title: Biological properties of dehydrated human amnion/chorion composite graft: implications for chronic wound healing.
abstract: Human amnion/chorion tissue derived from the placenta is rich in cytokines and growth factors known to promote wound healing; however, preservation of the biological activities of therapeutic allografts during processing remains a challenge. In this study, PURION® (MiMedx, Marietta, GA) processed dehydrated human amnion/chorion tissue allografts (dHACM, EpiFix®, MiMedx) were evaluated for the presence of growth factors, interleukins (ILs) and tissue inhibitors of metalloproteinases (TIMPs). Enzyme-linked immunosorbent assays (ELISA) were performed on samples of dHACM and showed quantifiable levels of the following growth factors: platelet-derived growth factor-AA (PDGF-AA), PDGF-BB, transforming growth factor α (TGFα), TGFβ1, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), placental growth factor (PLGF) and granulocyte colony-stimulating factor (GCSF). The ELISA assays also confirmed the presence of IL-4, 6, 8 and 10, and TIMP 1, 2 and 4. Moreover, the relative elution of growth factors into saline from the allograft ranged from 4% to 62%, indicating that there are bound and unbound fractions of these compounds within the allograft. dHACM retained biological activities that cause human dermal fibroblast proliferation and migration of human mesenchymal stem cells (MSCs) in vitro. An in vivo mouse model showed that dHACM when tested in a skin flap model caused mesenchymal progenitor cell recruitment to the site of implantation. The results from both the in vitro and in vivo experiments clearly established that dHACM contains one or more soluble factors capable of stimulating MSC migration and recruitment. In summary, PURION® processed dHACM retains its biological activities related to wound healing, including the potential to positively affect four distinct and pivotal physiological processes intimately involved in wound healing: cell proliferation, inflammation, metalloproteinase activity and recruitment of progenitor cells. This suggests a paracrine mechanism of action for dHACM when used for wound healing applications.
authors.affiliation: MiMedx Group, Inc., Marietta, GA, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Koob
authors.forename: Robert
authors.initials: R
authors.lastname: Rennert
authors.forename: Nicole
authors.initials: N
authors.lastname: Zabek
authors.forename: Michelle
authors.initials: M
authors.lastname: Massee
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Lim
authors.forename: Johnna S
authors.initials: JS
authors.lastname: Temenoff
authors.forename: William W
authors.initials: WW
authors.lastname: Li
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Gurtner
mesh_terms: D000650:Amnion / Q000166:cytology / Q000637:transplantation*; D000818:Animals; D049109:Cell Proliferation; D002823:Chorion / Q000166:cytology / Q000637:transplantation*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D003681:Dehydration; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D033581:Stem Cell Transplantation / Q000379:methods*; D009927:Tissue and Organ Procurement / Q000379:methods*; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*
chemical_list: D016207:Cytokines
keywords: Amnion; Chorion; Chronic ulcers; Dermal fibroblasts; Growth factors; Mesenchymal stem cells; Wound healing; dHACM
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