Abstract
This work evaluated the bone-forming potential of the platelet-derived growth factor isoform BB (PDGF-BB), insulin-like growth factor I (IGF-I), and mixed PDGF-BB/IGF-I delivered in liposomes compared with phosphate buffered saline (PBS), in the healing process of rat tooth sockets. One hundred and twelve Wistar rats were randomized into 7 groups of 16 animals each and were evaluated at 3, 7, 14 and 21 days after extraction of the maxillary second molars. The left sockets were treated with PBS (P), empty liposome (L), IGF-I in PBS (IP), IGF-I in liposome (IL), PDGF-BB in PBS (PDP), PDGF-BB in liposome (PDL) and both growth factors (GFs) together within liposomes (PDIL). The right sockets were filled with blood clot (BC). Histological and histomorphometric analyses were used to evaluate the formation of new bone and blood vessels. Immunohistochemistry was performed to evaluate the expression of osteocalcin and vascular endothelial growth factor (VEGF) during bone repair. Data were tested statistically using a Tukey's test according to a Dunn's analysis and Mann-Whitney U test followed by Kruskal-Wallis one-way analysis. Results were considered significant when p<0.05. A significantly higher percentage of bone trabeculae and a higher number of blood vessels were observed in the IL, PDL and PDIL groups (p<0.05). However, these GF-liposome groups had statistically similar results. Immunohistochemical assays first detected osteocalcin and VEGF expression at 3 days followed by a peak at 7 days. Lower immunoreactivity levels were observed in the BC, L, P, IP and PDP groups compared with the IL, PDL and PDIL groups (p<0.05). The results suggest that GFs carried by liposomes, either in isolated or mixed forms, enhanced the healing process in rat tooth sockets. The differential expression of the osteogenic markers VEGF and osteocalcin in the early phases of bone healing support these findings.
Highlights
After tooth extraction, alveolar bone resorption is followed by size and shape remodeling [1] and leads to progressive and irreversible reduction in the height and width of the alveolar ridge, which can cause problems for dental implant placement
insulin-like growth factor (IGF) plays an essential role in the general growth and maintenance of the body bone frame, by promoting local differentiation of bone cells and stimulating osteogenesis by the activation of the osteocalcin promoter, a protein secreted by osteoblasts that plays a role in mineralization, as well as it works as a negative regulator of bone formation
The liposomes were obtained by sonication, using a solution of 12.0 mg/mL dipalmitoyl phosphatidyl choline (DPPC) and 1.2 mg/mL lysophosphatidyl choline (LPC) dissolved in 4 mL of chloroform and 10 μL of PDGFBB or insulin-like growth factor I (IGF-I) solution, to produce homogeneous unilamellar vesicles with an approximately 100 nm diameter
Summary
Alveolar bone resorption is followed by size and shape remodeling [1] and leads to progressive and irreversible reduction in the height and width of the alveolar ridge, which can cause problems for dental implant placement. Growth factors (GFs) are proteins responsible for regulating the cellular stages of tissue regeneration [4,5]. IGF is an important factor for tissue regeneration. IGF plays an essential role in the general growth and maintenance of the body bone frame, by promoting local differentiation of bone cells and stimulating osteogenesis by the activation of the osteocalcin promoter, a protein secreted by osteoblasts that plays a role in mineralization, as well as it works as a negative regulator of bone formation. IGF-I has been shown to promote the differentiation of bone cells in autocrine and paracrine fashions [4,7]
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