Compositions and methods for treating bone

1. A method of treating an impaired bone to facilitate strengthening and healing of bone comprising:

applying a composition to the impaired bone,

wherein

the composition consists of a matrix having incorporated therein a liquid consisting of platelet derived growth factor (PDGF) at a concentration in a range of about 0.1 mg/ml to about 1.0 mg/ml in a buffer,

the matrix is porous calcium phosphate,

the calcium phosphate has interconnected pores,

the calcium phosphate has a porosity greater than 40%, and

the calcium phosphate consists of particles in a range of about 100 μm to about 5 mm.

2. The method of claim 1 , wherein the impaired bone is a fractured bone, a diseased bone, a weakened bone, or a bone susceptible to damage due to increased load.

3. The method of claim 2 , wherein the diseased bone is a diseased vertebra.

4. The method of claim 2 , wherein the diseased bone is an osteoporotic bone.

5. The method of claim 1 , wherein the calcium phosphate has a porosity of greater than 50%.

6. The method of claim 1 , wherein the PDGF is at a concentration of about 0.3 mg/ml.

7. The method of claim 1 , wherein the bone is a humerus, ulna, radius, femur, tibia, fibula, patella, a bone of the ankle, a bone of the wrist, a bone of the hindfoot, carpal, metacarpal, phalangeal, tarsal, metatarsal, rib, sternum, vertebra, scapula, clavicle, pelvis, a craniofacial bone, or sacrum.

8. The method of claim 1 , wherein the step of applying the composition to the impaired bone comprises:

applying the composition to orthopedic hardware; and

inserting the orthopedic hardware into the bone.

9. The method of claim 1 , wherein the PDGF is PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, or PDGF-DD, or a mixture thereof.

10. The method of claim 1 , wherein the PDGF is rhPDGF-BB or a fragment thereof.

11. The method of claim 1 , wherein the calcium phosphate has a calcium/phosphorous atomic ratio ranging from 0.5 to 2.0.

12. The method of claim 1 , where the calcium phosphate is β-tricalcium phosphate.

13. The method of claim 1 , wherein the calcium phosphate consists of particles in a range of about 100 μm to about 3000 μm.

14. The method of claim 1 , wherein the calcium phosphate consists of particles in a range of about 250 μm to about 2000 μm.

15. The method of claim 1 , wherein the calcium phosphate consists of particles in a range of about 250 μm to about 1000 μm.

16. The method of claim 1 , wherein the liquid has a pH ranging from about 3.0 to about 8.0.

17. The method of claim 1 , wherein the liquid is formed by solubilizing lyophilized PDGF in water, wherein prior to solubilization the PDGF is lyophilized from an appropriate buffer.

18. The method of claim 1 , wherein the liquid consists of PDGF at a concentration in a range of about 0.2 mg/mL to about 0.75 mg/mL in a buffer.

19. The method of claim 1 , wherein the liquid consists of PDGF at a concentration in a range of about 0.25 mg/mL to about 0.5 mg/mL in a buffer.

20. The method of claim 1 , wherein the composition is resorbable such that at least 80% of the calcium phosphate is resorbed within one year of being implanted.

21. The method of claim 1 , wherein the incorporated liquid is adsorbed or absorbed to the calcium phosphate.

22. The method of claim 1 , wherein the growth factor consists of rhPDGF-BB having at least 65% of intact rhPDGF-B chain.

23. The method of claim 1 , wherein the growth factor consists of rhPDGF-BB having at least 75% of intact rhPDGF-B chain.

24. The method of claim 23 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 25% of the matrix's own weight.

25. The method of claim 24 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 50% of the matrix's own weight.

26. The method of claim 25 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 200% of the matrix's own weight.

27. The method of claim 26 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 300% of the matrix's own weight.

28. A method of treating an impaired bone to facilitate strengthening and healing of bone comprising:

applying a composition to the impaired bone,

wherein

the composition consists of a matrix having incorporated therein a liquid consisting of platelet derived growth factor (PDGF) at a concentration in a range of about 0.1 mg/ml to about 1.0 mg/ml in a buffer,

the matrix is porous calcium phosphate,

the calcium phosphate has interconnected pores,

the composition has a porosity that facilitates cell migration into the composition, and

the calcium phosphate consists of particles in a range of about 100 μm to about 5 mm.

29. The method of claim 28 , wherein said porosity is macroporosity.

30. The method of claim 28 , wherein said porosity consists of porous calcium phosphate particles having a porosity greater than 40%.

31. The method of claim 30 , wherein the calcium phosphate has a porosity of greater than 50%.

32. The method of claim 28 , wherein the impaired bone is a fractured bone, a diseased bone, a weakened bone, or a bone susceptible to damage due to increased load.

