Anticoagulants Interfere With the Angiogenic and Regenerative Responses Mediated by Platelets

Area of Science:

• Regenerative Medicine
• Biomaterials Science
• Wound Healing Research

Background:

• Platelet-rich plasma (PRP) is utilized in regenerative medicine for its growth factors.
• Citrate-based anticoagulants (acid-citrate-dextrose [ACD] and sodium citrate [SC]) are used in PRP preparation.
• Adverse reactions to citrate in PRP suggest potential interference with regenerative properties.

Purpose of the Study:

• To investigate the impact of ACD and SC anticoagulants on platelet-mediated angiogenic and regenerative responses.
• To determine if anticoagulant effects on PRP are localized and interfere with therapeutic potential.
• To compare the efficacy of SC versus ACD in supporting endothelial cell function and wound healing.

Main Methods:

• PRP was prepared from blood anticoagulated with either SC or ACD.
• Platelets were lysed to obtain PRP releasates (PRPr) for *in vitro* and *in vivo* testing.
• *In vitro* assays assessed endothelial cell proliferation and migration; *in vivo* studies evaluated mouse skin wound regeneration.

Main Results:

• Calcium (CaCl2) restitution normalized endothelial cell morphology but only SC-PRPr markedly induced angiogenic responses.
• PRP without calcium delayed wound healing; SC-PRPr with calcium promoted healing, unlike ACD-PRPr.
• ACD-PRPr induced inflammation and impaired regeneration, effects mimicked by dextrose in SC-PRPr; reduced SC concentration improved PRP efficacy.

Conclusions:

• Calcium restitution is crucial to mitigate anticoagulant-induced alterations in PRP.
• Dextrose in ACD confers anti-angiogenic, anti-regenerative, and pro-inflammatory properties to PRP.
• Using half the standard concentration of SC enhances PRP's angiogenic and regenerative capabilities.