PMID- 35544769
OWN - NLM
STAT- Publisher
LR  - 20240216
IS  - 1944-8252 (Electronic)
IS  - 1944-8244 (Linking)
DP  - 2022 May 11
TI  - Engineering a Mechanoactive Fibrous Substrate with Enhanced Efficiency in 
      Regulating Stem Cell Tenodifferentiation.
LID - 10.1021/acsami.2c04294 [doi]
AB  - Electrospun-aligned fibers in ultrathin fineness have previously demonstrated a 
      limited capacity in driving stem cells to differentiate into tendon-like cells. 
      In view of the tendon's mechanoactive nature, endowing such aligned fibrous 
      structure with mechanoactivity to exert in situ mechanical stimulus by itself, 
      namely, without any forces externally applied, is likely to potentiate its 
      efficiency of tenogenic induction. To test this hypothesis, in this study, a 
      shape-memory-capable poly(l-lactide-co-caprolactone) (PLCL) copolymer was 
      electrospun into aligned fibrous form followed by a "stretching-recovery" 
      shape-programming procedure to impart shape memory capability. Thereafter, in the 
      absence of tenogenic supplements, human adipose-derived stem cells (ADSCs) were 
      cultured on the programmed fibrous substrates for a duration of 7 days, and the 
      effects of constrained recovery resultant stress-stiffening on cell morphology, 
      proliferation, and tenogenic differentiation were examined. The results indicate 
      that the in situ enacted mechanical stimulus due to shape memory effect (SME) did 
      not have adverse influence on cell viability and proliferation, but significantly 
      promoted cellular elongation along the direction of fiber alignment. Moreover, it 
      revealed that tendon-specific protein markers such as tenomodulin (TNMD) and 
      tenascin-C (TNC) and gene expression of scleraxis (SCX), TNMD, TNC, and collagen 
      I (COL I) were significantly upregulated on the mechanoactive fibrous substrate 
      with higher recovery stress compared to the counterparts. Mechanistically, the 
      Rho/ROCK signaling pathway was identified to be involved in the substrate 
      self-actuation-induced enhancement in tenodifferentiation. Together, these 
      results suggest that constrained shape recovery stress may be employed as an 
      innovative loading modality to regulate the stem cell tenodifferentiation by 
      presenting the fibrous substrate with an aligned tendon-like topographical cue 
      and an additional mechanoactivity. This newly demonstrated paradigm in modulating 
      stem cell tenodifferentiation may improve the efficacy of tendon tissue 
      engineering strategy for tendon healing and regeneration.
FAU - Guo, Xuran
AU  - Guo X
AUID- ORCID: 0000-0002-0082-5059
AD  - College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 
      Shanghai 201620, China.
AD  - Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative 
      Medicine, Donghua University, Shanghai 201620, China.
FAU - Wang, Xianliu
AU  - Wang X
AD  - College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 
      Shanghai 201620, China.
AD  - Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative 
      Medicine, Donghua University, Shanghai 201620, China.
FAU - Tang, Han
AU  - Tang H
AD  - College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 
      Shanghai 201620, China.
AD  - Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative 
      Medicine, Donghua University, Shanghai 201620, China.
FAU - Ren, Yajuan
AU  - Ren Y
AD  - Longhua Hospital affiliated to the Shanghai University of Traditional Chinese 
      Medicine, Shanghai 200032, China.
FAU - Li, Donghong
AU  - Li D
AD  - College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 
      Shanghai 201620, China.
AD  - Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative 
      Medicine, Donghua University, Shanghai 201620, China.
FAU - Yi, Bingcheng
AU  - Yi B
AUID- ORCID: 0000-0001-8056-4882
AD  - College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 
      Shanghai 201620, China.
AD  - Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital 
      affiliated to the Shanghai Jiao Tong University School of Medicine, Shanghai 
      200011, China.
FAU - Zhang, Yanzhong
AU  - Zhang Y
AUID- ORCID: 0000-0002-2663-1279
AD  - College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 
      Shanghai 201620, China.
AD  - Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative 
      Medicine, Donghua University, Shanghai 201620, China.
AD  - Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital 
      affiliated to the Shanghai Jiao Tong University School of Medicine, Shanghai 
      200011, China.
AD  - China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou 310058, China.
LA  - eng
PT  - Journal Article
DEP - 20220511
PL  - United States
TA  - ACS Appl Mater Interfaces
JT  - ACS applied materials & interfaces
JID - 101504991
SB  - IM
OTO - NOTNLM
OT  - adipose-derived stem cells
OT  - electrospinning
OT  - mechanotransduction
OT  - shape memory effect
OT  - tenogenic differentiation
EDAT- 2022/05/12 06:00
MHDA- 2022/05/12 06:00
CRDT- 2022/05/11 17:03
PHST- 2022/05/12 06:00 [pubmed]
PHST- 2022/05/12 06:00 [medline]
PHST- 2022/05/11 17:03 [entrez]
AID - 10.1021/acsami.2c04294 [doi]
PST - aheadofprint
SO  - ACS Appl Mater Interfaces. 2022 May 11. doi: 10.1021/acsami.2c04294.