Lubrizol tested three classes of medical-grade polyurethane resins — Tecoflex®, Tecothane® and Carbothane® — for biocompatibility and biostability. Tecoflex® TPUs are a group of aliphatic polyether-based polyurethanes offered in eight standard grades. Tecothane® TPUs are a group of aromatic polyether-based polyurethanes offered in six standard grades. Carbothane® TPUs are a group of five standard grades of aliphatic polycarbonate-based polyurethanes.

The three classes of resins have been evaluated for biocompatibility and biostability using standard biological toxicity tests in addition to long-term implants. Biocompatibility tests were performed using procedures recommended by the Tripartite Commission for medical devices in contact with blood and tissue. Biostabilities of the resins were evaluated by physical property measurements and SEM (scanning electron microscopy) observations of the materials before and after implantation into living tissue.

The test materials were extruded into tapes and rods using processing conditions recommended by Lubrizol. The materials were ETO sterilized prior to testing. This was done in order to conform to common fabrication and sterilization procedures used for polyurethane medical device components.

The biocompatibility tests were performed by Toxicon Inc. (Bedford, MA). Complete test procedures and results are available upon request to Lubrizol, Inc.

BIOCOMPATIBILITY TESTING

MEM ELUTION TESTING: The biological reactivity of mammalian monolayers towards the test samples was determined. Minimum Essential Medium (MEM) extracts of extruded tape were layered onto L-929 mouse fibroblast cells grown on a solid support. No evidence of toxicity above the negative control material was observed for the Tecoflex®, Tecothane® or Carbothane® resins.

HEMOLYSIS TESTING: Samples of extruded tape were extracted in saline per USP guidelines. Whole rabbit blood was then added to the extracts and the percent of hemolysis was determined. All Tecoflex®, Tecothane® and Carbothane® materials were considered non-hemolytic.

USP CLASS VI TESTING: The USP Class VI testing includes three tests:
1) The Acute Systemic Test involves systemically injecting saline, ethanol, polyethylene glycol and cottonseed oil extracts of the test materials into mice. Injections of the Tecoflex®, Tecothane® and Carbothane® extruded tape extracts showed no evidence of toxicity.
2) The Acute Intracutaneous Test involves intracutaneously injecting saline, ethanol, polyethylene glycol and cottonseed oil extracts of the test materials into rabbits. Injections of the Tecoflex®, Tecothane® and Carbothane® extruded tape extracts showed no evidence of erythema, edema, eschar or clinical toxicity.
3) The Implant Test involves implanting a 1 mm x 1 cm rod of the test material into the paravertebral muscle of a rabbit for 7 days. No signs of hemorrhage, inflammation, necrosis, discoloration or encapsulation were associated with the Tecoflex®, Tecothane® or Carbothane® intramuscular implants compared to the USP negative control strips.

HISTOPATHOLOGY: Samples of all Tecothane® TPU grades, all Carbothane® TPU grades and Tecoflex® EG-60D were subcutaneously implanted into New Zealand rabbits for up to 90 days. Explanted samples were histologically evaluated by a pathologist. The test considered the following biological reaction categories: inflammation, encapsulation, hemorrhaging, necrosis and discoloration. Tecothane®, Carbothane® and Tecoflex® EG-60D materials meet the requirements for the Implantation Test under the Biological Tests for Plastics Section.

Rods of Tecoflex® EG-80A and EG-93A were subcutaneously implanted into New Zealand rabbits for 30 days. Explant samples were examined macroscopically considering the following biological reaction categories: inflammation, encapsulation, hemorrhaging, necrosis and discoloration. Tecoflex® EG-80A and EG-93A meet the requirements for the Implantation Test under the Biological Tests for Plastics Section.

MUTAGENICITY TESTING: A representative from each class of the polyurethanes was chosen and valuated for mutagenicity using the Ames Mutagenicity Assay. Tecoflex® EG-80A and EG-60D, Tecothane® TT-1055D and Carbothane® PC-3595A materials were selected to represent their respective class of materials. Extracts of the extruded Tecoflex®, Tecothane® and Carbothane® tapes were scored as non-mutagenic.

BIOSTABILITY TESTING

30-DAY AND 90-DAY SUBCUTANEOUS TESTING: All Tecothane® and Carbothane® implant samples were punched from 0.5 mm thick extruded tape using an ASTM D-1708 die. The approximately 1 cm x 3 cm samples were ETO or chemically sterilized prior to implantation. The samples, along with USP-polyethylene controls, were placed at the dorsal sites above the paravertebral muscle of mature New Zealand white rabbits. Each rabbit received 2 controls and 6 test implants (4 left side, 4 right side).

Tecothane® and Carbothane® TPU samples were explanted after 30 and 90 days. The explants were evaluated in terms of ultimate tensile strength, ultimate elongation and surface appearance. Tensile and elongation measurements of the explants were tested with control samples conditioned in the same manner but not implanted. The explant samples were examined by scanning electron microscopy to determine if the surface of the material showed signs of degradation.

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Tecoflex® TPU Results

BIOCOMPATIBILITY: Two basic types of medical-grade polyurethanes are manufactured under the Tecoflex® trademark. Both types of resins are made using the same diisocyanate (HMDI), the same chain extender (BDO) and the same additives (catalyst, antioxidant and lubricant). The difference is that the EG-80A and EG-85A resins use a PTMEG-2000 molecular weight polyol component while the EG-93A, EG- 100A, EG-60D, EG-65D, EG-68D and EG-72D use a PTMEG-1000 molecular weight polyol component.

Within a given resin type (PTMEG-1000 or PTMEG-2000) all reacting chemicals are the same. Only the ratios of the raw materials change in order to vary the hardness (durometer) of the urethane polymer. Therefore, there is no difference in biocompatibility between EG-80A and EG-85A. Nor is there a difference in biocompatibility among EG-93A, EG-100A, EG-60D, EG-65D, EG-68D and EG-72D. By the same token, blends of the resins within a given resin type have the same biocompatibility as the pure resin.

For these reasons, Lubrizol has performed extensive biological testing on one resin from each type. We chose EG-80A and EG-60D as representative resins. All other Tecoflex® resins fall within the same type as EG-80A or EG-60D. The biocompatibility test results for EG-80A and EG-60D are tabulated in Table 1.

The remaining durometers of resin have been checked for their biocompatibility in terms of cytotoxicity (MEM). The results of MEM Elution testing are found in Table 2. All the Tecoflex® resins passed the MEM Elution test.

The long-term biocompatibility of several Tecoflex® materials has been evaluated. Tecoflex® EG-60D passed a 90-day implant. Rod samples of EG-60D were implanted in the paravertebral muscles of rabbits for 7, 21 and 90 days. Microscopic examination of the 7, 21 and 90 day implanted samples were found to have no significant differences in pathologic findings when compared to a USP negative reference plastic.

Rods of Tecoflex® EG-80A, EG-93A and EG-60D were implanted for 30 days in paravertebral muscles of rabbits. These resins meet the requirements of USP XXII for Macroscopic Evaluation.

Biostability Testing

Testing Summary

PC-3555D
PASS