Definitions
Degradation is defined as the decomposition of a material.
A degradation product is the product of a material which is generated by the chemical breakdown or decomposition of the material.
A Biomaterial is a material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body.
The test article shall be manufactured, processed, cleaned and sterilized as for the finished product. Should be handled in a manner to protect the integrity of the prepared finished product. Sample preparation should be as described in ISO 10993-12.
Non-Solid test articles may be put into tubes.
The site of implantation should be clinically relevant.
Absorbable material implants sites should be marked with an ink, dye or inert non-absorbable material such as a suture. The in vitro degradation should be considered first and a preliminary study done in rodents before testing in a larger animal.
Short term testing is commonly done in rodents or rabbits and long term testing is commonly done in rodents, rabbits, dogs, sheep, goats, and pigs.
Test and control should be in the same animal, but if evaluated as part of a toxicity study, test and control should not be in the same animal.
Inert materials are tested at a short timepoint of 1 to 4 weeks and long timepoints exceeding 12 weeks. A steady state of biological response should be the goal. Timepoints should go beyond absorption for degradable and absorbable test articles. Time points of bone implantations are longer than soft tissue.
At least three time points for absorbable materials. Before, during and after. This may require building additional animals and timepoints for materials with long absorption profiles.
It is recommended to get implant data from tox studies dosed by implantation.
A minimum of 3 animals are required.
Degradation is defined as the decomposition of a material.
A degradation product is the product of a material which is generated by the chemical breakdown or decomposition of the material.
A Biomaterial is a material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body.
The test article shall be manufactured, processed, cleaned and sterilized as for the finished product. Should be handled in a manner to protect the integrity of the prepared finished product. Sample preparation should be as described in ISO 10993-12.
Non-Solid test articles may be put into tubes.
The site of implantation should be clinically relevant.
Absorbable material implants sites should be marked with an ink, dye or inert non-absorbable material such as a suture. The in vitro degradation should be considered first and a preliminary study done in rodents before testing in a larger animal.
Short term testing is commonly done in rodents or rabbits and long term testing is commonly done in rodents, rabbits, dogs, sheep, goats, and pigs.
Test and control should be in the same animal, but if evaluated as part of a toxicity study, test and control should not be in the same animal.
Inert materials are tested at a short timepoint of 1 to 4 weeks and long timepoints exceeding 12 weeks. A steady state of biological response should be the goal. Timepoints should go beyond absorption for degradable and absorbable test articles. Time points of bone implantations are longer than soft tissue.
At least three time points for absorbable materials. Before, during and after. This may require building additional animals and timepoints for materials with long absorption profiles.
It is recommended to get implant data from tox studies dosed by implantation.
A minimum of 3 animals are required.
Macroscopic evaluation of regional lymph nodes should be conducted. The sites should be evaluated macroscopically for hematoma, edema, encapsulation and any other abnormal findings. This can occur after tissue fixation.
Microscopic evaluation should assess inflammation, neovascularization, fibrosis, fatty infiltrate, necrosis and foreign debris on a scale of 0 to 4 running from none to extensive or severe. The scores for each site is tallied, eventually all the numbers are crunched to have an overall mean score for all sites for all animals for both test and controls. The control score is subtracted from the test for the overall score. The test article is then classified as a non, slight, moderate or severe irritant based upon the scores which can range from 0 to over 15.
Subcutaneous implantation:
Sizes for various types of test articles are suggested. The common measurement is a thickness of of approximately 1.5 mm, but in one instance up to 4 mm.
In the subcutaneous space of rats, mice, guinea pigs, or rabbits
A minimum of 3 animals and a minimum of 10 sites of each material.
Anatomical sites suggested of along the dorsal midline, or in the neck.
Intramuscular Implantation:
The implant should be 1 to 3 mm in diameter and 10 mm long with rounded ends.
The paravertebral muscles of rabbits are the preferred site.
A minimum of 3 animals to yield a minimum of 10 test and 10 control sites.
Implantation using a hypodermic needle is specified although alternative methods can be used when appropriate for the test article. Larger implants can be put in surgically.
Implantation into bone:
The implant can be screw shaped to add stability to the implant. Also a cylinder is acceptable. And will be 2 mm in diameter and 6 mm in length if cylinders used in rabbits, 4 mm in diameter and 12 mm in length cylinders used in dogs, sheep, or goats, and 2 to 4.5 mm in diameter if screw shaped in rabbits, dogs, sheep, goats or pigs.
Test and control have to be in contralateral locations.
The femur or tibia are discussed as the implant sites.
The maximum sites for a rabbit are 3 test and 3 control. The maximum sites for a dog, sheep, goat or a pig is 6 test and 6 control.
Microscopic evaluation should assess inflammation, neovascularization, fibrosis, fatty infiltrate, necrosis and foreign debris on a scale of 0 to 4 running from none to extensive or severe. The scores for each site is tallied, eventually all the numbers are crunched to have an overall mean score for all sites for all animals for both test and controls. The control score is subtracted from the test for the overall score. The test article is then classified as a non, slight, moderate or severe irritant based upon the scores which can range from 0 to over 15.
Subcutaneous implantation:
Sizes for various types of test articles are suggested. The common measurement is a thickness of of approximately 1.5 mm, but in one instance up to 4 mm.
In the subcutaneous space of rats, mice, guinea pigs, or rabbits
A minimum of 3 animals and a minimum of 10 sites of each material.
Anatomical sites suggested of along the dorsal midline, or in the neck.
Intramuscular Implantation:
The implant should be 1 to 3 mm in diameter and 10 mm long with rounded ends.
The paravertebral muscles of rabbits are the preferred site.
A minimum of 3 animals to yield a minimum of 10 test and 10 control sites.
Implantation using a hypodermic needle is specified although alternative methods can be used when appropriate for the test article. Larger implants can be put in surgically.
Implantation into bone:
The implant can be screw shaped to add stability to the implant. Also a cylinder is acceptable. And will be 2 mm in diameter and 6 mm in length if cylinders used in rabbits, 4 mm in diameter and 12 mm in length cylinders used in dogs, sheep, or goats, and 2 to 4.5 mm in diameter if screw shaped in rabbits, dogs, sheep, goats or pigs.
Test and control have to be in contralateral locations.
The femur or tibia are discussed as the implant sites.
The maximum sites for a rabbit are 3 test and 3 control. The maximum sites for a dog, sheep, goat or a pig is 6 test and 6 control.
