A Follow-Up Study on the Clinical Outcomes of Alveolar Reconstruction Using Octacalcium Phosphate Granules and Atelocollagen Complex.

PURPOSE: To observe the long-term postoperative bone formation and eruption of adjacent teeth after octacalcium phosphate granule and atelocollagen complex (OCP/Col) grafting in the treatment of alveolar cleft of patients with unilateral cleft lip with or without cleft palate (UCL ± P). METHODS: Four patients with UCL ± P who underwent OCP/Col grafting (OCP group), and 55 patients with UCL ± P who underwent autologous bone grafting (AB group) were enrolled in this study. OCP/Col or autologous bone grafting was performed before the eruption of canines or lateral incisors in mixed dentition, followed by orthodontic management. Patients in the OCP group underwent radiography before and after surgery at 1, 2, 3, 6, and over 30 months postoperatively. The volume and area of the bony defect in the alveolar cleft area were compared between the OCP and AB groups before and after 6 months of surgery. RESULTS: The bone bridge in all patients in the OCP/Col group was successfully formed, and by 6 months postoperatively, the permanent teeth adjacent to the alveolar cleft had erupted at the site of the OCP/Col complex graft. Comparison of the pre- and postoperative bone defects between the 2 groups revealed almost the same extent of bone bridge formation. CONCLUSIONS: OCP/Col grafting could be considered as an alternative to autologous bone grafting as it yielded successful bone bridge formation and facilitated permanent tooth eruption.

Bone regeneration by freeze-dried composite of octacalcium phosphate collagen and teriparatide.

OBJECTIVE: Octacalcium phosphate (OCP) and collagen (col) composite (OCPcol) demonstrated superior bone regeneration properties, and its commercialization appears to be forthcoming. As a practical medical material for new combination products, we developed a freeze-dried composite with OCPcol and teriparatide (TPTD) (OCPcolTPTDf), and investigated its bone regenerative properties. MATERIALS AND METHODS: A disk of OCPcol was made by mixing OCP granules and atelocollagen for medical use. Then, OCPcolTPTDf was prepared by impregnation of the OCPcol disk with 1.0 or 0.1 µg of TPTD solution (OCPcolTPTDf 1.0 and OCPcolTPTDf 0.1, respectively) followed by lyophilization. In vitro release profiles of TPTD from OCPcolTPTDf were determined using an enzyme-linked immunosorbent assay. Implantation of OCPcolTPTDf or OCPcol was carried out for a rat critical-sized calvarial defect. And five defects in each group were collected after 12 weeks of implantation. RESULTS: The retention-release profiles of TPTD from OCPcolTPTDf supported a higher degree of retention of TPTD. Radiographic, histological, and histomorphometric examinations indicated that regenerated bone was filled in most of the defects of the OCPcolTPTDf. Additionally, the OCPcolTPTDf groups showed significantly enhanced bone regeneration compared with the OCPcol group. CONCLUSIONS: These results suggested that this newly developed bone regenerative composite could be a practical medical material.

The regenerated bone quality by implantation of octacalcium phosphate collagen composites in a canine alveolar cleft model.

OBJECTIVE: Synthetic octacalcium phosphate and porcine atelocollagen composites significantly enhanced bone regeneration more than ß-tricalcium phosphate collagen composite and hydroxyapatite collagen composite in a rat cranial defect model. However, the long-term stability and quality of octacalcium phosphate collagen (OCP/Col) composites-derived regenerated bone, when implanted in a canine alveolar cleft model, have yet to be elucidated. The present study investigated the longterm stability and quality of bone regenerated by OCP/Col. DESIGN: Disks of OCP/Col or collagen were implanted in a canine alveolar-cleft model (n = 6). Then, bone regeneration in the implanted areas was investigated macroscopically, radiographically, and histologically at 10 months after implantation. In addition, three-dimensional quantitative images of regenerated bone were analyzed by microcomputed tomography. RESULTS: Macroscopically, the OCP/Col treated alveolus was clearly augmented, and radio-opacity in the OCP/Col implanted area was comparable to that of the original alveolus bone. On histological analysis, the area was mostly filled with newly formed bone, and a few granules of implanted OCP/Col were enclosed in it. In the microcomputed tomography analysis, the regenerated bone volume in the OCP/Col group was larger than that in the collagen group. OCP/Col-derived bone consisted of outer cortical and inner cancellous structure with dense trabeculae and seemed like the original bone structure. CONCLUSIONS: OCP/Co composites could be a useful bone regenerative material to substitute for autogenous bone because their implantation could elicit high bone regeneration and active structural reconstitution.

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.

Long-term clinical and radiographic evaluation after maxillary sinus floor augmentation with octacalcium phosphate-collagen composite: A retrospective case series study.

