main issue with testing a biopolymer in an implant test is the absorption profile. Physical characteristics (such as form, absorption rate, metabolism characteristics, density, and surface hardness) can all influence the tissue response to the test material. Also, the choice of control articles should be matched as closely as reasonably possible to the test sample physical characteristics. This is recommended in order to allow comparison of the specific tissue reaction(s) with that of a similar material whose clinical acceptability and biocompatibility characteristics have been established to determine acceptance criteria for the test.
Another key consideration for the implant test for a biopolymer is with the implantation time points. ISO 10993‐6 states: “For absorbable materials, the test period shall be related to the estimated degradation time of the test product at a clinically relevant implantation site. When determining the time points for sample evaluation, an estimation of the degradation time shall be made.” Usually, in practice we try to estimate the absorption profile based on the specific metabolism rate and method of the material and the implant system. After this, we set three time periods: one where we first see degradation (usually between two and four weeks), second when half the sample is degraded, and third when we see a “steady state” in the sample material. A steady state is defined as a point in time where the body is no longer interacting with the material and no additional changes are happening. For example, in vivo implantation tests with a PLLA density scaffold demonstrated fast degradation in the first three weeks, after which the degradation rate progressively decreased [20]. This milestone is reached when the body has either encapsulated or otherwise dealt with the foreign material or when full degradation of the material has occurred.
As mentioned above, an appropriate control is the basis for the acceptance criteria of the test itself, making it an essential component for a relevant and applicable test system. The implantation test is set up so that the evaluation is conducted by comparing the result of the test site histopathology with the control site. Thus, if the chosen control article is a hard piece of metal or plastic that would not induce interaction with the surrounding tissues, then the comparison with the implant site of the biopolymer would probably not be favorable, leading to a higher tissue reactivity and making it look like the test material is non‐biocompatible. However, if an appropriate control is used, then the histopathological comparison of the test and control article sites can be made with confidence, and a correct understanding of the implantation risk of the material can be drawn.
1.5 Conclusion
Biopolymers occupy a unique and advantageous space as a medical device material. Devices made from these naturally occurring or biomimetic substances have the distinct advantage that the material itself is akin to those tissues the device contacts. From a bulk perspective, there is no concern regarding the material as a foreign body. Biopolymers also have environmental and manufacturing advantages as they are often produced not from petroleum derivatives but by living systems.
In contrast to the major advantages presented by biopolymers within the context of biocompatibility, there are a couple of key concerns that must be addressed. The natural origin of these materials does not mean that they are free from manufacturing residuals. Contact with solvents through manufacturing and purification steps can introduce contamination, as can contact with storage and primary packaging materials. Chemical analysis screening for these compounds can be complicated by the complex organic nature of the device material. Additionally, many biopolymers are degradable or resorbable by the body. While this is, in principle, a positive therapeutic effect, it can be difficult to prove that the safety of the device does not change over the degradation lifetime.
The pallet of materials afforded by biopolymers allows an even broader spectrum of medical devices with huge potential to help mankind. The biocompatibility principles discussed in this chapter can be applied to biopolymers to address concerns with regard to their safety. Use of thoughtful risk‐based testing strategies can conservatively mitigate risk, allowing more of these devices to reach full maturity in development and arrive on the market.
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