33. The method of claim 32 , wherein the diseased bone is a diseased vertebra.

34. The method of claim 32 , wherein the diseased bone is an osteoporotic bone.

35. The method of claim 28 , wherein the PDGF is at a concentration of about 0.3 mg/ml.

36. The method of claim 28 , wherein the bone is a humerus, ulna, radius, femur, tibia, fibula, patella, a bone of the ankle, a bone of the wrist, a bone of the hindfoot, carpal, metacarpal, phalangeal, tarsal, metatarsal, rib, sternum, vertebra, scapula, clavicle, pelvis, a craniofacial bone, or sacrum.

37. The method of claim 28 , wherein the step of applying the composition to the impaired bone comprises:

applying the composition to orthopedic hardware; and

inserting the orthopedic hardware into the bone.

38. The method of claim 28 , wherein the PDGF is PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, or PDGF-DD, or a mixture thereof.

39. The method of claim 28 , wherein the PDGF is rhPDGF-BB or a fragment thereof.

40. The method of claim 28 , wherein the calcium phosphate has a calcium/phosphorous atomic ratio ranging from 0.5 to 2.0.

41. The method of claim 28 , where the calcium phosphate is β-tricalcium phosphate.

42. The method of claim 28 , wherein the calcium phosphate consists of particles in a range of about 100 μm to about 3000 μm.

43. The method of claim 28 , wherein the calcium phosphate consists of particles in a range of about 250 μm to about 2000 μm.

44. The method of claim 28 , wherein the calcium phosphate consists of particles in a range of about 250 μm to about 1000 μm.

45. The method of claim 28 , wherein the liquid has a pH ranging from about 3.0 to about 8.0.

46. The method of claim 28 , wherein the liquid is formed by solubilizing lyophilized PDGF in water, wherein prior to solubilization the PDGF is lyophilized from an appropriate buffer.

47. The method of claim 28 , wherein the liquid consists of PDGF at a concentration in a range of about 0.2 mg/mL to about 0.75 mg/mL in a buffer.

48. The method of claim 28 , wherein the liquid consists of PDGF at a concentration in a range of about 0.25 mg/mL to about 0.5 mg/mL in a buffer.

49. The method of claim 28 , wherein the composition is resorbable such that at least 75% of the calcium phosphate is resorbed within one year of being implanted.

50. The method of claim 28 , wherein the incorporated liquid is adsorbed or absorbed to the calcium phosphate.

51. The method of claim 28 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 25% of the matrix's own weight.

52. The method of claim 51 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 50% of the matrix's own weight.

53. The method of claim 52 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 200% of the matrix's own weight.

54. The method of claim 53 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 300% of the matrix's own weight.

55. The method of claim 28 , wherein the growth factor consists of rhPDGF-BB having at least 65% of intact rhPDGF-B chain.

56. The method of claim 28 , wherein the growth factor consists of rhPDGF-BB having at least 75% of intact rhPDGF-B chain.

57. A method of treating an impaired bone to facilitate strengthening and healing of bone comprising:

applying a composition to the impaired bone,

wherein

the composition consists of a matrix having incorporated therein a liquid consisting of platelet derived growth factor (PDGF) at a concentration in a range of about 0.1 mg/ml to about 1.0 mg/ml in a buffer,

the matrix is porous calcium phosphate,

the calcium phosphate has interconnected pores,

the calcium phosphate consists of particles in a range of about 100 μm to about 5 mm, and

the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 25% of the matrix's own weight.

58. The method of claim 57 , wherein the impaired bone is a fractured bone, a diseased bone, a weakened bone, or a bone susceptible to damage due to increased load.

59. The method of claim 58 , wherein the diseased bone is a diseased vertebra.

60. The method of claim 58 , wherein the diseased bone is an osteoporotic bone.

61. The method of claim 58 , wherein the PDGF is at a concentration of about 0.3 mg/ml.

62. The method of claim 57 , wherein the bone is a humerus, ulna, radius, femur, tibia, fibula, patella, a bone of the ankle, a bone of the wrist, a bone of the hindfoot, carpal, metacarpal, phalangeal, tarsal, metatarsal, rib, sternum, vertebra, scapula, clavicle, pelvis, a craniofacial bone, or sacrum.

63. The method of claim 57 , wherein the step of applying the composition to the impaired bone comprises:

applying the composition to orthopedic hardware; and

inserting the orthopedic hardware into the bone.

