Evaluation of adipose-derived stromal cell infused modified-hyaluronic acid scaffolds for post cancer breast reconstruction

ABSTRACT Introduction Primary breast cancer surgery can compromise aesthetics and quality-of-life for breast cancer patients. While breast reconstruction improves these outcomes, current methods are limited by suboptimal aesthetic outcomes and potential complication risks. There is an urgent clinical need for improved approaches to post surgical reconstruction for breast cancer patients. Adipose-derived stromal cells (ADSCs) with biological scaffolds are being widely evaluated for tissue engineering applications in the field of reconstruction. Aims This study aimed to assess the biomechanical properties, biocompatibility, adipogenic potential of ADSCs encapsulated in modified hyaluronic acid derivatives in vitro; and efficacy and tissue integration of this construct in vivo in a murine breast cancer and reconstruction model. Methods ADSCs were obtained, with informed consent, from female breast cancer patients undergoing autologous breast reconstruction or cosmetic procedures (n=8) aged 47±12 years. Modified hyaluronic acid solution was combined with 1×10 6 ADSCs/mL and crosslinked using hydrogen peroxide and horseradish peroxidase. Young’s modulus, cell viability and adipogenic potential of the cell-loaded hydrogels were assessed in vitro. In vivo, hydrogels combined with murine ADSCs were grafted into a murine breast cancer model and tissues were harvested for immunohistochemistry after 4 weeks. Results ADSCs were characterised via morphology, Colony forming unit-fibroblast (CFU-F) assay, flow cytometry and multilineage differentiation. The cell-loaded hydrogels had a compressive Young’s modulus of 7.35±0.96 kPa after 21 days in culture, similar to human breast adipose tissue (∼10 kPa). High ADSC viability was observed after 21 days in culture, and ADSCs differentiated into mature adipocytes. After 4 weeks in vivo, hydrogels exhibited adipocytes, vascular endothelium, and pericyte-like cells. Conclusion This study demonstrates the potential suitability of modified hyaluronic acid hydrogels encapsulating ADSCs for adipose tissue engineering for post breast cancer reconstruction.