Bio-Design and Manufacturing (2022) 5:451–464 https://doi.org/10.1007/s42242-022-00190-7 RESEARCH ARTICLE Customizable design of multiple-biomolecule delivery platform for enhanced osteogenic responses via ‘tailored assembly system’ Hyun Lee 1,2 · Min-Kyu Lee 3,4 · Ginam Han 1,2 · Hyoun-Ee Kim 3,5 · Juha Song 6 · Yuhyeon Na 1,2 · Chang-Bun Yoon 7 · SeKwon Oh 8 · Tae-Sik Jang 9 · Hyun-Do Jung 1,2 Received: 1 September 2021 / Accepted: 6 February 2022 / Published online: 24 March 2022 © Zhejiang University Press 2022 Abstract Porous titanium (Ti) scaffolds have been extensively utilized as bone substitute scaffolds due to their superior biocompatibility and excellent mechanical properties. However, naturally formed TiO 2 on the surface limits fast osseointegration. Different biomolecules have been widely utilized to overcome this issue; however, homogeneous porous Ti scaffolds could not simul- taneously deliver multiple biomolecules that have different release behaviors. In this study, functionally graded porous Ti scaffolds (FGPTs) with dense inner and porous outer parts were fabricated using a two-body combination and densification procedure. FGPTs with growth factor (BMP-2) and antibiotics (TCH) exhibited suitable mechanical properties as bone sub- stituting material and presented good structural stability. The release of BMP-2 was considerably prolonged, whereas the release of TCH was comparable to that of homogenous porous titanium scaffolds (control group). The osteogenic differen- tiation obtained using FGPTs was maintained due to the prolonged release of BMP-2. The antimicrobial properties of these scaffolds were verified using S. aureus in terms of prior release time. In addition, various candidates for graded porous Ti scaffolds with altered pore characteristics were presented. B Tae-Sik Jang tsjang@chosun.ac.kr B Hyun-Do Jung hdjung@catholic.ac.kr 1 Department of Biomedical-Chemical Engineering, Catholic University of Korea, Bucheon 14662, Republic of Korea 2 Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea 3 Department of Materials Science and Engineering, Seoul National University, Seoul 08826, Republic of Korea 4 Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, IL 60208, USA 5 Biomedical Implant Convergence Research Center, Advanced Institutes of Convergence Technology, Suwon 443-270, Republic of Korea 6 School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457, Singapore 7 Department of Advanced Materials Engineering, Korea Polytechnic University, Siheung-si, Gyeonggi-do 15073, Republic of Korea 8 Surface R&D Group, Korea Institute of Industrial Technology, Incheon 21999, Republic of Korea 9 Department of Materials Science and Engineering, Chosun University, Gwangju 61452, Republic of Korea 123