Dry platelet composition

Abstract

The invention features a dry platelet composition and methods of making and using the freeze-dried platelet composition.

1 . A dry platelet composition, the composition comprising:
 a plurality of dry platelets; and   one or more inhibitors of platelet activation.   
   
   
       2 . The composition of  claim 1 , wherein the one or more inhibitors of platelet activation are selected from effectors of the cyclic adenosine monophosphate (cAMP) second messenger system, sodium channel inhibitors, and effectors of the cyclic guanosine 5′ monophosphate (cGMP) second messenger system. 
   
   
       3 . The composition of  claim 1 , wherein the one or more inhibitors of platelet activation comprise adenosine, amiloride, and sodium nitroprusside. 
   
   
       4 . The composition of  claim 3 , wherein, after hydration of the composition, the concentration in the composition: of adenosine is about 10 μM to about 1 mM; of amiloride is about 0.1 mM to about 10 mM; and of sodium nitroprusside is about 2.5 μM to about 250 μM. 
   
   
       5 . The composition of  claim 2 , wherein the effectors of the cAMP second messenger system are selected from the group consisting of iloprost, prostacyclin, prostaglandin E 2 , forskolin, cholera toxin, isoproterenol, 8-bromo cyclic adenosine monophosphate, dibutyl cyclic adenosine monophosphate, theophylline, isobutylmethyl xanthine, thyrotropin, and auranofin. 
   
   
       6 . The composition of  claim 2 , wherein the sodium channel inhibitors are selected from the group consisting of amiloride analogues, bepridil, flecamide, saxitoxin, benzamil, and prajnalium. 
   
   
       7 . The composition of  claim 2 , wherein the effectors of the cGMP second messenger system are selected from the group consisting of L-arginine, nitrous oxide, SIN-1, SIN-1A, atrial natriuretic factor, vasopressin, oxytocin, and glyceril trinitrate. 
   
   
       8 . The composition of  claim 1 , further comprising one or more cryoprotective agents 
   
   
       9 . The composition of  claim 8 , wherein the cryoprotective agents are selected from the group consisting of dimethylsulfoxide, maltodextrin, dextran, hydroxyethyl starch, glucose, polyvinyl pyrrolidone, mannitol, and combinations thereof. 
   
   
       10 . The composition of  claim 1 , further comprising dry blood plasma. 
   
   
       11 . The composition of  claim 1 , further comprising one or more extracellular matrix (ECM) components. 
   
   
       12 . The composition of  claim 11 , wherein the one or more ECM components are selected from the group consisting of collagen, elastin, fibronectin, fibrillin, laminin, decorin, fibromodulin, hyaluronic acid, and a proteoglycan. 
   
   
       13 . The composition of  claim 11 , wherein the ECM components are in particles of particulate acellular tissue matrix. 
   
   
       14 . The composition of  claim 13 , wherein the particulate acellular tissue matrix is particulate acellular dermal matrix. 
   
   
       15 . The composition of  claim 1 , wherein hydration of the dry platelet composition results in a rehydrated platelet composition with substantially the same level of at least one platelet function possessed by a sample of fresh platelets from which the dry platelet composition was derived. 
   
   
       16 . The composition of  claim 15 , wherein the at least one platelet function is the ability to aggregate. 
   
   
       17 . The composition of  claim 15 , wherein the at least one platelet function is the ability to release one or more growth factors or chemokines. 
   
   
       18 . The composition of  claim 17 , wherein the growth factors or chemokines are selected from the group consisting of transforming growth factor-β (TGF-β), members of platelet derived growth factor (PDGF) family, epidermal growth factor (EGF), members of vascular endothelial growth factor (VEGF) family, and thymosin β4. 
   
   
       19 . The composition of  claim 15 , wherein the at least one platelet function is the ability to induce cell proliferation. 
   
   
       20 . The composition of  claim 19 , wherein the cell proliferation is fibroblast proliferation. 
   
   
       21 . The composition of  claim 1 , wherein the platelets are human platelets. 
   
