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15 listopada 2017

Development story

“Flexibility, Porosity Design Leads to Regeneration of Soft Tissue” by Dr. Torbjörn Mathisen published in Medical Design Technology, September 2014

From idea to clinical reality of a new type of biosynthetic surgical mesh

The design of surgical biosynthetic mesh for breast surgery, whether reconstructive or cosmetic, and for hernia or abdominal surgery involves creating material and design that promotes faster healing with natural human tissue regeneration. It’s been an exciting journey for me and my colleagues to develop our patented TIGR Matrix surgical mesh using new polymers, a new knitting process and now having four years of preclinical and clinical data to back — our original premise.

The Rationale

Surgical mesh was and is still made by polypropylene — it is not a very good and biocompatible material. I took the idea to one doctor who was very supportive of using degradable polymer material. It simply works better for healing because the human body is an amazing self-healer. It just needs some help!

That was in April 2004 — the beginning of the TIGR development project.

It’s been ten years since the idea was born. We used the rest of 2004 to convince our current owner that this could be a great project, meet with general surgeons and complete the first patent application. The actual development work actively began in 2005.

So we sought a mesh that could promote the regeneration of functional connective tissue in a more predictable way than the polypropylene already in use. Such a feature would require an active remodeling of the first deposited scar tissue and, hopefully, also allow for a more unique positioning of the product in the market

If you think about it — if we place a mesh in the body, the inflammatory reaction that follows will create scar tissue, which is normal. But we wanted the scar tissue to be remodeled over time into functional collagen, something most polypropylene mesh can’t accomplish, since the cells in the vicinity of the mesh is unable to sense the load situation which is taken up by the mesh .

To review the normal wound healing process, the first one to two weeks are critical and we figured that TIGR should be rather rigid and not allow too much movement during this period, but slightly stimulate collagen deposition. During these first days after implantation, the mesh should be firmly anchored at the implant site by firm integration of new, but yet immature, tissue. Only then, the mesh would be part of stabilization of the wound and minimizing risks for wound rupture.

The next stage should open up for a gradual increase in the mesh stretch-ability (or elongation) to allow the cells to feel the load situation. It was our hypothesis that if the newly regenerated tissue, very early in the process could feel the load situation it would more easily remodel into functional connective tissue.

Cells attaching to a mesh with the properties described above will have a different signaling pattern compared to cells resting on a polypropylene surface having the same mechanical properties during the full remodeling cycle. To accomplish what I refer to as dynamic remodeling, the mesh should be well integrated and increasingly stretchy over time in order for the cells to respond to and take over the load situation. The remodeling process will then result in a more functional connective tissue. The above was my philosophy in setting the parameters for the TIGR specs.

The most important thing is to keep mesh stable for the first week, then gradually allow the mesh to start to remodel the wound permitting new collagen that is aligned in the load situation.

We did a three year animal study in sheep and we were able to demonstrate this. There is much more research involved today and we have years of data in actual human application following our FDA approval.

This could be one step in the right direction for good regeneration of a soft tissue defect such as a hernia. We have to make a mesh that actually allows mechanical changes over time that facilitates the body to naturally and efficiently take over the load.

The Materials

To accomplish the rather demanding specification on the mesh we had to design TIGR with at least two degradable fibers having different degradation times –which is the basis of our patent. One fiber have a relative short degradation time and is the key for the keeping stability and not allow too much elongation during the first week after implantation. This one is very similar to the suture known as Vicryl that came out way back in the 1970s.

For the second fiber, we knew we needed more strength for at least three months after the first fiber was gone. That required another specification. The mesh must remain strong but allow for greater mobility and therefore we chose a slower degrading material and settled with a fiber from the lactide polymer family blended with trimethylene carbonate to increase the elasticity of the fiber.

Lactide and glycol polymers have been in clinical use again since the early 1970s. They are simply polyesters degrading with the help of water into simple metabolites already present in our body. The first stage in the degradation process is the decline in mechanical properties followed by a weight loss. The degradation products are absorbed by local tissue and metabolized into carbon dioxide and water via Krebs cycle.

The Manufacturing Process

Except for making of the material, polymerization, and the fiber spinning process-manufacturing is actually very aligned with the textile industry and rather straightforward.

After the fiber has been spun and transferred to suitable vehicles for the knitting machine the mesh is knitted using a special warp knitting technique. Finally the mesh is cut to proper surgical sizes and placed in moisture proof packages and sterilized.

Using the warp knitting technique was necessary to achieve the specific characteristics found in TIGR which we think are so important for remodeling of the wound. It also creates well defined porosity in TIGR which is so important for tissue regrowth and anchorage of the product. Furthermore, it provides the surgeon with a mesh which can be adjusted by a pair of scissors without the risk of unraveling or poorer retention of sutures.

One of the challenges during the development project was to combine two so different fibers in the knitting machine and to achieve the final properties we wanted. Generally the type of materials used in TIGR is very sensitive towards heat and moisture and this provide us with everyday challenges in our production. That is also the reason for why the product is packed in aluminum pouches to protect it from moist air. Even though most of the equipment is ordinary, the materials requires some special attention during production. Polypropylene, commonly found in surgical meshes, is on the other hand a very forgiving material and usually very easy to process.

The Future

Knitted structures will have an interesting future when it comes to this application and also within tissue engineering. It seems like the cells like this type of knitted structure. The cells attaches very nicely in and around the individual fibers. This is a prerequisite for these cells to proliferate and create even more collagen. There is so much more collagen formed around TIGR than what you get with a polypropylene mesh and we have the first tests showing that we gradually is building Type I collagen over time, an indication that the remodeling process is favorable and that functional and strong collagen is formed..

The human body is fantastic in healing itself if you provide supporting structures for the tissue to grow. That was my first job — to convince the doctors that meshes for soft tissue repair could be made from degradable materials to avoid negative chronic effects. They thought mesh had to be permanent.

Doctors today talk about resorbable polymers very naturally. They see inert meshes may cause problems in patients so today doctors understand the benefit in degradable materials much better than back in 2004 when we first started.

Read the article as seen in Medical Design Technology here:

Read more about TIGR® Matrix Surgical mesh.