kaczmarek And Caroline Lauret, Evonik Health Care

Healthy skin is often considered to represent overall well-being and health. Biomaterial technologies used for treating wounds, scars and to counteract skin aging have progressed rapidly in recent years. Moreover, consumers and patients are more interested in finding sustainable, less invasive solutions to heal their skin. As the main structural protein family in the body, collagen allows autonomous, self- restoration of the skin after injury or damage and can counteract the process of aging.

Collagen contributes between a quarter and one third of total protein mass in humans and other animals. It is totally biodegradable and has a high degree of biocompatibility, making it ideally suited for tissue repair. In therapeutic applications, collagen can be processed to a desired form and applied directly to the skin. Collagen can also be rebuilt by the body’s own cells and the body can be stimulated to produce its own collagen, for example, in the skin.

This article examines two aspects of sustainable skin self-healing: using non-animal-derived collagen for tissue regeneration, and the application of bioresorbable polymer powders to stimulate the body’s natural production of collagen.

Non-animal-derived collagen for wound healing More than 28 types of collagen have been identified to date, each of which has certain properties such as rigidity, shape, and integrity. These collagen types are critical in the formation and functionality of various parts of the body including tissues, skin, cartilage, organs, bone, bone marrow, cell membranes, ligaments, hair, and the lungs.

Thanks to its well-defined structure and how it interacts with cells and tissues, collagen has a wide range of applications. It can be processed directly, or in some cases using additional cross-linking technologies, into a variety of forms such as lyophilized powders, liquid solutions, hydrogels, films or meshes and sponges for use across a wide variety of health care applications.

Collagen in tissue regeneration Collagen is widely used across a range of common orthopedic, cardiovascular, ocular, general surgical, dental, regenerative medicine, and wound care applications. For burn and wound healing, collagen can be applied as a dressing to help stimulate the growth of new tissue. The dressings contain live tissue and are used in direct contact with the wound bed, absorbing discharged matter and hydrating the skin to enhance healing. Chronic wounds are characterized by persistent inflammation, destruction of the extracellular matrix (ECM) and lack of active soluble mediators in the wound healing process. Collagen dressings help to stimulate these processes and can therefore accelerate the healing of chronic wounds.

Collagen without animals Almost all medical and pharmaceutical grade-collagen used today is derived from animal-based sources such as the skin or tendons of cows and pigs. Some collagen is also extracted from marine sources such as fish or jellyfish. For a limited number of R&D activities, collagen is also extracted at extremely small quantities from the human placenta following a child’s birth.

The supply of collagen from traditional animal-based sources has several risks relating to safety, consistent reproducibility, sustainability, and consumer acceptability. There is a risk of pathogen and disease transmission, immunogenic or allergic reaction as well as the issue of sustainability, since harvesting collagen from animals has a significant impact on the environment. Furthermore, many people choose not to consume or use animal products for ethical or religious reasons.

Quality and Reproducibility For many medical and pharmaceutical applications, including wound care, it is critical that collagen can be made using a process that ensures its properties and characteristics are reproducible to enable consistent interaction with cells and tissues. The industrial process to extract, sterilize, purify, and supply traditional sources of collagen in a reproducible manner is extremely challenging and costly. Many healthcare companies and regulatory agencies would favor a source of collagen that provides batch-to-batch reproducibility.

Evonik’s non-animal derived collagen Evonik has developed a unique collagen platform technology that can address unmet market needs for the use of collagen across healthcare and other life science applications. The technology is devoid of all animal and human origin materials and features a triple helix structure that enables it to mimic (and in some cases potentially enhance) the attributes of natural collagen.

This recombinant collagen is also designed to be highly soluble at physiological pH to make it suitable for enhanced cell interaction and adhesion. It is also designed for use with various cross-linking and technologies so that it can be processed into a variety of forms and shapes such as gels, powders, creams, foams, fleece, and sponges, making it especially suitable for wound healing.

The fermentation-based process occurs under precisely defined conditions to enable the creation of collagen with a high level of purity that is reproducible at development or commercial scale. This consistent level of reproducibility and efficient scalability is difficult to achieve with other known collagen sources.

