Investigating the inflammatory responses to organic biomaterials in models of Parkinson’s disease: a systematic review

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, resulting in chronic death of dopaminergic neurons in the midbrain. Although the cause is unclear, there is a strong relationship between neuroinflammation and neurodegeneration. This has led to the development of a wide variety of experimental therapies that specifically deliver cells, drugs, genes, and anti-inflammatory molecules to target diseases. Although biomaterials are promising carriers or scaffolds that can protect therapeutics from degradation and improve their efficacy, they can also cause inflammation. This affects not only the pre-clinical development of drugs but also clinical treatment. However, biomaterial-induced inflammation has not been systematically assessed. This systematic review synthesizes data on such responses from in vitro and in vivo studies on organic biomaterials designed for therapeutic delivery in PD. Following the PRISMA 2020 guidelines, a database search was conducted in PubMed and Web of Science for papers published before January 2025. Sixty studies published over the last 20 years were selected. The PD models and inflammatory biomarkers assessed indicate that there is a large variation in the models and experimental endpoints in investigating such biomaterials. This review highlights that most biomaterials do not provoke neuroinflammation, and many elicit anti-inflammatory effects.