Histopathology of biodegradable polymers: challenges in interpretation and the use of a novel compact MRI for biocompatibility evaluation

Abstract

Toxicologic pathology is the art of assessment of potential adverse effects at the tissue level in pre‐clinical studies. In the case of biomaterials and medical devices, the toxicologic pathologists assess the safety (biocompatibility) and efficacy (conditions of the use) of the implantable materials. Proper assessment of biocompatibility of biomaterials is of utmost importance, since it helps to determine their safety after implantation in humans. Biomaterial‐related toxicity can be attributed to several factors, including for example leachable compounds from the material leading to thrombosis or carcinogenesis, or biodegradation of the material causing changes in its physical and compatibility properties. Evaluation of biocompatibility and biofunctionality involves assessment of cytotoxicity, allergic responses, irritation, inflammation and systemic and chronic toxicity. In many of these assessments, the toxicologic pathologist has an important role in determining product safety and potential toxicity. In this article, we review the special needs for proper toxicologic pathology assessment of biomaterials and degradable polymers. We review common adverse effects expected with biomaterials and describe their pathological picture and their clinical relevance. We also introduce a novel compact MR imaging technology as a tool for assessing biocompatibility and efficacy of implanted biodegradable materials, since it allows for the longitudinal imaging and quantification of inflammation in vivo caused by the device implantation, and enabling general inspection of shape, location and integrity of the device in vivo. Since the MR imaging technique is non‐invasive, the effects of the implantable device can be monitored longitudinally in the same animal without perturbation of the pathology. Copyright © 2014 John Wiley & Sons, Ltd.

Visualizing the In Vivo Evolution of an Injectable and Thermosensitive Hydrogel Using Tri‐Modal Bioimaging

“…Therefore, MRI is commonly used to evaluate the range of inflammation by the definite diagnosis of composition and the degree of edema. As illustrated in Figure 5a, no bright signal that reflected tissue edema or severe inflammation response [ 22 ] was detected around the two implanted hydrogels during the whole degradation period, indicating that the PLGA‐PEG‐PLGA hydrogel was biocompatible.…”

Long-term Local and Systemic Safety of Poly(l-lactide-co-epsilon-caprolactone) after Subcutaneous and Intra-articular Implantation in Rats

“…The mononuclear cell reaction is the expected body response to the presence of biodegradable material and indicative of progressive absorption of the test device material (PLCL; Nyska et al 2014).…”

“…They require both biodegradability and biocompatibility studies, with evaluation of these studies by toxicologic pathologists (Nyska et al 2014).…”

Castor oil–citric acid copolyester for tissue augmentation

“…Tissues were trimmed and sectioned at approximate 5‐µm thickness embedded in paraffin and stained with hematoxylin–eosin. The criteria for assessment of tolerability were based on grading the body response to the injected compound as follows: grade 1, slight reaction with a few inflammatory cells; grade 2, clear inflammatory reaction with one or two giant cells; grade 3, fibrous tissue with inflammatory cells, lymphocytes, and giant cells; and grade 4, granuloma with encapsulated implants and clear foreign‐body reaction …”