PMID- 34663065 OWN - NLM STAT- MEDLINE DCOM- 20220209 LR - 20220408 IS - 1944-8252 (Electronic) IS - 1944-8244 (Print) IS - 1944-8244 (Linking) VI - 13 IP - 43 DP - 2021 Nov 3 TI - Controlled Self-Assembly of DNA-Mimicking Nanotubes to Form a Layer-by-Layer Scaffold for Homeostatic Tissue Constructs. PG - 51321-51332 LID - 10.1021/acsami.1c13345 [doi] AB - Various biomaterial scaffolds have been developed for improving stem cell anchorage and function in tissue constructs for in vitro and in vivo uses. Growth factors are typically applied to scaffolds to mediate cell differentiation. Conventionally, growth factors are not strictly localized in the scaffolds; thus, they may leak into the surrounding environment, causing undesired side effects on tissues or cells. Hence, there is a need for improved tissue construct strategies based on highly localized drug delivery and a homeostatic microenvironment. This study developed an injectable nanomatrix (NM) scaffold with a layer-by-layer structure inside each nanosized fiber of the scaffold based on controlled self-assembly at the molecular level. The NM was hierarchically assembled from Janus base nanotubes (JBNTs), matrilin-3, and transforming growth factor beta-1 (TGF-beta1) via bioaffinity. JBNTs, which form the NM backbone, are novel DNA-inspired nanomaterials that mimic the natural helical nanostructures of collagens. The chondrogenic factor, TGF-beta1, was enveloped in the inner layer inside the NM fibers to prevent its release. Matrilin-3 was incorporated into the outer layer to create a cartilage-mimicking microenvironment and to maintain tissue homeostasis. Interestingly, human mesenchymal stem cells (hMSCs) had a strong preference to anchor along the NM fibers and formed a localized homeostatic microenvironment. Therefore, this NM has successfully generated highly organized structures via molecular self-assembly and achieved localized drug delivery and stem cell anchorage for homeostatic tissue constructs. FAU - Zhou, Libo AU - Zhou L AD - Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut 06269, United States. FAU - Zhang, Wuxia AU - Zhang W AD - Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut 06269, United States. FAU - Lee, Jinhyung AU - Lee J AD - Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut 06269, United States. FAU - Kuhn, Liisa AU - Kuhn L AUID- ORCID: 0000-0003-1447-0719 AD - Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut 06269, United States. FAU - Chen, Yupeng AU - Chen Y AUID- ORCID: 0000-0001-6940-6277 AD - Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut 06269, United States. LA - eng GR - R01 AR072027/AR/NIAMS NIH HHS/United States GR - R03 AR069383/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20211019 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 0 (Biocompatible Materials) RN - 9007-49-2 (DNA) SB - IM MH - Biocompatible Materials/*chemistry MH - DNA/*chemistry MH - Drug Delivery Systems MH - Homeostasis MH - Humans MH - Mesenchymal Stem Cells/cytology MH - Models, Molecular MH - Nanotubes/*chemistry MH - Particle Size MH - Surface Properties MH - *Tissue Engineering MH - Tissue Scaffolds/*chemistry PMC - PMC8982526 MID - NIHMS1787758 OTO - NOTNLM OT - DNA nanotechnology OT - Janus base nanomatrix OT - layer-by-layer OT - self-assembly OT - tissue engineering COIS- The authors declare the following competing financial interest(s): Dr. Yupeng Chen is a co-founder of NanoDe Therapeutics, Inc. EDAT- 2021/10/20 06:00 MHDA- 2022/02/10 06:00 PMCR- 2022/04/05 CRDT- 2021/10/19 05:27 PHST- 2021/10/20 06:00 [pubmed] PHST- 2022/02/10 06:00 [medline] PHST- 2021/10/19 05:27 [entrez] PHST- 2022/04/05 00:00 [pmc-release] AID - 10.1021/acsami.1c13345 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2021 Nov 3;13(43):51321-51332. doi: 10.1021/acsami.1c13345. Epub 2021 Oct 19.