A method for accurate replication of complex and cell-instructive surface microtopographies

Biomaterial surface topography can modulate cellular behavior and has become a powerful tool for developing highly functional biomaterials for tissue regeneration applications. For example, grained topographies in the microstructure of calcium phosphate ceramics, such as β-tricalcium phosphates (TCPs), were shown to impact their osteoinductive properties; yet the mechanisms of action underlying interactions of these surface topographies with cells are not fully understood. Probing these types of biological mechanisms is especially challenging because of the combined effects of biomaterial surface chemistry and topography, which are difficult to deconvolute. Previously, hot embossing with an inversely replicated polydimethylsiloxane (PDMS) mold was employed to transfer the topographies of TCPs onto polymer films and investigate their cell-instructive effects independent of the substrate chemistry. This method proved successful for copying the surficial topographies of the ceramics to the polymer substrates. Here, we describe an improved replication method using nickel mold galvanoforming and nanoimprinting to create high-fidelity replicas of micro- and sub-micro-sized topographies of TCPs in thermoplastic polyurethane (TPU). Our findings indicate that using the proposed method, the topography replication depth was greatly improved in both the intermediate molds and the TPU imprints of the TCPs compared to hot embossing method with PDMS mold. This method is particularly suitable for replicating complex, naturally occurring surface topographies onto different polymer films and allows for the reliable investigation of the role of micro- and sub-micro-sized topographies on cell behavior, as well as for developing highly functional biomaterials. • Galvanoformed Ni molds accurately copy the microtopographies of calcium phosphates. • Nanoimprinting with Ni molds reliably replicates topographies in polymer films. • Microtopography replication depth affects mesenchymal stromal cell morphology.