The Science of Artelon

Artelon

DEFINITION

Art•e•lon

  1. A polycaprolactone based polyurethane urea, built on well-known chemical components cleared for use in medical devices and specifically developed to be a biomaterial.

Many attempts to make biocompatible materials for orthopedic soft tissue reinforcement have failed. As a result, most surgeons stopped believing in the possibility of an optimal material.

Despite the hopelessness, some of the brightest minds in medicine, chemistry, biology and textiles set out on an expedition to create an optimal material.

This expedition led the creation of Artelon – the world’s first synthetic, biocompatible and degradable soft tissue reinforcement designed for orthopedic and podiatric surgery.

DEGRADATION

Quote – “Surgeons have been using degradable materials for centuries. Everything from pig gut to collagen patches, but they degrade too fast, and leave a host of new problems behind.”

– Per Flodin, Professor of Polymer Chemist.

Artelon was designed for surgeons wanting predictable degradation and reliable tensile strength.

Figure 1

Artelon Figure-1
Human biopsy from Augmentation Device ACL at 39 months illustrating signs of degradation of Artelon® (arrows) in varying stages. Light micrograph. Paraffi n section 3-5μm, toluidine blue stain. Bar=100μm.

Figure 2

Artelon Figure 2
Human biopsy from Augmentation Device ACL at 61 months showing residual inert microfragments of Artelon® (<100μm). Light micrograph. Paraffi n section 3-5μm, Htx-eosin. Bar=100μm.

Artelon degrades non-enzymatically [1,2] in the presence of water. A non-enzymatic degradation is predictable and not dependent on patient or implant site.

During degradation the original Artelon-polymer breaks down to shorter chains resulting in a resorbable and non-resorbable fraction. The resorbable fraction (6-hydroxycaproic acid) is eliminated from the body through the Krebs cycle (citric acid cycle)[1,2]. The non-resorbable fraction [low molecular weight poly (urethane urea) segments] is incorporated into the surrounding host tissue.

In vitro degradation tests show that fiber-based Artelon products retain about 90 percent of the tensile strength after one year, 80 percent of the tensile strength after two years, 50 percent after four years. The product has negligible mechanical integrity after six years [2].

BIOCOMPATIBILITY

Quote – “Many materials used to make implants for ligament reconstruction had failed, especially because they were not primarily developed for use in the human body”.

– Dr. Lars Peterson, Professor of Orthopedics and Artelon co-founder.

Figure 3

Artelon Figure 3
Artelon® (arrow) scaffold implantation in rat after three months. Image showing fi broblasts and almost mature connective tissue in close contact with the Artelon® material. No infl ammatory cells present. Light micrograph, Ladewig stain. Bar=100μm.

Figure 4

Artelon Figure 4
Rabbit tibia with Artelon® scaffold (arrows) at 3 months. Note the presence of mature, lamellar bone. Light micrograph, decalcifi ed paraffi n section, toluidine blue stain. Bar=50μm.

Figure 5

Artelon Figure 5
Rabbit tibia with Artelon® scaffold (arrows) at 6 months. Note the ingrowth of bone into the porous structure as well as the close contact between the Artelon® and bone. Light micrograph, decalcifi ed paraffi n section, toluidine blue stain. Bar=50μm.

Artelon has been through extensive testing to ensure patient safety. As part of the safety assessment of Artelon, comprehensive in vitro and in vivo safety tests have been performed by an independent, certified research laboratory according to the guidelines described in ISO 10993 – 1:2009 Biological Evaluation of Medical Devices. No signs of cytotoxicity, mutagenicity or contact hypersensitivity were detected in the tests [2,3]. The material is also non-toxic and non-allergenic [4,5].

To study the biocompatibility of Artelon, histological evaluations of inserted Artelon was implanted and surrounding tissues were performed at 6, 12, and 24 weeks, using a rabbit model [6]. At each time newly formed bone was observed within the porous structure of the Artelon implant, figure 3, 4 and 5. The macroscopic evaluation also did not find any signs of skin irritation or inflammatory reactions.

MECHANICAL PROPERTIES

Quote- “When Professor Dr. Lars Peterson asked if I knew of a biocompatible and degradable material for repairing torn ligaments, my reaction was – There’s no such thing”.

Per Flodin, Professor of polymer Technology

Figure 6

Artelon Figure 6
Human biopsy from ATR at 7 months. Tissue ingrowth is seen around and between the ATR fi bres. A close contact between the biomaterial and nicely organized connective tissue is seen. Light micrograph, Htx-eosin stain. Bar=50μm

Figure 7

Artelon Figure 7
Human biopsy from Augmentation Device ACL at 33 months. The blood vessels appear brown. Light micrograph, the section is stained with CD 34 antibody and DAB. Bar=20μm.

Figure 8

Artelon Figure 8
Human biopsy at 33 months from Augmentation Device ACL. Orientation of fi broblasts and collagen parallel to the Artelon. fi bers, in the direction of the tensional load. Light micrograph, toluidine blue stain..

Most alternative materials like collagen degrade quickly and have lost their mechanical properties in a few weeks. Due to the slow and predictable degradation of Artelon, the changes in its mechanical properties are well defined.

The unique textile design of Artelon implant makes it porous, facilitating vascularization and tissue ingrowth whether it is implanted in hard or soft tissue.

The results from comprehensive research on Artelon published Liljensten et al [7] demonstrated that the material was well tolerated by the host tissue and over time Artelon became closely integrated with connective tissue ingrowth and blood vessel formation between the fibers. (7, 8). These results have been confirmed by human biopsies taken at different times after implantation, figure 6. Mechanical loading has been shown to stimulate fibroblast proliferation and collagen synthesis along with collagen realignment, all of which promote repair and remodeling (Fig 8).

Mechanical loading has been shown to stimulate fibroblast proliferation and collagen synthesis along with collagen realignment, all of which promote repair and remodeling (Fig 8).

REFERENCES

[1] Woodruff MA, Hutmacher DW. The return of a forgotten polymer: Polycaprolactone in the 21st century.

Prog Polym Sci 2010;35(10):1217-56

[2] Gisselfält K, Edberg B, Flodin P. Synthesis and properties of degradable poly(urethane urea)s to be used for ligament reconstructions. Biomacromolecules.

2002 Sep-Oct;3(5):951-8.

[3] Irritation and delayed-type hypersensitivity test. (data on file)

[4] 3 month muscle implantation test in rabbit. (data on file)

[5] 6 month muscle implantation test in rabbit. (data on file)

[6] Bone implantation study in NZW rabbits. (data on file)

[7] Liljensten E, Gisselfält K, Edberg B, Bertilsson H, Flodin P, Nilsson A, Lindahl A, Peterson

  1. Studies of polyurethane urea bands for ACL reconstruction. J Mater Sci Mater Med. 2002 Apr;13(4):351-9

[8] Nilsson A, Liljensten E, Bergström C, Sollerman C. Results from a degradable TMC joint Spacer (Artelon®) compared with tendon arthroplasty. J Hand Surg Am. 2005 Mar;30(2):380-9.