PMID- 37947356 OWN - NLM STAT- MEDLINE DCOM- 20231129 LR - 20231205 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 17 IP - 22 DP - 2023 Nov 28 TI - Micronano Titanium Accelerates Mesenchymal Stem Cells Aging through the Activation of Senescence-Associated Secretory Phenotype. PG - 22885-22900 LID - 10.1021/acsnano.3c07807 [doi] AB - Stem cell senescence is one of the most representative events of organism aging and is responsible for many physiological abnormalities and disorders. In the scenario of orthopedic disease treatment, stem cell aging may affect the implantation outcome and even lead to operation failure. To explore whether stem cell aging will affect the osteointegration effect of titanium implant, a widely used micronano titanium (MNT) was fabricated. We first verified the expected osteointegration effect of the MNT, which could be attributed to the improvement of stem cell adhesion and osteogenic differentiation. Then, we obtained aged-derived bone marrow mesenchymal stem cells (BMSCs) and studied their biological behaviors on MNT both in vitro and in vivo. We found that compared with normal rats, MNT did not significantly improve the osteointegration in aged rats. Compared with normal rats, fewer endogenous stem cells were observed at the implant-host interface, and the expression of p21 (senescence marker) was also higher. We further confirmed that MNT promoted the nuclear localization of NF-kappaB in senescent stem cells through the activation of p38 MAPK, thereby inducing the occurrence of the senescence-associated secretory phenotype (SASP) and ultimately leading to the depletion of the stem-cell pool at the implant-host interface. However, the activation of p38 MAPK can still promote the osteogenic differentiation of nonsenescent BMSCs. These results showed an interesting paradoxical balance between osteogenesis and senescence on MNT surfaces and also provided insights for the design of orthopedic implants for aging patients. FAU - Li, Xuan AU - Li X AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - Luo, Xinxin AU - Luo X AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - He, Ye AU - He Y AD - Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, North Carolina 27708, United States. FAU - Xu, Kun AU - Xu K AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - Ding, Yao AU - Ding Y AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - Gao, Pengfei AU - Gao P AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - Tao, Bailong AU - Tao B AD - Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P. R. China. FAU - Li, Meng AU - Li M AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - Tan, Meijun AU - Tan M AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - Liu, Shaopeng AU - Liu S AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - Liu, Peng AU - Liu P AUID- ORCID: 0000-0001-9406-6024 AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. FAU - Cai, Kaiyong AU - Cai K AUID- ORCID: 0000-0001-9029-680X AD - Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University Chongqing 400044, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231110 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - D1JT611TNE (Titanium) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Rats MH - Humans MH - Animals MH - Aged MH - *Titanium/pharmacology/metabolism MH - Senescence-Associated Secretory Phenotype MH - Osteogenesis MH - Cell Differentiation MH - *Mesenchymal Stem Cells MH - p38 Mitogen-Activated Protein Kinases/metabolism/pharmacology MH - Cells, Cultured OTO - NOTNLM OT - mesenchymal stem cells OT - micronano structure OT - osteointegration OT - senescence OT - titanium implant EDAT- 2023/11/10 12:44 MHDA- 2023/11/29 06:43 CRDT- 2023/11/10 07:53 PHST- 2023/11/29 06:43 [medline] PHST- 2023/11/10 12:44 [pubmed] PHST- 2023/11/10 07:53 [entrez] AID - 10.1021/acsnano.3c07807 [doi] PST - ppublish SO - ACS Nano. 2023 Nov 28;17(22):22885-22900. doi: 10.1021/acsnano.3c07807. Epub 2023 Nov 10.