OUR STORY

The Reason for the Triple Helix in Our Logo and Why We Use Collagens, Silk, and Hyaluronic Acid in Our Products: A Trio of Excellence

Collagens are protein fibers that can be found in the extracellular matrix of tissue. Most collagens assemble into elongated fibrils and fibers with a defined structure.  However, it is important to mention that not all members of the collagen family do form fibers. Collagens are a major component of skin, tendons, and bone. The mechanical properties of these materials, tendons in particular, are a direct consequence of collagen content and the arrangement of collagen molecules within the scaffold. 

The primary feature of a matured (fibrous) collagen structure is a triple-stranded helix, in which three collagen polypeptide chains are coiled around each other to form a rigid superhelix, strengthening the overall structure. In contrast to most other proteins, collagens show an extraordinarily high proline and glycine content. In addition, selected prolines and lysines of collagen are post-translationally hydroxylated to yield hydroxyproline and hydroxylysine residues. 

These modified amino acids allow tight intermolecular contacts, which enable the collagen triple helix formation. However, collagens are thermodynamically stable once assembled and do not disassemble (due to covalent cross-linking of lysine residues of individual collagen chains). Interestingly, collagen triple helices can further assemble in a highly ordered process resulting in collagen fibrils with specific patterns (Fig. 3), which can even be observed by light microscopy. Silk—a brief introductionAnother remarkable extra-corporal protein fiber is silk. The most prominent silk producers are the caterpillars of the Bombyx mori silk moth since man has harvested their silk cocoons for several thousand years, and silk has found widespread industrial application as a raw material for exclusive fabrics. Similar to insects, spiders also use silk for the protection of their offspring against environmental hazards, and, in addition, many spiders possess a supplementary repertoire of different silk types to construct variously shaped webs to capture prey. Among different shapes of spider webs, orb-webs are the best investigated. Orb-weaving spiders generally use four different kinds of silk for the construction of their webs. 

The framework (frame and radii) of the web is built using the so-called dragline silk, originating from the major ampullate gland (MA gland). Before commencing the construction of the characteristic capture spiral, the spider uses minor ampullate spidroin (MIS) silk fibers (the proteins are produced in the minor ampullate gland, MI gland) to form a temporary auxiliary spiral. The role of the auxiliary spiral is to stabilize the emerging web structure and to serve as a template for the subsequently built capture spiral. It is important to mention that most female orb-weaving spiders can produce even more types of silk (glues and fibers) than the much smaller males, particularly to protect their offspring. Spider orb-web with dewdrops. At least four different types of silk are used to construct this complex structure.

The capture spiral itself is formed by flagelliform silk, and the involved protein is produced in the spider’s flagelliform gland. The interconnection of the different silks in an orb-web and the fixation of the web structure on a substrate is accomplished via a gluey, silk-like substance termed “attachment cement”, originating from the piriform gland. During evolution, each of the aforementioned silks was selected and optimized regarding their mechanical characteristics and functionalities, which in combination resulted in those fascinating, persistent, and mechanically stable structures of spider webs (Table 1). 

Table 1 Mechanical data of spider dragline silk compared to those of selected man-made high-performance fibers. The outstanding toughness, which is greater than that of the artificial fibers is the result of high strength combined with remarkable elasticity. If not otherwise mentioned, data was taken from references in the footnotes.
Material Toughness/MJ m−3 Strength/GPa Extensibility (%)Dragline silk (from Araneus diadematus) 160 1.1 27Kevlar 49TM (aromatic para-polyamide) 50 3.6 2.7Nylon 6,6 (polyamide) 80 0.95 18Carbon fiber 25 4 1.3
Assembly of spider silk fibersAmong the different types of spider silks, dragline silk is the most extensively studied and characterized. Thus, this silk is chosen to explain how the hierarchical organization of its proteinaceous components leads to a solid fibrous structure that mechanically outperforms man-made high-performance materials such as high-tensile steel and aramid fibers (such as Kevlar) when considering selected material characteristics (e.g. toughness and breaking strain) (Table 1). In general, dragline silk is a composite fiber whose main components are two types of spider silk proteins (spidroins). In the case of the golden orb weaver Nephila clavipes, these are the major ampullate spidroins (MAS), namely major ampullate spidroin 1 (MaSp1, with at least two genetic variations, each further comprising two or more allelic variants)21 and major ampullate spidroin 2 (MaSp2). Another intensely studied silk, the dragline silk of the garden cross spider Araneus diadematus, contains the A. diadematus fibroins 3 and 4 (ADF-3 and ADF-4). 

