The Bone Regenerative Effect of Chitosan Microsphere-Encapsulated Growth Hormone on Bony Consolidation in Mandibular Distraction Osteogenesis in a Dog Model

Abstract

The purpose of this project was to study the effect of chitosan microsphere-encapsulated human growth hormone, which causes sustained release of chitosan and human growth hormone after implantation on early bony consolidation in distraction osteogenesis of a canine model. Forty-eight dogs were used for this study. An external distraction device was applied to the mandibular body after a vertical osteotomy, and the mandibular distraction was started 5 days after the operation at a rate of 1 mm/d up to a 10-mm distraction. The experimental group was divided into a control group (I), hyaluronic acid group (II), chitosan microsphere group (III), and chitosan microsphere-encapsulated human growth hormone group (IV). Normal saline was injected in group I. In group II, a 1-ml volume of hyaluronic acid solution was injected into the distracted area. In the group III, powder of chitosan microspheres and hGH were mixed with a 1-ml volume of hyaluronic acid to make an injectable form, and it was implanted into the distracted area. In group IV, powder of chitosan microsphere-encapsulated hGH was mixed with a 1-ml volume of hyaluronic acid. A total of 1-ml volume of the solution mix was implanted into the distracted area. Five dogs in each group (total of 20 dogs) were killed 3 weeks after completion of distraction. Twenty-eight dogs were killed at 6 weeks. Bone mineral density was 13.1% of the contralateral normal mandible at 3 weeks and 29.6% at 6 weeks in group I, 16.4% at 3 weeks and 40.4% at 6 weeks in group II, 16.6% at 3 weeks and 45.95% at 6 weeks in group III, and 29.6% at 3 weeks and 66.7% at 6 weeks in group IV. The mean three-point failure load was 16.1% in the control group, 34.7% in group II, 41.5% in group III, and 52.1% in group IV compared with the intact contralateral mandible, with statistical significance. In the histological findings, new bone was generated in all groups. In group IV, the formation of active woven bone was observed throughout the distracted area at 6 weeks. The amount of new bone formation in the distracted zone was in the order of group IV, group III, group II, and the control group. In conclusion, these findings suggest that chitosan microsphere-encapsulated hGH seems to be quite effective in early bone consolidation in distraction osteogenesis.

Biologically Active Chitosan Systems for Tissue Engineering and Regenerative Medicine

“…Growth factors were then loaded onto the scaffolds by soaking them in growth factor solutions. Chitosan micro-or nanospheres were also developed as an alternative carrier system for growth factor delivery [52][53][54]. Nevertheless, this type of factor loading generally resulted in an initial burst release followed by a short period of slow release for a few days, which is undesirable in many cases that requires a long time sustained factor release.…”

Incorporação do hormônio do crescimento humano recombinante (rhGH) em matriz de polímero biodegradável

“…Cho et al 23 demostraram, em seu estudo com distração osteogênica em mandíbulas de cães, o efeito do rhGH, encapsulado em microesferas de quitosana, comparado com ácido hialurônico 8. Micrografias da sequência das superfícies das matrizes com rhGH degradadas, com aumento de 4.000×, nos registros 1°) primeiro dia, 2°) quarto dia, 3°) sétimo dia, 4°) décimo dia.…”

71 Hemifacial Microsomia and Distraction Osteogenesis

“…94,95,96 There have been reports on the use of osteoblastlike cells derived from mesenchymal cells, platelet-rich plasma, bone morphogenetic protein-2, and growth hormones in the distraction gap, aiming at an optimization of the processes of matrix deposition and consolidation. 97,98,99 …”