Wound-healing properties of trehalose-stabilized freeze-dried outdated platelets.
BACKGROUND
The wound-healing applications of platelet (PLT)-derived cytokines, proteins, and membranes is accepted but continues to be investigated. In this study, it is demonstrated that stabilized freeze-dried PLTs prepared from outdated PLTs (FDPOs) accelerate wound healing and form tube structures as well as stabilized indated freeze-dried PLTs (FDPIs) and room-temperature fresh PLTs (RT-PLTs).


METHODS
Experiments were designed to compare in vitro and in vivo wound-healing properties of FDPI, FDPO, and RT-PLT preparations. The concentration of PLT-derived growth factor (PDGF)-betabeta and transforming growth factor (TGF)-beta1 was determined, and the abilities of FDPIs, FDPOs and RT-PLTs to induce endothelial cell proliferation and promote endothelial cell tube formation (cells formed solid spouts connecting neighboring cells to form tube structures) were observed. Wound-healing characteristics were measured by surgically inducing 1-cm(2), full-thickness wounds on db/db mice (n = 10 per group). The wounds were treated with single or multiple doses of FDPIs and FDPOs. Wound closure rate was determined, and histology samples were evaluated for cellular makeup.


RESULTS
FDPOs retained the same levels of PDGF-betabeta and TGF-beta1 and were able to promote endothelial cell proliferation and tube formation in vitro as well as FDPIs or RT-PLTs. Multiple applications of FDPO accelerated wound closure and enhanced reepithelialization when compared to untreated wounds in db/db mice.


CONCLUSIONS
FDPOs enhanced wound healing in db/db mice as well as FDPIs and RT-PLTs. Wound closure was obtained 6 days earlier than untreated wounds and histologic examination revealed reduced granulation and increased cellular angiogenesis.
Sum
Ruth
R
From Adlyfe Inc., and Cellphire Inc., Rockville, Maryland 22101, USA.
Hager
Sarah
S
Pietramaggiori
Giorgio
G
Orgill
Dennis P
DP
Dee
Josh
J
Rudolph
Alan
A
Orser
Cindy
C
Fitzpatrick
G Michael
GM
Ho
David
D
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001793:Blood Preservation / Q000379:methods; D049109:Cell Proliferation; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology; D005612:Freeze Drying / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D017713:Platelet Transfusion / Q000379:methods; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014199:Trehalose / Q000494:pharmacology*; D014945:Wound Healing
D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; D014199:Trehalose