Investigating the Effect of Tissue Engineering Scaffold Architecture on Cell Morphogenesis

Fibrin-based scaffolds are a promising tissue engineering device, particularly for applications in skin regeneration, due to their bio-inductive properties. This study, conducted in collaboration with Oxartis Ltd., focussed on the design optimisation and characterisation of Oxartis’ flagship scaffold technology, applied to developing fibrin based scaffold for clinical applications in wound healing and regenerative medicine. The study investigated the impact of the architecture, chemical composition, cellular interactions of fibrin scaffolds, aiming to optimise their design for tissue engineering applications. The ProMatrix BioDerm scaffolds were fabricated using oil in water emulsion-templating technique, employing decane as the oil phase while fibrinogen and thrombin formed the aqueous phase, and an experimental range of surfactant concentrations supported the the interphase. Crosslinking with glutaric dialdehyde and reduction using sodium borohydride steps were employed to form and stabilise Schiff base adducts and neutralise residual dialdehydes, respectively. Comprehensive characterisation included scanning electron microscopy (SEM) for pore morphology, Fourier-transform infrared (FTIR) and nano-FTIR spectroscopy for compositional analysis, and biomechanical testing using probe dynamic mechanical analysis (ProbeDMA) and atomic force microscopy (AFM). Cellular assays, including live-dead staining and proliferation studies, evaluated the scaffolds' ability to support cell morphogenesis. The findings revealed that surfactant concentration significantly affects scaffold architecture, with lower concentrations producing larger, irregular pores and higher concentrations yielding smaller, more uniform structures. Quantitative pore area analysis demonstrated median values ranging from ∼400 µm² at 0.2% surfactant concentration to ∼800 µm² at 0.05%. Cellular assays confirmed optimal cell adhesion, migration, and cytoskeletal engagement on scaffolds fabricated with moderate surfactant concentrations (0.05% and 0.025%), suggesting a balance between porosity and fibre connectivity. This study highlights the clinical potential of the ProMatrix BioDerm scaffold and underscores the importance of optimising scaffold design parameters for tissue integration and regenerative applications. Future work will benchmark these scaffolds against commercial products such as Matriderm® and Integra® to support their clinical translation and application in advanced wound care solutions.