Journal
ACTA BIOMATERIALIA
Volume 9, Issue 5, Pages 6393-6402Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2013.01.016
Keywords
Drug delivery; Enzyme; Meniscus tear; Nanofibrous scaffold; Wound healing
Funding
- National Institutes of Health [R01 AR056624, MSTP T32 GM007170]
- Department of Veterans Affairs [I01 RX000174]
- Penn Center for Musculoskeletal Disorders
- Institute for Regenerative Medicine at the University of Pennsylvania
- Musculoskeletal Transplant Foundation
- Armour-Lewis Foundation
- School of Veterinary Medicine at the University of Pennsylvania
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Endogenous repair of fibrous connective tissues is limited, and there exist few successful strategies to improve healing after injury. As such, new methods that advance repair by promoting cell growth, extracellular matrix (ECM) production, and tissue integration would represent a marked clinical advance. Using the meniscus as a test platform, we sought to develop an enzyme-releasing scaffold that enhances integrative repair. We hypothesized that the high ECM density and low cellularity of native tissue present physical and biological barriers to endogenous healing, and that localized collagenase treatment might expedite cell migration to the wound edge and tissue remodeling. To test this hypothesis, we fabricated a delivery system in which collagenase was stored inside electrospun poly(ethylene oxide) (PEO) nanofibers and released upon hydration. In vitro results showed that partial digestion of the wound interface improved repair by creating a microenvironment that facilitated cell migration, proliferation and matrix deposition. Specifically, treatment with high-dose collagenase led to a 2-fold increase in cell density at the wound margin and a 2-fold increase in integrative tissue compared to untreated controls at 4 weeks (P <= 0.05). Furthermore, when composite scaffolds containing both collagenase-releasing and structural fiber fractions were placed inside meniscal tears in vitro, enzyme release acted locally and resulted in a positive cellular response similar to that of global treatment with aqueous collagenase. This innovative approach to targeted enzyme delivery may aid the many patients that exhibit meniscal tears by promoting integration of the defect, thereby circumventing the pathologic consequences of partial meniscus removal, and may find widespread application in the treatment of injuries to a variety of dense connective tissues. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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