Hyperbranched poly(ethylene glycol)–trimesic acid polyesters as tunable scaffolds for modulating oxidative stress, calcium homeostasis, and neuro–keratinocyte interactions in tissue engineering

Abstract

The design of bioengineered scaffolds with tunable mechanical and biochemical properties is essential for advancing tissue regeneration strategies. In this study, we developed a series of hyperbranched poly(ethylene glycol)–trimesic acid (PEG : TMA) polyesters as customizable scaffolds for skin tissue engineering and peripheral nerve modulation. By systematically varying the PEG : TMA ratio (1 : 0.5 to 1 : 5), we achieved controlled branching and crosslinking, resulting in scaffolds with modifiable porosity and stiffness. The 1 : 2 PEG : TMA composition (S3) exhibited optimal characteristics—porosity (∼0.73 μm) and modulus (2–12 GPa)—to support efficient nutrient diffusion and robust cell adhesion, as evidenced by enhanced mitochondrial membrane potential (MMP) and regulated reactive oxygen species (ROS) levels. In contrast, the more densely crosslinked 1 : 5 formulation (S5) promoted keratinocyte alignment, neuronal adhesion, and neuro–epidermal interactions, while reducing oxidative stress and modulating basal cytosolic Ca²⁺ concentrations. Together, these findings highlight the potential of hyperbranched PEG : TMA scaffolds to finely tune cellular behavior and microenvironmental cues critical for tissue repair. The demonstrated biocompatibility, mechanical versatility, and bioactivity position this material platform as a promising candidate for regenerative medicine applications.