ABSTRACT Functional coatings based on amphiphilic polymer co‐networks (ACNs) offer a versatile alternative to hydrogel coatings with enhanced mechanical stability and tunable properties. This study explores ACN thin films composed of star‐shaped poly (ε‐caprolactone) (PCL) and poly (ethylene glycol) (PEG) with varying PEG content to optimize amphiphilic balance for cell adhesion. Low‐PEG films (9 and 15 wt. %) promote protein adsorption and cell attachment, whereas PEG‐rich films (38 and 47 wt. %) exhibit negligible protein adsorption and effectively inhibit cell adhesion. Crucially, an ultrathin decellularized and digested extracellular matrix (dECM) coating, physically anchored via hydrophobic interactions, provides cell‐recognition cues and restores cell adhesiveness on PEG‐rich ACN films. Film stiffness and roughness modulate cellular metabolic activity but do not affect initial cell adhesion, reaching attachment levels comparable to or exceeding those on tissue culture polystyrene. Drug‐proxy uptake depends strongly on network composition and swelling, with the highest uptake of Lucifer Yellow in PCL10PEG10 films (∼180 ng cm −2) and markedly higher uptake of Nile Red (∼10 µg cm −2). These results demonstrate that ACNs provide versatile biointerfaces with controlled molecular affinity, uptake capacity, and cell‐material interactions, while ultrathin dECM coatings offer a universal strategy to enhance bioactivity of PEG‐rich films.
El‐Faramawi et al. (Sun,) studied this question.