Artificial Joint Fluid

Articular cartilage is a tissue that exhibits ultra-low friction and little wear over several decades. However, its limited self-renewing abilities can become a serious issue once the cartilage layer is damaged by trauma or disease. Damaged cartilage gives rise to ongoing irritations and inflammations that limit patient mobility and cause severe pain. Indeed, osteoarthritis is a frequent problem not only among the elderly population. To date, the most common, non-invasive treatment of osteoarthritis is the injection of hyaluronic acid (HA). HA is a natural component of the synovial fluid and increases its viscosity - thus improving the stability of the lubrication film. Furthermore, HA is thought to interact with other surface bound glycoproteins to further reduce friction. However, if the cartilage surface – and also the surface bound macromolecules – are damaged, the lubricating potential of HA is limited. Although they are physiologically not present in the synovial fluid, mucins can adsorb to the cartilage surface where they form a hydrated, protective layer. We could already show, that mucin solutions can outperform HA solutions in terms of wear protection in articular cartilage tribology. Thus, solutions of purified mucins could be a powerful alternative to current osteoarthritis treatment strategies.

Literature:

Boettcher et al., Quantification of cartilage wear morphologies in unidirectional sliding experiments: Influence of different macromolecular lubricants, Biotribology (2017)

Kienle et al., Comparison of friction and wear of articular cartilage on different length scales, Journal of Biomechanics  (2015)

Baena et al., 3D quantitative characterization of degraded surfaces of human knee cartilages affected by osteoarthritis, Wear (2014)

Contact Lens

With a prevalence of more than 10 %, keratoconjunctivitis sicca (commonly known as dry eye syndrome) is one of the most frequent forms of ocular diseases; among contact lens wearers, this condition occurs even more often. Mucins are a key component of the ocular tear film and also here serve as a molecular lubricant. In the absence of a proper mucinous lubrication layer on the cornea surface, increased friction and tissue damage induced by contact lens sliding leads to discomfort. We have recently shown that purified gastric mucins efficiently prevent damage on the cornea. This protective effect can be achieved in two different ways: mucin solutions can be used as ‘artificial tears’ (eye drops) for cornea lubrication or as a molecular coating on contact lenses. One option to achieve such a mucin coating on contact lenses could be to add the purified molecules to contact lens storage solutions thus increasing the wearing comfort of both simple and state-of-the-art contact lenses.

Literature:

Winkeljann et al., Mucin Coatings Prevent Tissue Damage at the Cornea–Contact Lens Interface, Advanced Materials Interfaces (2017)

Hofmann et al., In-vitro method for determining corneal tissue friction and damage due to contact lens sliding, Biotribology (2016)

Medical Devices

As a part of surgery or post-surgery measures, catheters, ventilation tubes or stents are inserted into the human body. Those tubes are typically made from polymers and cause friction on the tissue epithelia they rub across, which causes discomfort and may damage the tissue. Moreover, if those artificial objects remain in the body for extended time periods (several days up to weeks), another issue starts to play a role: biofouling, i.e., the uncontrolled deposition of proteins or other biomolecules onto the surface of the tubes which is typically followed by colonization of bacteria. This process negatively impacts the proper function of the tubes and can also lead to inflammation. Under lab conditions, mucin-coatings of synthetic materials such as polystyrene and glass were already generated by passive adsorption and could successfully reduce biofouling events. Generating stable, covalent mucin coatings on medical devices such as catheters or ventilation tubes could greatly improve their biocompatibility.

Literature:

Co et al., Probing the Role of Mucin‐Bound Glycans in Bacterial Repulsion by Mucin Coatings, Advanced Materials Interfaces  (2015)

Janeiro et al., Mucin Covalently Bonded to Microfibers Improves the Patency of Vascular Grafts, Tissue Engineering Part A (2014)
 
Sandberg et al., Potential use of mucins as biomaterial coatings. I. Fractionation, characterization, and model adsorption of bovine, porcine, and human mucins, Journal of Biomedical Materials Research Part A (2008)

Wound Gels

Bacterial and viral infections still represent a major cause of diseases that may lead to severe illness or even death. In healthy adults, the intact skin provides a first barrier against such microbial infections. However, in situations where this natural barrier is compromised, e.g. trauma, injuries, or surgery, the risk of contracting an infectious disease is drastically increased. In contrast to the outer skin, all wet epithelia are covered with mucus, where the mucus serves as an initial barrier against microbial attack. Indeed, mucins combine anti-bacterial and anti-viral properties. Thus, mucin based wound gels could be a promising tool to overcome the temporal inability of the damaged skin to protect the underlying tissue from infections. By adding other biopolymers, e.g. methylcellulose, or by covalently cross-linking the mucin glycoproteins, the mechanical properties of the mucin gels can be adjusted to form a stable cover. Such mucin-based hydrogels can be enriched with drugs or drug carrier particles that release pharmaceuticals in a time controlled manner. Such tailored drug delivery systems can be an important tool to further improved the healing process of damaged tissues.

Literature:

Nowald et al., A Selective Mucin/Methylcellulose Hybrid Gel with Tailored Mechanical Properties, Macromolecular Bioscience  (2016)

Duffy et al., Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery, Acta Biomaterialia  (2015)

Lieleg et al., Mucin biopolymers as broad-spectrum antiviral agents, Biomacromolecules  (2012)

ELISA Lab Test

For the biochemical analysis of biological mucus samples, e.g., as part of a clinical evaluation of mucus specimens from patients with cystic fibrosis, different lab tests are available. One of the most frequent lab tests used to identify certain biomolecules is ELISA (Enzyme-linked Immunosorbent Assay), which makes use of a set of two antibodies to detect target molecules and to visualize them with a chromophore reaction. However, to give quantitative results, this well-established assay requires purified solutions of the target molecule as a standard. Currently, the compromised structure of industrially purified gastric mucins prevents their detection by antibodies – although the very same antibodies do detect those gastric mucins if they are manually purified in the lab. Thus, a better availability of highly functional purified mucins will simplify the analysis of clinical mucus samples and thus could contribute to a better detection of mucus-related diseases and their treatment.

Mouth Spray

Especially among the elderly population, but also as a side-effect of chemotherapy treatment, many people suffer from a dry mouthfeel (xerostomia). Xerostomia not only leads to a permanent feeling of oral discomfort but also makes the ingestion of food difficult: without a proper oral lubricant, chewing and swallowing becomes complicated and very unpleasant. The missing lubricity in the oral cavity of dry mouth patients is mostly due to a reduced or altered production of salivary mucins. Thus, using mucin containing aqueous solutions for the treatment of xerostomia symptoms might seem obvious. However, although commercially available products comprising industrially purified mucins exist, these mucins have lost many of their native properties – probably as a consequence of harsh chemical conditions during the purification process. In fact, only a few labs worldwide are able to purify highly functional mucins, and often only in small quantities.

Literature:

Winkeljann et al., Oscillatory Tribology Performed with a Commercial Shear Rheometer, Biotribology (2018)

Biegler et al., Cationic astringents alter the tribological and rheological properties of human saliva and salivary mucin solutions, Biotribology (2016)

Kocevar-Nared et al., Comparative rheological investigation of crude gastric mucin and natural gastric mucus, Biomaterials (1997)