Incorporation of the Amniotic Membrane as an Immunomodulatory Design Element in Collagen Scaffolds for Tendon Repair

Rebecca A. Hortensius, Jill H. Ebens, Marley J. Dewey, Brendan A.C. Harley

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Tendon injuries often require surgical intervention and even then result in poor outcomes due to scar formation and repeated failure. Biomaterial implants offer the potential to address multiple underlying concerns preventing improved tendon repair. Here, we describe modifications to the composition of an anisotropic collagen-glycosaminoglycan (CG) scaffold biomaterial, incorporating amniotic membrane (AM)-derived matrix to alter the inflammatory response and establish conditions for improved regenerative repair. We explored two methods of AM matrix incorporation to address multiple concerns associated with tendon repair. Amniotic membrane-derived matrix was incorporated directly into the scaffold microstructure during fabrication to form a C/AM composite. Alternatively, decellularized amniotic matrix was wrapped around the traditional collagen-chondroitin sulfate (C/CS) scaffold to form a core-shell composite (C/CS plus AM wrap) in a manner similar to current collagen membrane wraps used in rotator cuff and Achilles tendon surgeries to improve the mechanical strength of the repair. Human mesenchymal stem cells (MSCs) cultured within these materials were evaluated for metabolic health and immunomodulatory gene expression in response to inflammatory media challenge of interleukin 1 β and tumor necrosis factor α. The scaffolds were able to maintain MSC metabolic activity in all media conditions over the course of a 7 day culture. Expression of genes encoding for pro-inflammatory cytokines were down-regulated in AM containing scaffolds, suggesting the potential to employ AM-modified CG scaffolds for tendon-repair applications.

Original languageEnglish (US)
Pages (from-to)4367-4377
Number of pages11
JournalACS Biomaterials Science and Engineering
Volume4
Issue number12
DOIs
StatePublished - Dec 10 2018

Bibliographical note

Funding Information:
The authors acknowledge Dr. Sandra McMasters (SCS, UIUC) for culture media preparation, Cate Wallace (Beckman Institute, UIUC) for assistance with SEM imaging, the IGB Core Facilities for assistance with real-time PCR, and Aidan Gilchrist for assistance with mechanical testing. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award no. R03 AR062811, as well as the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award no. R01 DK099528. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Keywords

  • amniotic membrane
  • collagen
  • composite
  • inflammation
  • strength

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