The assembly process of MAS leads to the formation of distinguishable substructures or structural patches, finally resulting in a hierarchically built proteinaceous fiber. Further coating of the core fiber with glycoproteins and lipids then yields the high-performance dragline silk used as the orb-web stabilizing scaffold and as the spider’s lifeline. The following sections will shed light on how the hierarchical structuring of two proteins can yield a complex proteinaceous thread with outstanding mechanical properties such as those of spider dragline silk.
The formation of dimers or oligomers via an intermolecular interaction of distinct α-helical secondary structure motifs seems to be a universal mechanism during silk fiber assembly since the non-repetitive domain of the spider egg case silk protein (TuSp1) also adopts a mainly α-helical conformation consisting of 5 helices, presenting surface exposed and contiguous hydrophobic patches acting as interaction domains for oligomerization.

Against the strategic background of sustainable development, exploration in the field of biomaterials has been continuously promoted. Compared with synthetic materials, researchers are paying increased attention to natural biomaterials.29,30 The continuous innovation and development of silk protein hydrogel materials, as the core carrier of biomimetic and regeneration, have greatly advanced the development process of biomedicine, created huge social and economic benefits, and opened up a new path for the development of global medical practices.  Silk protein hydrogels have a controllable molecular structure, excellent mechanical properties, and biological properties and are expected to become advanced model biomedical materials commonly used in the biomedical field. 

With the unremitting efforts of many scientific researchers, silk protein hydrogels and their composite hydrogel materials have been endowed with unique and excellent properties, such as injectability, high elasticity, high mechanical strength, and environmental sensitivity, and have achieved several satisfactory research results. The use of catechol with tissue adhesion properties to modify the hydrogel, giving the hydrogel high bioadhesion, can promote rapid wound healing.Benefits of Hyaluronic AcidHyaluronic acid is a compound that helps promote collagen production.

In a 2014 study, researchers treated wounds in mice with either water or hyaluronic acid. The wounds that received hyaluronic acid treatment improved more than those treated with water. Also, levels of two types of collagen were higher in the skin around those wounds.
Dermal fillers, which aim to reduce lines in the skin, often contain hyaluronic acid. The research found that a combination of hyaluronic acid and a purified polynucleotide helped boost the amount and quality of collagen in the skin and enhance skin elasticity. may also improve moisturization. The attributes of HA in combination with the features of silk, offer a useful suite of properties, combining the mechanical integrity and slow degradation of silk with the control of water interactions and biological signaling of HA.

Hierarchical structures made of proteins. The complex architecture of spider webs and their constituent silk proteinsMarkus Heim† , Lin Römer†‡ and Thomas Scheibel * Lehrstuhl für Biomaterialien, Fakultät für Angewandte Naturwissenschaften, Universität Bayreuth, Universitätsstr. https://pubs.rsc.org/en/content/articlehtml/2010/cs/b813273a

Challenges and opportunities of silk protein hydrogels in biomedical applications Junwei Liu, abc Xiaodong Ge, d Liang Liu, ac Wei Xu *bc and Rong Shao https://pubs.rsc.org/en/content/articlelanding/2022/ma/d1ma00960e

State of water, molecular structure, and cytotoxicity of silk hydrogels. Keiji Numata 1, Takuya Katashima, Takamasa Sakai https://pubmed.ncbi.nlm.nih.gov/21517113/

Hyaluronan enhances wound repair and increases collagen III in aged dermal wounds. Mamatha Damodarasamy, MS,1 Richard S. Johnson, PhD,2 Itay Bentov, MD, PhD,3 Michael J. MacCoss, PhD,2 Robert B. Vernon, PhD,4 and May J. Reed, MD1 Hyaluronan enhances wound repair and increases collagen III in aged dermal wounds - PMC (nih.gov)

Biomaterials from ultrasonication-induced silk fibroin-hyaluronic acid hydrogels. aXiao Hu 1, Qiang Lu, Lin Sun, Peggy Cebe, Xiaoqin Wang, Xiaohui Zhang, David L Kaplanhttps://pubmed.ncbi.nlm.nih.gov/20942397/