   
       22 . A method of making a freeze-dried platelet composition, the method comprising:
 providing a sample comprising platelets;   making a mixture comprising the platelets and one or more inhibitors of platelet activation; and   drying the mixture.   
   
   
       23 . The method of  claim 22 , wherein the one or more inhibitors of platelet activation are selected from effectors of the cAMP second messenger system, sodium channel inhibitors, and effectors of the cGMP second messenger system. 
   
   
       24 . The method of  claim 22 , wherein the one or more inhibitors of platelet activation comprise adenosine, amiloride, and sodium nitroprusside. 
   
   
       25 . The method of  claim 24 , wherein, in the mixture, the concentration of adenosine is about 10 μM to about 1 mM, the concentration of amiloride is about 0.1 mM to about 10 mM, and the concentration of sodium nitroprusside is about 2.5 μM to about 250 μM. 
   
   
       26 . The method of  claim 23 , wherein the effector of the cAMP second messenger system is selected from the group consisting of iloprost, prostacyclin, prostaglandin E 2 , forskolin, cholera toxin, isoproterenol, 8-bromo cyclic adenosine monophosphate, dibutyl cyclic adenosine monophosphate, theophylline, isobutylmethyl xanthine, thyrotropin, and auranofin. 
   
   
       27 . The method of  claim 23 , wherein the sodium channel inhibitor is selected from the group consisting of amiloride analogues, bepridil, flecamide, saxitoxin, benzamil, and prajnalium. 
   
   
       28 . The method of  claim 23 , wherein the effector of the cGMP second messenger system is selected from the group consisting of L-arginine, nitrous oxide, SIN-1, SIN-1A, atrial natriuretic factor, vasopressin, oxytocin, and glyceril trinitrate. 
   
   
       29 . The method of  claim 22 , wherein the mixture further comprises one or more cryoprotective agents. 
   
   
       30 . The method of  claim 29 , wherein the one or more cryoprotective agents are selected from the group consisting of dimethyl sulfoxide, maltodextrin, dextran, hydroxyethyl starch, glucose, polyvinyl pyrrolidone, mannitol, and combinations thereof. 
   
   
       31 . The method of  claim 22 , wherein the mixture further comprises one or more extracellular matrix (ECM) components. 
   
   
       32 . The method of  claim 31 , wherein the one or more ECM components are selected from the group consisting of collagen, elastin, fibronectin, fibrillin, laminin, decorin, fibromodulin, hyaluronic acid, and a proteoglycan. 
   
   
       33 . The method of  claim 31 , wherein the ECM components are in particles of particulate acellular tissue matrix. 
   
   
       34 . The method of  claim 33 , wherein the particulate acellular tissue matrix is particulate acellular dermal matrix. 
   
   
       35 . The method of  claim 22 , wherein the mixture further comprises blood plasma. 
   
   
       36 . The method of  claim 22 , wherein drying the mixture comprises freeze-drying the mixture. 
   
   
       37 .- 38 . (canceled) 
   
   
       39 . A method of treatment, the method comprising:
 identifying a subject that has a wound that will, or is likely to, benefit from administration of platelets; and   applying the dry platelet composition of  claim 1  to the wound.   
   
   
       40 . A method of treatment, the method comprising:
 identifying a subject that has a wound that will, or is likely to, benefit from administration of platelets;   rehydrating the dry platelet composition of  claim 1  to generate a rehydrated platelet composition; and   applying the rehydrated platelet composition to the wound.   
   
   
       41 . The method or use of  claim 40 , wherein the wound is a cutaneous wound. 
   
   
       42 . The method of  claim 41 , wherein the cutaneous wound is selected from the group consisting of a pressure ulcer, a venous stasis ulcer, a diabetic ulcer, an arterial ulcer, an injury wound, a burn wound, a complex soft tissue wound, a failed skin graft or flap, a radiation-induced wound, and a gangrenous wound. 
   
   
       43 . The method  claim 40 , wherein the wound is an internal wound. 
   
   
       44 . The method of  claim 43 , wherein the internal wound is selected from the group consisting of a contusion, a fracture, a fistula, an ulcer, and an injury wound of an internal organ.