Polydopamine-assisted ion-mediated hyaluronic acid grafting for effective construction of hemocompatible platform with cancer cell recognition.

Surfaces capable of specific biomolecule recognition are essential for cancer theranostics, biosensing, and tissue engineering. However, current grafting methods, critical for dictating the recognition efficiency and biocompatibility of biomaterials, especially hydrophilic polymers, struggle to balance high grafting density with ease of implementation. In pursuit of a simple, effective, and versatile solution, we introduced a polydopamine (PDA)-assisted Ca-mediated grafting strategy using hyaluronic acid (HA) as a model material. By increasing the PDA amine group density through deposition time optimization and coiling HA conformation via Ca-mediation, the grafting density of aldehyde-bearing HA enhanced 13 folds and reached 2.4 ± 0.2 × 10 chains μm. After removement of Ca ions, the dense HA grafting was highly stretched on PDA-coated substrates, close to the contour length of HA. Ca-mediated HA (CamHA) grafting was then implemented on versatile substrates with PDA assistance, demonstrating enhanced hemocompatibility by reducing protein adsorption and blood cell interference. Furthermore, the dense and stretched HA chains in CamHA enhanced interactions with CD44, enabling selective recognition of CD44-high cells under static and dynamic conditions. The PDA-assisted CamHA grafting presents a model system for studying the effects of regulated biomaterial grafting on biological functions, offering simplicity, versatility, and the flexibility to select diverse substrates, grafting materials, and targeting elements for customization in a range of biomedical applications.