Hydroxyapatite fiber material with BMP‐2 gene induces ectopic bone formation

Abstract

Collagen containing bone morphogenetic protein-2 (BMP-2) expression vector, which is called "gene-activated matrix," promotes bone regeneration when transplanted to the bone defect. We speculated that hydroxyapatite fiber (HF) would be an ideal matrix for "gene-activated matrix" especially for bone regeneration, because it is oseteoconductive and has high affinity to DNA. The purpose of this study is to clarify whether HF containing BMP-2 expression vector induces ectopic bone formation. We prepared HF containing 0, 10, 50, and 100 microg BMP-2 expression vector. Wistar male rats (8 weeks) were used and each rat received two HF implants in the left and right dorsal muscle. The rats were sacrificed 4, 8, and 12 weeks after the operation, and implants were analyzed radiographically by softex, dual-energy X-ray absorptiometry, and they were histologically examined. At 4 weeks, HF containing 50 or 100 microg BMP-2 expression vector showed high bone mineral contents and large radiopaque volume compared to the other implants. At 8 and 12 weeks, HF containing 50 microg BMP-2 expression vector exerted the highest values in the radiographic analyses. Bonelike tissue was histologically observed in HF containing 50 and 100 microg BMP-2 expression vector groups but not detected in the other implants. The present results suggest that HF is potential as a matrix for "gene-activated matrix" for bone tissue engineering.

Combination of simvastatin and hydroxyapatite fiber induces bone augmentation

“…In this study, we showed that HAF can serve as a substance carrier by demonstrating the stable release of simvastatin from HAF/simvastatin compound materials. This is in agreement with the report by Oda et al [14], who suggested HAF as a potential component of a drug-delivery system based on its biocompatibility, biode-gradability, and cotton-like fibrous 3D structure. Importantly, the effects of HAF in bone formation have been demonstrated by using the rabbit cranium chamber model [12] and the post-extraction tooth socket model [13].…”

“…This indicates that our highest dose (0.75 mg) might not have been high enough to cause inflammatory reaction. Another curious effect of simvastatin is ectopic bone formation [14]. In our study model, in which the chamber was covered by periosteum, some mesenchymal cells could have had the chance to enter from the top of the chamber.…”

“…In recent years, pure HAF has been developed successfully, and its capacity to induce bone formation has been demonstrated [12,13]. Besides its effects on bone growth, HAF is also expected to serve as a carrier by holding substances within its three-dimensional structure and slowly releasing them-just like a drug-delivery system [14].…”

Vascular Endothelial Growth Factor Inhibits Bone Morphogenetic Protein 2 Expression in Rat Mesenchymal Stem Cells

“…For instance, the synthesis of a tissue-engineered bone construct usually requires a 6-12 week culture and seeding period. [9][10][11] These long construction times are not oncologically safe for rapidly growing malignancies. Similarly, long culture periods are a significant drawback to the use of tissueengineered constructs for traumatic defects, as they would require prolonged open wound care and convalescence.…”

Realizing the potential of gene-based molecular therapies in bone repair

“…(64) A lower (10 µg) plasmid dose was also effective but required 12 weeks to show radiopaque tissue. HA may be an optimal scaffold as the scaffold itself induced formation of calcified tissue in this study.…”