64. The method of claim 57 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 50% of the matrix's own weight.

65. The method of claim 64 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 200% of the matrix's own weight.

66. The method of claim 65 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 300% of the matrix's own weight.

67. A method of treating an impaired bone to facilitate strengthening and healing of bone comprising:

applying a composition to the impaired bone,

wherein

the composition consists of a matrix having incorporated therein a liquid consisting of platelet derived growth factor (PDGF) at a concentration in a range of about 0.1 mg/ml to about 1.0 mg/ml in a buffer,

the matrix is porous calcium phosphate and collagen,

the calcium phosphate has interconnected pores,

the calcium phosphate has a porosity greater than 40%, and

the calcium phosphate consists of particles in a range of about 100 μm to about 5 mm.

68. The method of claim 67 , wherein the impaired bone is a fractured bone, a diseased bone, a weakened bone, or a bone susceptible to damage due to increased load.

69. The method of claim 68 , wherein the diseased bone is a diseased vertebra.

70. The method of claim 68 , wherein the diseased bone is an osteoporotic bone.

71. The method of claim 67 , wherein the calcium phosphate has a porosity of greater than 50%.

72. The method of claim 67 , wherein the PDGF is at a concentration of about 0.3 mg/ml.

73. The method of claim 67 , wherein the bone is a humerus, ulna, radius, femur, tibia, fibula, patella, a bone of the ankle, a bone of the wrist, a bone of the hindfoot, carpal, metacarpal, phalangeal, tarsal, metatarsal, rib, sternum, vertebra, scapula, clavicle, pelvis, a craniofacial bone, or sacrum.

74. The method of claim 67 , wherein the step of applying the composition to the impaired bone comprises:

applying the composition to orthopedic hardware; and

inserting the orthopedic hardware into the bone.

75. The method of claim 67 , wherein the PDGF is PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, or PDGF-DD, or a mixture thereof.

76. The method of claim 67 , wherein the PDGF is rhPDGF-BB or a fragment thereof.

77. The method of claim 67 , wherein the calcium phosphate has a calcium/phosphorous atomic ratio ranging from 0.5 to 2.0.

78. The method of claim 67 , where the calcium phosphate is β-tricalcium phosphate.

79. The method of claim 67 , wherein the calcium phosphate consists of particles in a range of about 100 μm to about 3000 μm.

80. The method of claim 67 , wherein the calcium phosphate consists of particles in a range of about 250 μm to about 2000 μm.

81. The method of claim 67 , wherein the calcium phosphate consists of particles in a range of about 250 μm to about 1000 μm.

82. The method of claim 67 , wherein the liquid has a pH ranging from about 3.0 to about 8.0.

83. The method of claim 67 , wherein the liquid is formed by solubilizing lyophilized PDGF in water, wherein prior to solubilization the PDGF is lyophilized from an appropriate buffer.

84. The method of claim 67 , wherein the liquid consists of PDGF at a concentration in a range of about 0.2 mg/mL to about 0.75 mg/mL in a buffer.

85. The method of claim 67 , wherein the liquid consists of PDGF at a concentration in a range of about 0.25 mg/mL to about 0.5 mg/mL in a buffer.

86. The method of claim 67 , wherein the composition is resorbable such that at least 80% of the calcium phosphate is resorbed within one year of being implanted.

87. The method of claim 67 , wherein the incorporated liquid is adsorbed or absorbed to the calcium phosphate.

88. The method of claim 67 , wherein the growth factor consists of rhPDGF-BB having at least 65% of intact rhPDGF-B chain.

89. The method of claim 67 , wherein the growth factor consists of rhPDGF-BB having at least 75% of intact rhPDGF-B chain.

90. The method of claim 67 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 25% of the matrix's own weight.

91. The method of claim 90 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 50% of the matrix's own weight.

92. The method of claim 91 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 200% of the matrix's own weight.

93. The method of claim 92 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 300% of the matrix's own weight.

94. A method of treating an impaired bone to facilitate strengthening and healing of bone comprising:

applying a composition to the impaired bone,

wherein

the composition consists of a matrix having incorporated therein a liquid consisting of platelet derived growth factor (PDGF) at a concentration in a range of about 0.1 mg/ml to about 1.0 mg/ml in a buffer,

the matrix is porous calcium phosphate and collagen,

the calcium phosphate has interconnected pores,

the composition has a porosity that facilitates cell migration into the composition, and

the calcium phosphate consists of particles in a range of about 100 μm to about 5 mm.

95. The method of claim 94 , wherein said porosity is macroporosity.

96. The method of claim 94 , wherein said porosity consists of porous calcium phosphate particles having a porosity greater than 40%.

97. The method of claim 96 , wherein the calcium phosphate has a porosity of greater than 50%.

98. The method of claim 94 , wherein the impaired bone is a fractured bone, a diseased bone, a weakened bone, or a bone susceptible to damage due to increased load.