In addition to the production and supply of its collagen in a variety of forms, Evonik also leverages its global application, formulation and manufacturing competencies with biomaterials, drug products and tissue engineering to support customers in the development and commercialization of their own products. These services complement Evonik’s existing core competencies in the development and supply of biomaterials and pharmaceutical drug products, and the production of active pharmaceutical ingredients, advanced foods, and bio-fabricated materials via fermentation-based processes.

Bioresorbable polymer powders used in dermal fillers During the aging process, the face loses fat and volume while the skin loses collagen and elasticity. Dermal fillers, also known as soft tissue fillers, are injected into the skin using a minimally invasive procedure to plump thin lips, enhance shallow contours, soften facial creases, remove wrinkles, and improve the appearance of scars. In contrast to Botox – another popular minimally invasive procedure – dermal fillers do not freeze muscles using purified bacteria, rather they contain ingredients that add fullness to areas that have thinned due to aging.

Dermal fillers help restore volume and augment soft tissue and are often used as an effective complement to facial surgery. The quick procedure produces reliable results and minimal downtime for the patient.

Materials used in dermal fillers Dermal fillers can be based on several different materials including hyaluronic acid, collagen, and bioresorbable polymers such as Poly-L-Lactic acid (PLLA) or Polycaprolactone (PCL). Although collagen fillers can be injected into the skin directly to replace the skin’s natural collagen, the effect does not last as long as other fillers and there can be unwanted or allergic reactions.

Suitable alternatives are PLLA or PCL, which are marketed by Evonik for use in dermal fillers as part of the RESOMER® bioresorbable polymer portfolio. Both are biodegradable, biocompatible, synthetic polymers which have wide use in implantable medical applications like absorbable sutures and bone screws. Used in fillers it is especially long lasting and is administered in a serious of injections over a period of several months. The effects of bioresorbable polymers generally become increasingly apparent over time – typically over several weeks – and these last for up to two years.

Benefits of Bioresorbable Polymer-Based Fillers Polylactic acid-based dermal fillers are a semi-permanent correction procedure that stimulate the body to produce its own collagen. The key benefit of those fillers over other dermal fillers such as those based on hyaluronic acid are their long-lasting effect. After initial treatment with PLLA or PCL-based fillers, the outcome improves over time as the dermal thickness expands, and the positive effects can be seen for up to two years (for hyaluronic acid the effects usually last one year). They are fully biodegradable because they metabolize into water and CO2 over time.

Powders for Dermal Filling The well-established RESOMER® polymers can be milled into a fine powder for use in dermal fillers. With a 30-year track record for efficacy, safety, biocompatibility and supply security, these polymers have been widely used in medical device applications such as for wound healing, orthopedic devices, and cardiovascular devices.

By disintegrating RESOMER® pellets into a GMP-grade bioresorbable powder, RESOMER® can be used successfully in dermal fillers. Evonik developed a unique solvent-free technology for the reduction of the particle size of high molecular weight polymers to use in dermal filler applications.

This powder technology requires no solvent and is compatible with a range of polymers suitable for dermal fillers including PLLA. The particle size distribution is tunable in a range less than 100 micrometers. These powders also adhere to high quality standards: they are made in ISO Class 8 clean rooms, ISO 13485 and GMP compliant, and are suitable for human use.

Interested in More Details? For further information about non-animal-derived recombinant collagen or the RESOMER® powders for dermal fillers, or to request a sample of these products, please get in touch with aleksandra.cwil-kaczmarek@evonik.com or visit our website here.

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About the Authors: Aleksandra Cwil-Kaczmarek is Area Account Manager at Evonik where she is responsible for sales of health care products in Poland, the Czech Republic, Slovakia and the Baltic countries. Her focus is on pharmaceuticals, nutraceutical products and medical devices. Aleksandra holds a PhD in polymer science and chemical engineering from the Polytechnic University of Warsaw in Poland.

Caroline Lauret is Senior Business Manager at Evonik with a wide range of experience in the medical device industry. Skilled in materials science, medical devices, textiles, polymer technology, and global business management, Caroline holds a Master of Science focused on biomedical engineering from Eindhoven University of Technology in The Netherlands.