Adsorption and release of insulin-like growth factor-I on porous tricalcium phosphate implant

Abstract

Abstract:In order to develop bone substitutes, the design of biomaterials like calcium phosphate ceramic loaded with bone growth factor are of great interest. However, it is necessary to control the amount of growth factor adsorbed onto ceramics and the kinetics of its release. Radiolabeling of insulin-like growth factor-I (IGF-I) with 125-iodine ([ 125 I]-IGF-I) and its adsorption onto porous tricalcium phosphate (TCP) cylinders enabled us to establish the time-adsorption and time-release curves using various concentrations of IGF-I. The adsorption curve increased rapidly and then flattened out at 72 h; 90% of the maximum was already reached at 24 h; and 20% of the adsorbed IGF-I was released in water within 4 days. In human serum the release was faster at 82% within 4 days. In vivo evaluation on an animal model was then performed. Rabbits' bilateral femoral cylindrical bone defects were filled with the TCP cylinders, which were either carrying IGF-I or implanted alone as a control in each rabbit. Bone turnover and ceramic resorption were stimulated by IGF-I loaded TCP according to standard radiography, dual-energy X-ray absorptiometry, histology, and histomorphometry.

Binding and Release Characteristics of Insulin-Like Growth Factor-1 from a Collagen–Glycosaminoglycan Scaffold

“…For example, Laffargue et al loaded IGF-1 onto porous tricalcium phosphate cylinders via adsorption in vitro and reported significant IGF-1 release up to day 4 followed by much slower release up to day 20. 45 At the end of this experiment up to 60% of the adsorbed IGF-1 remained on these matrices, indicating a strong binding interaction. 45 Protein adsorption on to collagen membranes is mainly due to hydrogen bonding and ionic bonding between the collagen and the diffusing protein, and adsorption is proportional to both the number of sites available for binding and the protein concentration.…”

“…45 At the end of this experiment up to 60% of the adsorbed IGF-1 remained on these matrices, indicating a strong binding interaction. 45 Protein adsorption on to collagen membranes is mainly due to hydrogen bonding and ionic bonding between the collagen and the diffusing protein, and adsorption is proportional to both the number of sites available for binding and the protein concentration. 46 Previously, the uptake of IGF-1 into normal human cartilage was studied, and binding experiments indicated that the growth factor binds to proteoglycans.…”

“…44 Considering this evidence, our collagen-GAG scaffold was loaded with very high levels of IGF-1 to accomplish an initial therapeutic drug release >50 ng IGF-1/mL/day. IGF-1 delivery devices have been widely investigated, [26][27][28]35,40,41,45 but we consider the collagen-GAG scaffold used in this study to be more closely related to the articular cartilage that it is designed to replace. For example, Laffargue et al loaded IGF-1 onto porous tricalcium phosphate cylinders via adsorption in vitro and reported significant IGF-1 release up to day 4 followed by much slower release up to day 20.…”

“…The amount of IGF-1 adsorbed was approximately proportional to the loading concentration, confirming previous studies using similar scaffolds. 45 We found that at low IGF-1 loading concentrations, adsorption increased almost linearly (Fig. 2B).…”

Recombinant growth/differentiation factor‐5 (GDF‐5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic

“…5,6 However, these factors could not induce osteogenesis. In this regard, bone morphogenetic proteins (BMPs), consisting of a multiplemembered family, BMP-2 to BMP-13, can induce…”