Teriparatide with Octacalcium Phosphate Collagen Composite Stimulates Osteogenic Factors.

Octacalcium phosphate and collagen composite (OCPcol) promotes osteogenic differentiation and angiogenesis, thereby enhancing bone regeneration. Although a newly developed freeze-dried composite of OCPcol and teriparatide (OCPcolTPTD) reinforced bone regeneration more than OCPcol, the mechanism of bone regeneration remains unresolved. In this study, disks containing OCPcolTPTD, OCPcol, or ß-tricalcium phosphate (ß-TCP) col were inserted into rodents with calvarial bone defects, before euthanasia 4 weeks later. Immunohistochemical and histochemical analyses were performed on bone samples to evaluate bone matrix development, angiogenesis, and osteoclast and osteoblast localization. In the OCPcolTPTD and OCPcol groups, bone regeneration was observed at the surface of calvarial dura mater and around acidophilic granular cells with abundant collagenous fiber-containing cells. Furthermore, the newly formed bone in the OCPcolTPTD group showed a larger total area and individual separated area than the other groups. Various osteogenic proteins were detected in the regenerated bone and peri-bone tissues by histochemistry and immunohistochemistry. Although the expression of several osteogenic biomarkers in the OCPcolTPTD group after 4 weeks of implantation was significantly lower than that in the OCPcol group, new bone formation by OCPcolTPTD in the center of the defect, where bone regeneration is difficult, tended to be superior to that by OCPcol. These results suggest that OCPcolTPTD enhanced bone regeneration more evenly and homogenously than OCPcol. Impact statement Our study suggests that octacalcium phosphate and collagen (OCPcol) together with a TPTD enhances bone regeneration in rodents with calvarial bone defects. Furthermore, we believe that composite of OCPcol and teriparatide (OCPcolTPTD) could be developed into novel clinical technique for the regeneration or repair of bone.

Segmental Bone Reconstruction by Octacalcium Phosphate Collagen Composites with Teriparatide.

Octacalcium phosphate and collagen composite (OCPcol) demonstrated superior bone regeneration and has been commercialized recently in Japan. Teriparatide (TPTD) is a bioactive recombinant form of parathyroid hormone that is approved for osteoporosis treatment. Because mandibular bone reconstruction after segmental resection is a key clinical problem, it was examined whether single-dose local administration of OCPcol with TPTD can affect recovery after this procedure. OCPcol was prepared, and a commercially available hydroxyapatite and collagen composite (HAPcol) was used as a control. A 15 mm length segmental bone defect was made in the mandibular region of male beagle dogs. The experimental animals were divided in four groups. OCPcol treated with TPTD (OCPcol + TPTD), OCPcol, HAPcol treated with TPTD (HAPcol + TPTD), or HAPcol was implanted into the defect. The radiopaque areas of the implanted site were measured and statistically analyzed, and histological examination was performed after 6 months. The value of radiopaque area in total region of OCPcol + TPTD was highest (90.8 ± 7.3 mm2), followed in order by OCPcol (49.3 ± 21.8 mm2), HAPcol + TPTD (10.6 ± 2.3 mm2), and HAPcol (6.4 ± 2.3 mm2), and that of OCPcol + TPTD was significantly higher than that of HAPcol + TPTD or HAPcol. All segmented mandibles of OCPcol + TPTD and a part of those of OCPcol were bridged with newly formed bone, whereas no bone bridges were observed in HAPcol + TPTD or HAPcol. These results suggested that OCPcol treated with TPTD enabled bone reconstruction after segmental mandibular resection more than other three groups.

Florid Cemento-Osseous Dysplasia-Associated Simple Bone Cyst Showing Marked Irregular Border and High Apparent Diffusion Coefficient Value.

A simple bone cyst (SBC) is an intrabone cavity without epithelial lining, which occasionally occur with fibrous-osseous lesions. The imaging finding of the scalloped border and conserving the lamina dura, periodontal ligament spaces, or follicular spaces are considered radiographically pathognomonic of SBC. SBC has been reported to occur with fibrous-osseous lesions, including cemento-osseous dysplasia (COD). Computed tomography (CT) imaging findings are sparse, and there are no reports of magnetic resonance imaging (MRI) findings, including apparent diffusion coefficient (ADC) value calculated by diffusion-weighted MRI for the florid COD-associated SBC. We report a case of a 39-year-old woman who was referred to our hospital because a panoramic radiograph of her right mandible showed asymptomatic radiolucency in the apical molar area. CT images showed a low-density lesion in the periapical areas of the right mandible, which accompanied a well-defined, high-density lesion, and a mixed low/high-density lesion with an unusual marked irregular border in the left mandible. The MRI showed cyst-like extremely hyperintense signals on fat-suppressed T2-weighted images at the right mandibular low-density and the left mandibular mixed low/high-density areas. ADC map showed high values (over 2.5 × 10-3 mm2/s) at the cystic areas in the bilateral mandible. We performed incisional biopsies of the bilateral mandibular lesions and resections of the bilateral maxillary lesions. Surgical and histopathological findings established a diagnosis of florid COD in the bilateral mandible and maxilla, simultaneously complicated by multiple SBCs in the bilateral mandible. The ADC value of cystic component is useful for the diagnosis, if the COD-associated SBC exhibits solitary, nonspecific, or rare imaging findings.

