Chitosan for anti-ageing
Dr Alexandre Guerry explains a new anti-ageing approach from BIOXIS, which is based on using natural and biodegradable chitosan polymers
BIOXIS Pharmaceuticals have used their expertise in regenerative medical devices and research and development of chitosan medical devices for the aesthetic field, to create the Monophasic Tissular Inductor—the first injectable medical device based on chitosan.
This industry first Monophasic Tissular Inductor is based on an injectable chitosan matrix: MTI-12. Uniquely formulated with a chitosan matrix for regenerating collagen while repairing soft-tissue, this technology aims to change the way doctors are repairing soft tissue ageing.
Liquid-to-gel delivery mechanism
MTI-12 technology is formulated from a chitosan derivative, which is a liquid solution until it enters the skin. In solution, chains of chitosan are flexible and mobile. After injection, the physiological media trigger to the chains’ organisation into a chitosan network and after several minutes the solution turns into gel due to pH change. Unlike chitosan solution, chitosan matrix exhibits mechanical properties such as elasticity and a strong non covalent hydrogen bond, in which no crosslinked toxic agent is needed. This allows more flexibility in term of shaping and modelling before complete gelification.
Thinner needles can be used, making injection easy and painless, and precision high. Post-injection, the doctor has three to five minutes—before the filler becomes a gel—in which to sculpt and adapt the dermal filler at the area of injection for a perfect result.
Controlled collagen stimulation
MTI-12 technology induces a controlled generation of neo-tissues. Over time, the chitosan implant degrades naturally and is replaced by more complex neo conjunctive tissue, including vascular tissue. The degradation is due to natural hydrolysis, mechanical stress, scavenger properties, and slow degradation by a non specific enzyme.
MTI-12 regeneration process
The technology induced tissues are naturally textured and uniformly sustained, without loss of volume between the resorption of the implant and the creation of the neo-tissues (Estimation based on in vivo pig model).
Examination of histology images shows how injection of MTI-12 technology triggers a controlled regeneration of tissues such as collagen and vascular tissue, at the interface between the implant and the host tissues. The neo-tissues stimulation is based on the presence of inflammatory cells. The interaction between chitosan and macrophage establishes a favourable environment for the formation of collagen and the resorption kinetic of chitosan allows the maturation of tissues. The generated tissue is more closed than classic scar tissues. With time, the chitosan implant is progressively replaced by matured tissues.
Seven days after injection, the regenerative response is largely initiated and the first collagen fibres are synthesised by fibroblasts around the implant and start to invade it.
After 12 weeks, the implant is still intact in large areas, but has been degraded at the surface by anti-inflammatory macrophage. The chitosan implant is separated from the cutaneous muscle by a thin collagen band. Alongside the formation of these neo conjunctive tissues, neovascularisation is at work—new functional vessels were founded in vivo studies.
From this pig model study we can conclude that since the chitosan hydrogel has mostly disappeared by 12 weeks, the observed volume effect is mostly the result of neo-tissue synthesis.
Evidence exists that shows that during its degradation process, the fragments are phagocytised by macrophage and/or polynuclear cells, implying a chitosan bioresorption at cellular level.
Long lasting effect
BIOXIS Pharmaceuticals has undertaken comparative studies, which demonstrate a clear advantage over leading “volume-effect” products in terms of neo-tissue induced. In rats, MTI-12 monophasic technology was found to have stimulated 25% more collagen growth than its nearest rival. This collagen is also closer to natural collagen than that induced by PPF fillers, or during skin reconstruction after a skin accident such as burns.
Currently, BIOXIS owns three patents on its chitosan technology and is undertaking the CE marking of its MTI-12 dermal filler product with commercial launch planned for 2017. After the CE mark is granted in 2017, some longer term human clinical studies will be undertaken to determine more precisely the long-lasting effects of the ‘biological’ filling of MTI-12 injectable implant. Based on the superiority of MTI-12 technology observed in the comparative study with PPF’s and HA fillers, this time may be estimated to be between 14 and 18 months (Estimation based on in vivo studies).
MTI-12 technology is the first particle-free monophasic tissular inductor.
The absence of particles is an important benefit for doctors and patients as it could significantly lower the number of adverse side effects, such as granulomas and nodules that can develop under the skin. Moreover the polysaccharide nature of chitosan allows its complete degradation and natural metabolisation.
The security of MTI-12 has been tested in five in vivo studies. In addition, an in vitro cytotoxicity test conducted according to the ISO 10 993-5:2009 directive demonstrated that chitosan is biocompatible and does not induce specific toxicity in direct contact. This technology also has all naturally occurring advantages of chitosan including a biodegraded and bio-resorbed matrix, antibacterial and hypoallergenic characteristics.
MTI-12 technology is based on BIOXIS Pharmaceuticals expertise in chitosan, a natural polysaccharide derived from chitin, found in fungus, insects and shellfish. Chitosan is composed by long chain of glucosamine: a natural residue already found in human body. Contrary to over formulation based on polysaccharide (hyaluronic acid, CMC…), the human body does not produce specific degradation enzymes against chitosan. This characteristic permits to chitosan to be formulated without toxic crosslinked agents. Chitosan is already used in agricultural, industrial, cosmetic and medical device industries. Because it is biocompatible, biodegradable, non-toxic and antimicrobial, it is an attractive biomaterial for tissue engineering. In the health sector, several chitosan-based tissue regenerating scaffold devices are already available in the market for cartilage regeneration or hemostatic dressing.
Bioxis are a Lyon based company who work in cooperation with the French National Center of Scientific Research (CNRS), the Lyon 1 University and the National Institute of Applied Science (INSA). The company have been supported by major organisations of the French biotech ecosystem, such as BPI France, Medicen (healthcare cluster of the Paris region), Ministry of Foreign affairs (COOPOL), LyonBiopole (healthcare cluster of the Lyon) & I-Care (healthcare technology cluster of Rhône-Alpes region).