Use of collagen sponge incorporating transforming growth factor-β1 to promote bone repair in skull defects in rabbits

Abstract

The objective of this study was to evaluate the potential of collagen sponge incorporating transforming growth factor-beta1 (TGF-beta1) to enhance bone repair. The collagen sponge was prepared by freeze-drying aqueous foamed collagen solution. Thermal cross-linking was performed in a vacuum at 140 degrees C for periods ranging from 1 to 48 h to prepare a number of fine collagen sponges. When collagen sponges incorporating 125I-labeled TGF-beta1 were placed in phosphate-buffered saline (PBS) solution at 37 degrees C, a small amount of TGF-beta1 was released for the first hour, but no further release was observed thereafter, irrespective of the amount of cross-linking time the sponges had received. Collagen sponges incorporating 125I-labeled TGF-beta1 or simply labeled with 125I were implanted into the skin on the backs of mice. The radioactivity of the 125I-labeled TGF-beta1 in the collagen sponges decreased with time; the amount of TGF-beta1 remaining dependent on the cross-linking time. The in vivo retention of TGF-beta1 was longer in those sponges that had been subjected to longer cross-linking times. The in vivo release profile of the TGF-beta1 was matched with the degradation profile of the sponges. Scanning electron microscopic observation revealed no difference in structure among sponges subjected to different cross-linking times. The TGF-beta1 immobilized in the sponges was probably released in vivo as a result of sponge biodegradation because TGF-beta1 release did not occur in in vitro conditions in which sponges did not degrade. We applied collagen sponges incorporating 0.1 microg of TGF-beta1 to skull defects in rabbits in stress-unloaded bone situations. Six weeks later, the skull defects were covered by newly formed bone, in marked contrast to the results obtained with a TGF-beta1 free empty collagen sponge and 0.1 microg of free TGF-beta1. We concluded that the collagen sponges were able to release biologically active TGF-beta1 and were a promising material for bone repair.

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

“…The majority of IGF-1 release (26%-44% of the loaded IGF-1) occurred in a rapid burst release up to 24 h. This was followed by a slow controlled release in which a further 13%-16% was released between days 1 and 14. Many studies have reported similar burst releases of growth factor from such delivery devices occurring within the first 24 h. 45,[51][52][53][54] For example, Ueda et al reported that *30% of transforming growth factor-b1 incorporated in a collagen scaffold was released into the PBS by simple diffusion within the first hour of an in vitro release test. 53 We found that the percent of IGF-1 released after 24 h depended on the initial IGF-1 loading concentration and that therefore reducing the volume or loading concentration of IGF-1 could be used to reduce the burst release from this system.…”

“…Our results demonstrated that DHT had no significant effect on the adsorption or release of IGF-1 from our scaffolds, and this may add weight to the hypothesis that IGF-1 binding is influenced by the presence of CS rather than collagen in the scaffold 47,50,56 Previous studies demonstrated that increasing the length of DHT treatment had no effect on transforming growth factor-b1 release from a collagen scaffold, but scaffolds cross-linked without DHT were not compared. 53 Our future studies will study collagen scaffolds containing different proportions of GAG to establish the role of GAGs in growth factor binding in this type of scaffold. IGF-1, insulin-like growth factor-1.…”

The Use of Natural Polymers in Tissue Engineering: A Focus on Electrospun Extracellular Matrix Analogues

“…However, the degradation rates of other polymers cannot be tailored within such a high range as that of silk. Collagen degrades between 1 to 4 weeks and sometimes longer depending on the cross-linking process [129], whereas. PCL can last within the body for more than 2 years [130].…”

Treatment of articular cartilage lesions of the knee

“…Most experimental interest is in transforming growth factor (TGF) beta (mainly 1 and 3), a potent chondrogenic with osteoinductive properties [54], and bone morphogenetic protein (BMP) (mainly 2 and 7), a potent osteogenic but which aids in chondral and osseous proliferation and differentiation [14]. BMP-7 (Osteo Progenitor-1; OP-1) was found to be a potent osteogenic factor in the treatment of tibial fracture non-union [14].…”