PMID- 29522987 OWN - NLM STAT- MEDLINE DCOM- 20190823 LR - 20220408 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 165 DP - 2018 May TI - Harnessing biochemical and structural cues for tenogenic differentiation of adipose derived stem cells (ADSCs) and development of an in vitro tissue interface mimicking tendon-bone insertion graft. PG - 79-93 LID - S0142-9612(18)30148-0 [pii] LID - 10.1016/j.biomaterials.2018.02.046 [doi] AB - Tendon-bone interface tissue is extremely challenging to engineer because it exhibits complex gradients of structure, composition, biologics, and cellular phenotypes. As a step toward engineering these transitional zones, we initially analyzed how different (topographical or biological) cues affect tenogenic differentiation of adipose-derived stem cells (ADSCs). We immobilized platelet-derived growth factor - BB (PDGF-BB) using polydopamine (PD) chemistry on random and aligned nanofibers and investigated ADSC proliferation and tenogenic differentiation. Immobilized PDGF greatly enhanced the proliferation and tenogenic differentiation of ADSCs; however, nanofiber alignment had no effect. Interestingly, the PDGF immobilized aligned nanofiber group showed a synergistic effect with maximum expression of tenogenic markers for 14 days. We also generated a nanofiber surface with spatially controlled presentation of immobilized PDGF on an aligned architecture, mimicking native tendon tissue. A gradient of immobilized PDGF was able to control the phenotypic differentiation of ADSCs into tenocytes in a spatially controlled manner, as confirmed by analysis of the expression of tenogenic markers and immunofluorescence staining. We further explored the gradient formation strategy by generation of a symmetrical gradient on the nanofiber surface for the generation of a structure mimicking bone-patellar-tendon-bone with provision for gradient immobilization of PDGF and controlled mineralization. Our study reveals that, together with biochemical cues, favorable topographical cues are important for tenogenic differentiation of ADSCs, and gradient presentation of PDGF can be used as a tool for engineering stem cell-based bone-tendon interface tissues. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Madhurakkat Perikamana, Sajeesh Kumar AU - Madhurakkat Perikamana SK AD - Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. FAU - Lee, Jinkyu AU - Lee J AD - Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. FAU - Ahmad, Taufiq AU - Ahmad T AD - Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. FAU - Kim, Eun Mi AU - Kim EM AD - Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. FAU - Byun, Hayeon AU - Byun H AD - Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. FAU - Lee, Sangmin AU - Lee S AD - Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. FAU - Shin, Heungsoo AU - Shin H AD - Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea. Electronic address: hshin@hanyang.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180227 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 1B56C968OA (Becaplermin) MH - *Adipocytes/cytology MH - Becaplermin/metabolism MH - *Bone and Bones/cytology MH - Cell Differentiation MH - Cells, Cultured MH - Humans MH - Nanofibers MH - *Stem Cells/cytology MH - *Tendons/cytology MH - *Tissue Scaffolds/chemistry OTO - NOTNLM OT - Bone-tendon interface OT - Gradient surfaces OT - Platelet-derived growth factor OT - Tenogenic differentiation EDAT- 2018/03/10 06:00 MHDA- 2019/08/24 06:00 CRDT- 2018/03/10 06:00 PHST- 2017/11/28 00:00 [received] PHST- 2018/02/11 00:00 [revised] PHST- 2018/02/25 00:00 [accepted] PHST- 2018/03/10 06:00 [pubmed] PHST- 2019/08/24 06:00 [medline] PHST- 2018/03/10 06:00 [entrez] AID - S0142-9612(18)30148-0 [pii] AID - 10.1016/j.biomaterials.2018.02.046 [doi] PST - ppublish SO - Biomaterials. 2018 May;165:79-93. doi: 10.1016/j.biomaterials.2018.02.046. Epub 2018 Feb 27.