99. The method of claim 98 , wherein the diseased bone is a diseased vertebra.

100. The method of claim 98 , wherein the diseased bone is an osteoporotic bone.

101. The method of claim 94 , wherein the PDGF is at a concentration of about 0.3 mg/ml.

102. The method of claim 94 , wherein the bone is a humerus, ulna, radius, femur, tibia, fibula, patella, a bone of the ankle, a bone of the wrist, a bone of the hindfoot, carpal, metacarpal, phalangeal, tarsal, metatarsal, rib, sternum, vertebra, scapula, clavicle, pelvis, a craniofacial bone, or sacrum.

103. The method of claim 94 , wherein the step of applying the composition to the impaired bone comprises:

applying the composition to orthopedic hardware; and

inserting the orthopedic hardware into the bone.

104. The method of claim 94 , wherein the PDGF is PDGF-AA, PDGF-BB, PDGF-AB, PDGF-CC, or PDGF-DD, or a mixture thereof.

105. The method of claim 94 , wherein the PDGF is rhPDGF-BB or a fragment thereof.

106. The method of claim 94 , wherein the calcium phosphate has a calcium/phosphorous atomic ratio ranging from 0.5 to 2.0.

107. The method of claim 94 , where the calcium phosphate is β-tricalcium phosphate.

108. The method of claim 94 , wherein the calcium phosphate consists of particles in a range of about 100 μm to about 3000 μm.

109. The method of claim 94 , wherein the calcium phosphate consists of particles in a range of about 250 μm to about 2000 μm.

110. The method of claim 94 , wherein the calcium phosphate consists of particles in a range of about 250 μm to about 1000 μm.

111. The method of claim 94 , wherein the liquid has a pH ranging from about 3.0 to about 8.0.

112. The method of claim 94 , wherein the liquid is formed by solubilizing lyophilized PDGF in water, wherein prior to solubilization the PDGF is lyophilized from an appropriate buffer.

113. The method of claim 94 , wherein the liquid consists of PDGF at a concentration in a range of about 0.2 mg/mL to about 0.75 mg/mL in a buffer.

114. The method of claim 94 , wherein the liquid consists of PDGF at a concentration in a range of about 0.25 mg/mL to about 0.5 mg/mL in a buffer.

115. The method of claim 94 , wherein the composition is resorbable such that at least 75% of the calcium phosphate is resorbed within one year of being implanted.

116. The method of claim 94 , wherein the incorporated liquid is adsorbed or absorbed to the calcium phosphate.

117. The method of claim 94 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 25% of the matrix's own weight.

118. The method of claim 117 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 50% of the matrix's own weight.

119. The method of claim 118 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 200% of the matrix's own weight.

120. The method of claim 119 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 300% of the matrix's own weight.

121. The method of claim 94 , wherein the growth factor consists of rhPDGF-BB having at least 65% of intact rhPDGF-B chain.

122. The method of claim 94 , wherein the growth factor consists of rhPDGF-BB having at least 75% of intact rhPDGF-B chain.

123. A method of treating an impaired bone to facilitate strengthening and healing of bone comprising:

applying a composition to the impaired bone,

wherein

the composition consists of a matrix having incorporated therein a liquid consisting of platelet derived growth factor (PDGF) at a concentration in a range of about 0.1 mg/ml to about 1.0 mg/ml in a buffer,

the matrix is porous calcium phosphate and collagen,

the calcium phosphate has interconnected pores, the calcium phosphate consists of particles in a range of about 100 μm to about 5 mm, and

the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 25% of the matrix's own weight.

124. The method of claim 123 , wherein the impaired bone is a fractured bone, a diseased bone, a weakened bone, or a bone susceptible to damage due to increased load.

125. The method of claim 124 , wherein the diseased bone is a diseased vertebra.

126. The method of claim 124 , wherein the diseased bone is an osteoporotic bone.

127. The method of claim 123 , wherein the PDGF is at a concentration of about 0.3 mg/ml.

128. The method of claim 123 , wherein the bone is a humerus, ulna, radius, femur, tibia, fibula, patella, a bone of the ankle, a bone of the wrist, a bone of the hindfoot, carpal, metacarpal, phalangeal, tarsal, metatarsal, rib, sternum, vertebra, scapula, clavicle, pelvis, a craniofacial bone, or sacrum.

129. The method of claim 123 , wherein the step of applying the composition to the impaired bone comprises:

applying the composition to orthopedic hardware; and

inserting the orthopedic hardware into the bone.

130. The method of claim 123 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 50% of the matrix's own weight.

131. The method of claim 130 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 200% of the matrix's own weight.

132. The method of claim 131 , wherein the matrix is capable of absorbing an amount of the liquid consisting of PDGF that is equal to at least about 300% of the matrix's own weight.