Bone Regeneration Capacity of Newly Developed Uncalcined/Unsintered Hydroxyapatite and Poly-l-lactide-co-glycolide Sheet in Maxillofacial Surgery: An In Vivo Study

Abstract

Uncalcined/unsintered hydroxyapatite and poly-l-lactide-co-glycolide (u-HA/PLLA/PGA) is a new bioresorbable nanomaterial with superior characteristics compared with current bioresorbable materials, including appropriate mechanical properties, outstanding bioactive/osteoconductive features, and remarkably shorter resorption time. Nevertheless, the bone regeneration characteristics of this nanomaterial have not been evaluated in maxillofacial reconstructive surgery. In this study, we used a rat mandible model to assess the bone regeneration ability of u-HA/PLLA/PGA material, compared with uncalcined/unsintered hydroxyapatite and poly-l-lactide acid (u-HA/PLLA) material, which has demonstrated excellent bone regenerative ability. A 4-mm-diameter defect was created at the mandibular angle area in 28 Sprague Dawley male rats. The rats were divided into three groups: u-HA/PLLA/PGA (u-HA/PLLA/PGA graft + defect), u-HA/PLLA (u-HA/PLLA graft + defect), and sham control (defect alone). At 1, 3, 8, and 16 weeks after surgeries, the rats were sacrificed and assessed by micro-computed tomography, histological analysis with hematoxylin and eosin staining, and immunohistochemical analyses. The results confirmed that the accelerated bone bioactive/regenerative osteoconduction of u-HA/PLLA/PGA was comparable with that of u-HA/PLLA in the rat mandible model. Furthermore, this new regenerative nanomaterial was able to more rapidly induce bone formation in the early stage and had great potential for further clinical applications in maxillofacial reconstructive surgery.

Bioactive Regeneration Potential of the Newly Developed Uncalcined/Unsintered Hydroxyapatite and Poly-l-Lactide-Co-Glycolide Biomaterial in Maxillofacial Reconstructive Surgery: An In Vivo Preliminary Study

“…However, the amount of newly formed regenerative bone in the u-HA/PLLA/PGA subgroup was almost equal to or greater than that in the u-HA/PLLA subgroup, although the difference was not statistically significant (Figure 6). This phenomenon was also observed in a previous study comparing u-HA/PLLA and u-HA/PLLA/PGA in a mandibular defect model [19]. In the present study, we compared OCN expression between two materials by IHC staining.…”

“…Moreover, the presence of u-HA particles in the new composite implies that u-HA/PLLA/PGA devices will also show similar bioactive osteoconductivity. The results of our previous study showed that u-HA/PLLA/PGA and u-HA/PLLA had comparable osteoconductive abilities in a rat mandibular defect model [ 19 ], confirming the potential applicability of this material to the maxillofacial region. According to immunohistochemical (IHC) analysis of Runx2 and LepR expression, bone marrow is the main source of osteoblastic cells [ 19 ].…”

“…The results of our previous study showed that u-HA/PLLA/PGA and u-HA/PLLA had comparable osteoconductive abilities in a rat mandibular defect model [ 19 ], confirming the potential applicability of this material to the maxillofacial region. According to immunohistochemical (IHC) analysis of Runx2 and LepR expression, bone marrow is the main source of osteoblastic cells [ 19 ]. However, numerous investigations have indicated that periosteum, the tissue located along the outer surface of the bone, is another local source of skeletal stem cells for regenerative bone healing [ 22 , 23 , 24 ].…”

“…Then, the mandibular angle was covered buccally with either a u-HA/PLLA/PGA sheet or a u-HA/PLLA sheet, as follows: each rat in the material group received one u-HA/PLLA/PGA sheet on the right side and one u-HA/PLLA sheet on the left side. The sheets were fixed in place with hemoclips, as previously described ( Figure 1 C) [ 19 ]. In the sham control group, the mandibular angles were not covered.…”

“…Recently, a “fourth generation” bioresorbable material has been introduced to overcome the limitations of the u-HA/PLLA composite [ 19 ]. This material, composed of polymer and bioceramic materials, was developed with the goal of maintaining the bioactive features of u-HA/PLLA while reducing the resorption time.…”