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Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Maturation State and Matrix Microstructure Regulate Interstitial Cell Migration in Dense Connective Tissues
Scientific reports, v 8(1), pp 3295-13
19 Feb 2018
PMCID: PMC5818574
PMID: 29459687
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in fetal tissues with an immature extracellular matrix (ECM) that is conducive to cell migration, and that this process fails in adults due to the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a platform, we evaluated the evolving micromechanics and microstructure of fetal and adult tissues, and interrogated the interstitial migratory capacity of adult meniscal cells through fetal and adult tissue microenvironments with or without partial enzymatic digestion. To integrate our findings, a computational model was implemented to determine how changing biophysical parameters impact cell migration through these dense networks. Our results show that the micromechanics and microstructure of the adult meniscus ECM sterically hinder cell mobility, and that modulation of these ECM attributes via an exogenous matrix-degrading enzyme permits migration through this otherwise impenetrable network. By addressing the inherent limitations to repair imposed by the mature ECM, these studies may define new clinical strategies to promote repair of damaged dense connective tissues in adults.
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Details
- Title
- Maturation State and Matrix Microstructure Regulate Interstitial Cell Migration in Dense Connective Tissues
- Creators
- Feini Qu - University of PennsylvaniaQing Li - Drexel UniversityXiao Wang - University of PennsylvaniaXuan Cao - University of PennsylvaniaMiltiadis H Zgonis - University of PennsylvaniaJohn L Esterhai - University of PennsylvaniaVivek B Shenoy - University of PennsylvaniaLin Han - School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, 19104, USARobert L Mauck - University of Pennsylvania
- Publication Details
- Scientific reports, v 8(1), pp 3295-13
- Publisher
- Springer Nature
- Grant note
- R21 AR066824 / NIAMS NIH HHS P30 AR050950 / NIAMS NIH HHS I01 RX000174 / RRD VA T32 AR007132 / NIAMS NIH HHS P30 AR069619 / NIAMS NIH HHS R01 AR056624 / NIAMS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000425380900078
- Scopus ID
- 2-s2.0-85042224098
- Other Identifier
- 991019168732304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Multidisciplinary Sciences