In vivo biocompatibility testing of nanoparticle-functionalized alginate-chitosan scaffolds for tissue engineering applications

Nancy G Viveros-Moreno; Mario Garcia-Lorenzana; Eduardo Peña-Mercado; Josune García-Sanmartín; Judit Narro-Íñiguez; Marcela Salazar-García; Sara Huerta-Yepez; Concepción Sanchez-Gomez; Alfredo Martínez; Nohra E Beltran-Vargas

doi:10.3389/fbioe.2023.1295626

In vivo biocompatibility testing of nanoparticle-functionalized alginate-chitosan scaffolds for tissue engineering applications

Front Bioeng Biotechnol. 2023 Nov 23:11:1295626. doi: 10.3389/fbioe.2023.1295626. eCollection 2023.

Affiliations

¹ Doctorado en Ciencias Biológicas y de la Salud, Universidad Autonoma Metropolitana, Ciudad de Mexico, Mexico.
² Department of Reproduction Biology, Division of Biological and Health Sciences, Universidad Autonoma Metropolitana, Iztapalapa, Mexico.
³ Department of Processes and Technology, Division of Natural Sciences and Engineering, Universidad Autonoma Metropolitana, Cuajimalpa, Mexico.
⁴ Angiogenesis Group, Center for Biomedical Research of La Rioja (CIBIR), Logroño, Spain.
⁵ Research Laboratory of Developmental Biology and Experimental Teratogenesis, Children's Hospital of Mexico Federico Gomez, Mexico City, Mexico.
⁶ Research Laboratory of Hematooncology, Children's Hospital of Mexico Federico Gomez, Mexico City, Mexico.

Abstract

Background: There is a strong interest in designing new scaffolds for their potential application in tissue engineering and regenerative medicine. The incorporation of functionalization molecules can lead to the enhancement of scaffold properties, resulting in variations in scaffold compatibility. Therefore, the efficacy of the therapy could be compromised by the foreign body reaction triggered after implantation. Methods: In this study, the biocompatibilities of three scaffolds made from an alginate-chitosan combination and functionalized with gold nanoparticles (AuNp) and alginate-coated gold nanoparticles (AuNp + Alg) were evaluated in a subcutaneous implantation model in Wistar rats. Scaffolds and surrounding tissue were collected at 4-, 7- and 25-day postimplantation and processed for histological analysis and quantification of the expression of genes involved in angiogenesis, macrophage profile, and proinflammatory (IL-1β and TNFα) and anti-inflammatory (IL-4 and IL-10) cytokines. Results: Histological analysis showed a characteristic foreign body response that resolved 25 days postimplantation. The intensity of the reaction assessed through capsule thickness was similar among groups. Functionalizing the device with AuNp and AuNp + Alg decreased the expression of markers associated with cell death by apoptosis and polymorphonuclear leukocyte recruitment, suggesting increased compatibility with the host tissue. Similarly, the formation of many foreign body giant cells was prevented. Finally, an increased detection of alpha smooth muscle actin was observed, showing the angiogenic properties of the elaborated scaffolds. Conclusion: Our results show that the proposed scaffolds have improved biocompatibility and exhibit promising potential as biomaterials for elaborating tissue engineering constructs.

Keywords: alginate; biocompatibility; chitosan; foreign body reaction; subcutaneous implantation.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. Children’s Hospital of Mexico Federico Gomez (protocols HIM/2020/059 and HIM/2022/040).