Toshiki Yanagisawa

Bone graft granules are valuable tools for ridge area bone grafting owing to their ease of manipulation and interconnected porous structure. Guided bone regeneration (GBR) using barrier membranes is commonly used for alveolar ridge augmentation; however, the surgical procedures are technically complicated. In this study, we fabricated bioresorbable mesh domes (BMDs) using two types of Vicryl mesh (woven and knitted types) containing carbonate apatite granules. BMD samples were prepared in three groups: upper sides made from the woven type (UW) and lower sides made from the woven type (LW) (the UW/LW group), upper sides made from the woven type (UW) and lower sides made from the knitted type (LK) (the UW/LK group), and upper sides made from the knitted type (UK) and lower sides made from the knitted type (LK) (the UK/LK group). The samples were subsequently implanted into rabbit calvaria, and radiomorphometric and histological analyses were conducted. The UK/LK group exhibited enhanced appositional bone formation because the knitted mesh on the skin side prevented the infiltration of a substantial amount of fibrous tissue. This increase in bone formation could be attributed to the interaction between granules and osteoprogenitors that pass through the mesh from the host bone. Conversely, the UW/LW and UW/LK groups presented limited appositional bone formation. Compared with knitted mesh, woven mesh might tend to be absorbed over a short span, allowing fibrous tissue invasion and inhibiting new bone formation. Additionally, BMDs could retain granules in a targeted location and avoid displacement of the granules to unintended locations. Graphical Abstract

Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.

Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BMCs) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BMCs/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BMCs, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BMCs/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BMCs enclosed granules and prevent granules leakage from bone defects and BMCs could not induce unfavorable effects to forme new bone. Additionally, BMCs/Gr could keep specific amounts of granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BMCs/Gr was effective in bone regeneration and improved clinical handling.

Even though conventionally prepared octacalcium phosphate and collagen composite (OCP/Col) has exhibited excellent bone regeneration and has recently been commercialized for treating bone defects, reproducible appositional bone formation with OCP/Col has never been achieved. The present study investigated whether appositional bone formation could be achieved by altering the density of OCP/Col and applying liquid nitrogen during the preparation of OCP/Col. The prepared OCP/Col disks had eight variations and were divided into categories according to four different type of densities (1.0, 1.3, 1.7, and 2.0) of OCP/Col and two different pre‐freezing conditions of gas phase (G group: −80°C) and liquid phase (L group: −196°C). These disks were implanted into subperiosteal pockets in rodent calvaria, five samples per each eight variations. Radiomorphometric analysis was conducted at 4 and 12 weeks after implantation, and histological analysis was conducted at 12 weeks after implantation. OCP/Col samples in the L group tended to retain their height and shape and had enhanced appositional bone formation, whereas OCP/Col samples in the G group tended to lose their height and shape and had limited appositional bone formation. The appositional bone formation increased along with growing density of OCP/Col, and L2.0 demonstrated higher appositional bone formation than other samples. These results suggest that the pre‐freezing conditions and densities of OCP/Col affect the appositional bone formation.

Objective This study investigated the bone regenerative properties of an octacalcium phosphate collagen composite (OCP/Col) in a rat calvarial bone defect model. Design An OCP/Col or β‐tricalcium phosphate (β‐TCP)/Col disk was implanted into the critical‐sized calvarial defects and fixed 2 or 4 weeks later. The radiopacity of defects was examined after disk implantation by the radiographic examination and micro‐computed tomography (μ‐CT). Immunohistochemical and histochemical analyses were carried out to assess the bone matrix maturation, neovascularization, and osteoclast and osteoblast distribution in the neonatal bone. Results Radiographic and μ‐CT examination of the area of implanted OCP/Col indicated the newly formed bone and no difference from those of the original bone. Osteopontin, osteocalcin, Runt‐related transcription factor 2, type 1 collagen, vascular endothelial growth factor, and alkaline phosphatase or tartrate‐resistant acid phosphatase in the newly formed calvarial bone and the surrounding connective tissue were detected by immunohistochemistry and histochemistry. Biomarker expression was not significantly elevated at the defect site; the area of which was calculated by dividing the distance from the healthy bone margin or calvarium and dura mater surface. There was no difference in the expression of these biomarkers in the OCP/Col group at 2 and 4 weeks after surgery. In addition, the expression levels of all markers were higher in the OCP/Col group than in the β‐TCP/Col group at 2 and 4 weeks after surgery. Conclusions The OCP/Col as a bone regeneration material not only exhibits osteoconductive activity that is dependent on residual healthy bone tissue, but also has osteoinductive capacity, which promotes angiogenesis and osteogenic cell invasion from host tissue into the bone defect.