Octacalcium phosphate collagen composite stimulates the expression and activity of osteogenic factors to promote bone regeneration.

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 ß-tricalcium phosphate (ß-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 ß-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.

Efficacy of Octacalcium Phosphate Collagen Composite for Titanium Dental Implants in Dogs.

BACKGROUND: Previous studies showed that octacalcium (OCP) collagen composite (OCP/Col) can be used to repair human jaw bone defects without any associated abnormalities. The present study investigated whether OCP/Col could be applied to dental implant treatment using a dog tooth extraction socket model. METHODS: The premolars of dogs were extracted; each extraction socket was extended, and titanium dental implants were placed in each socket. OCP/Col was inserted in the space around a titanium dental implant. Autologous bone was used to fill the other sockets, while the untreated socket (i.e., no bone substitute material) served as a control. Three months after the operation, these specimens were analyzed for the osseointegration of each bone substitute material with the surface of the titanium dental implant. RESULTS: In histomorphometric analyses, the peri-implant bone areas (BA%) and bone-implant contact (BIC%) were measured. There was no difference in BA% or BIC% between OCP/Col and autologous bone. CONCLUSION: These results suggested that OCP/Col could be used for implant treatment as a bone substitute.

Clinical evaluations of complete autologous fibrin glue, produced by the CryoSeal® FS system, and polyglycolic acid sheets as wound coverings after oral surgery.

The CryoSeal® FS System has been recently introduced as an automated device for the production of complete fibrin glue from autologous plasma, rather than from pool allogenic or cattle blood, to prevent viral infection and allergic reaction. We evaluated the effectiveness of complete autologous fibrin glue and polyglycolic acid (PGA) sheet wound coverings in mucosa defect oral surgery. Postoperative pain, scar contracture, ingestion, tongue dyskinesia, and postoperative bleeding were evaluated in 12 patients who underwent oral (including the tongue) mucosa excision, and received a PGA sheet and an autologous fibrin glue covering. They were compared with 12 patients who received a PGA sheet and commercial allogenic fibrin glue. All cases in the complete autologous fibrin glue group demonstrated good wound healing without complications such as local infection or incomplete cure. All evaluated clinical measures in this group were similar or superior to the commercial allogenic fibrin glue group. Coagulation and adhesion quality achieved with this method was comparable to that with a PGA sheet and commercial fibrin glue. Covering oral surgery wounds with complete autologous fibrin glue produced by an automated device was convenient, safe, and reduced the risk of viral infection and allergic reaction associated with conventional techniques.

Orthotopic Osteogenecity Enhanced by a Porous Gelatin Sponge in a Critical-Sized Rat Calvaria Defect.

The gelatin (Gel) powders, derived from acidic and basic extractions of porcine dermis (referred to as AE and BE), were processed for the porous sponge preparation. The disks, which were less than or greater than 500 µm in diameter [small (S) and large (L) pores, respectively] in both extractions and had an interconnected structure respectively, were implanted in critical-sized defects (CSD) of rat calvaria for 4 and 8 weeks to analyze the bone repair capability. Only the AE-S disk induced bone formation (over 60%) histomorphometrically in the CSD after 8 weeks, although the collagen orientation of the regenerated bone was still immature. Osteoblastic cell culture until 14 days did not substantiate marked superiority of AE-S disk regarding the proliferation and the differentiation, although the initial attachment was enhanced on AE-S disk than BE-L disk. The results provide the findings that a Gel sponge with a specific porous structure is capable of inducing orthotopic bone formation in vivo environment.

The role of an octacalcium phosphate in the re-formation of infraspinatus tendon insertion.

BACKGROUND: To improve the success rate of rotator cuff repair, we investigated whether octacalcium phosphate (OCP) with gelatin (Gel) vehicle had a positive effect on tendon-to-bone healing. METHODS: We assessed the histologic characteristics of the tendon-to-bone healing using the rabbit rotator cuff repair model. We divided the shoulders into 3 groups: control (without OCP/Gel composite), OCP/Gel composite (OCP+group), and Gel alone without OCP (Gel group) to evaluate the effectiveness of gelatin. RESULTS: Both the number of newly formed tendon fibers and the Sharpey fibers at the repair site increased in the OCP+group compared with those in the other 2 groups on hematoxylin-eosin staining (P < .05). On immunohistochemical evaluation, both the bone and the fibers in the OCP+group demonstrated that type I collagen was picked up, whereas the newly formed tendon fibers and Sharpey fibers revealed type III collagen. CONCLUSION: Treatment with OCP made collagen fibers and the Sharpey fibers, constituted by type I and type III collagens, increase at the tendon-to-bone insertion. It might be beneficial for the healing of rotator cuff tendon to bone.