Bovine Hydroxyapatite-Based Bone Scaffold with Gentamicin Accelerates Vascularization and Remodeling of Bone Defect

Abstract

Osteomyelitis is an infectious disease which is also a major complication of bone defects. This study aims to determine the effect of bovine hydroxyapatite-gelatin-based bone implants with gentamicin as an antibiotic (BHA-GEL-GEN implant) on the regeneration of bone defects in vivo. The BHA-GEL-GEN and BHA-GEL implants were made by direct compression. In vivo study was carried out with Wistar rats. The rats were divided into three groups: negative control, BHA-GEL implant, and BHA-GEL-GEN implants. The defect model used was the burr hole defect model with diameter 2.2 mm and 2 mm deep. After 2, 7, 14, and 28 days, the rats were sacrificed. Bone integrity was carried out using X-ray radiography. Radiological examination was performed using haematoxylin and eosin (HE) staining and immunohistochemical techniques with anti-vascular endothelial growth factor (VEGF) and anti-alkaline phosphatase (ALP) antibodies. Based on the radiograph, the implanted group had accelerated bone growth in the defect area. Semiquantitative data from HE staining showed that the implanted group had accelerated migration of osteoclasts, osteoblasts, and osteocytes in the defect area. The immunoreactive score showed that the BHA-GEL-GEN group had higher VEGF expression compared to two other groups. The three groups did not provide a significant difference in ALP expression. In conclusion, the BHA-GEL-GEN implant causes accelerated bone defects repair by accelerating tissue vascularity and does not interfere with the bone remodeling process. Therefore, the BHA-GEL-GEN implant is potentially a biomedical material for osteomyelitis therapy.

Signaling Pathway and Transcriptional Regulation in Osteoblasts during Bone Healing: Direct Involvement of Hydroxyapatite as a Biomaterial

“…Microscale-sized HA (microHA) is the classical HA used as bone tissue scaffold. The administration of microHA was able to induce new bone growth in the defect area in vivo [9,47]. However, Chandran et al (2016) showed that the administration of microHA in osteoporotic rats did not provide a higher regeneration efficiency than the sham group [48].…”

“…HA (Ca 10 [PO 4 ] 6 [OH] 2 ) is a derivate of calcium phosphate along with tricalcium phosphate and bioglass ceramic [29]. Calcium phosphate is often used as a biomaterial for the production of bone and dental tissue implants, or as a drug delivery system targeting hard tissue [2,6,9,30]. The organic and inorganic components account for 40% and 60% of the extracellular matrix (ECM) of bone, respectively.…”

“…It is biocompatible because its chemical and physical properties resemble those of natural HA in bone [31]. The biodegradable nature of HA is attributed to its slow degradation when used in vivo, following the growth of new bone tissue [9]. Furthermore, HA also functions as a scaffold to bone tissue, making it osteoconductive, especially with collagen or gelatin.…”

“…HA is widely used because it contains similar physical and chemical components to those of natural HA present in bone tissue [2]. Moreover, studies reported that HA induced a favorable immune response [7], exerted an angiogenic effect on defective bone tissue [8,9], and activated osteoblasts and osteoclasts for bone tissue remodeling by accelerating the differentiation of these cells [10,11].…”

Fabrication and Characterization of Submicron-Scale Bovine Hydroxyapatite: A Top-Down Approach for a Natural Biomaterial

“…Carbonated HA was found to increase osteoblast proliferation in vitro [ 20 ]. Other characteristics of BHA, such as its high compressive strength, prevent premature degradation and support bone formation in vivo [ 16 , 21 ].…”