Versatile immobilization of mimicking peptides on additively manufactured functionalized α-amino acid based poly(ester amide)s

• α-Amino acid-based functionalized polyester amides (AA-FPEAs) were prepared. • AA-FPEAs offer biocompatibility, thermal stability and mechanical strength. • Functionalized AA-FPEAs were 3D printed via fused deposition modeling. • Functionalized AA-FPEAs show promise as versatile biomaterials for tissue engineering. • CGRGDS mimicking peptide was immobilized on AA-FPEAs with via copper-free click chemistry. α-Amino acid based polyester amides (AA-PEAs) exhibit remarkable properties, including biocompatibility, biodegradability, flexibility, thermal stability, and mechanical integrity. The incorporation of α-amino acids enhances cytocompatibility, hydrogen bonding, and favorable cell-polymer interactions, making AA-PEAs appealing for biomedical applications, notably tissue engineering. However, addressing complex tissue regeneration requires additional enhancements. Introducing biologically instructive factors, like growth factors and peptides, becomes essential to facilitate cell growth, proliferation, and differentiation. This study explores α-amino acid based functionalized polyester amides (AA-FPEAs) for their potential in tissue engineering, focusing on their underexplored role as thermoplastic resources for fused deposition modeling (FDM). Novel AA-FPEAs with alkyne moieties were synthesized and additively manufactured via FDM, highlighting their structure–property correlation. Employing a facile copper-free click chemistry strategy, we successfully attached a CGRGDS mimicking peptide to AA-FPEAs using UV light and a photoinitiator with water as a solvent. UV–Vis analysis confirmed the feasibility of the click reaction, and TOF-SIMS analysis verified CGRGDS attachment on AA-FPEA films and AM scaffolds. In vitro evaluation further demonstrated that AA-FPEAs support cell growth and proliferation, highlighting their biocompatibility. These findings underscore the potential of AA-FPEAs as versatile functionalized biomaterials for tissue engineering applications.