The purpose of this study was to evaluate, using clinical and radiological assessments, the stability of dental implants 5 years after maxillary sinus floor augmentation with octacalcium phosphate-collagen composite (OCP/Col). Maxillary sinus floor augmentation was performed through a lateral window approach. Depending on the height of the host bone, a simultaneous approach (≥5 mm) or a staged approach (less than 5 mm) was employed. The primary outcome was the evaluation of clinical dental implant conditions such as infection, peri-implantitis, dental implant stability, pain, and paresthesia. Secondary outcomes were the evaluation of the augmented bone volume, change rate of augmented bone volume, vertical bone height, and marginal bone loss around dental implant fixture. The conditions of all dental implants were uneventful throughout the follow-up period. Augmented bone volume and changing rate of augmented bone volume were essentially unchanged following maturation of the OCP/Col-derived new bone. The change rate of new bone volume was 21.9% in the simulated approach and 16.8% in the staged approach at 1 year and 5 years postoperatively. The reduction rate in vertical bone height was 7.1% in the simultaneous approach and 7.5% in the staged approach between 1 year and 5 years postoperatively. Mean marginal bone loss was 1.76 mm with the simultaneous approach, and 0.50 mm with the staged approach at 5 years postoperatively. In conclusion, the success of dental implants 5 years after sinus floor augmentation by OCP/Col implantation was clarified by both clinical and radiological evaluations.

Proteome analysis of rat serum proteins adsorbed onto synthetic octacalcium phosphate crystals.

The present study was designed to determine which proteins are selectively adsorbed onto two bone substitute materials, octacalcium phosphate (OCP) and hydroxyapatite (HA) crystals, from rat serum by proteome analysis. Ground crystals of synthetic OCP and commercially available sintered HA, with the same surface area, were incubated in rat serum proteins at 37°C for 24 h. The proteins from the crystals extracted with guanidine-HCl-EDTA were listed on the basis of the results of liquid chromatography tandem mass spectrometry (LC/MS/MS). A total of 138 proteins were detected from OCP; 103 proteins were detected from HA. Forty-eight proteins were from both crystals. A quantitative analysis of the proteins detected was performed for the extracted two bone formation-related proteins apolipoprotein E (Apo E), a protein known to promote osteoblast differentiation, and complement 3 (C3). HA adsorbed C3 (3.98 ± 0.03 fmol/µg protein) more than OCP (1.81 ± 0.07 fmol/µg protein) did, while OCP adsorbed Apo E (2.42 ± 0.03 fmol/µg protein) more than HA (1.21 ± 0.01 fmol/µg protein) did even after deleting the high-abundance proteins, such as albumin. The results demonstrated that OCP exhibits a similar property but distinct capacity with HA in adsorbing bone formation-related proteins from the serum constituents.

The effect of synthetic octacalcium phosphate in a collagen scaffold on the osteogenicity of mesenchymal stem cells.

Although the efficacy of the in vivo osteogenic capabilities of synthetic octacalcium phosphate (OCP) crystal implantation can be explained through its stimulatory capacity for the differentiation of the host osteoblastic cell lineage, direct evidence that OCP supports bone regeneration by osteogenic cells in vivo has not been shown. Mesenchymal stem cells (MSCs) isolated from 4-week-old male Wistar rat long bones were pre-incubated in osteogenic or maintenance medium in the presence or absence of basic fibroblast growth factor (bFGF). OCP/Collagen (OCP/Col) or collagen disks were seeded with MSCs that had been pre-incubated in osteogenic medium containing bFGF, which exhibited the highest differentiation induction, and then incubated for an additional day. The disks were implanted in critical-sized calvaria defects of 12-week-old male Wistar rats and the specimens were analysed radiographically, histologically, histomorphometrically, and by micro-computed tomography (CT) imaging at 4 and 8 weeks after the implantation. The OCP/Col·MSCs group rapidly induced more bone regeneration, even within 4 weeks, compared to the OCP/Col group without MSCs. The bone mineral density of the OCP/Col·MSCs group was also greater than the OCP/Col group. The Col·MSCs group did not exhibit prominent osteogenicity. These results indicate that OCP crystals in a collagen matrix efficiently promote exogenously introduced osteogenic cells to initiate bone regeneration if the cells are pre-treated in a suitable differentiation condition.

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.

Bone augmentation by octacalcium phosphate and collagen composite coated with poly-lactic acid cage.

OBJECTIVE: Although octacalcium phosphate and collagen composite (OCP/Col) has demonstrated excellent bone regeneration, it has never achieved bone augmentation. The present study investigated whether it could be enabled by OCP/Col disks treated with parathyroid hormone (PTH) and covered with a poly-lactic acid (PLA) cage. MATERIALS AND METHODS: The prepared OCP/Col disks with three different types of PLA cages (no hole, one large hole, several small holes) were implanted into subperiosteal pockets in rodent calvaria. Histological, and histomorphometric analyses were conducted at 12 weeks after implantation. RESULTS: Implants with all PLA cage variants achieved sufficient bone augmentation, and analyses showed that new bone was formed from the original bone and along the PLA cage. While the PLA cage variant with no holes sporadically evoked new bone formation even at the central area of the roof of the PLA cage, the PLA cage variants with holes had no new bone in the area of the hole or beneath the periosteum. CONCLUSIONS: These results suggest that sufficient bone augmentation could be achieved by treating the OCP/Col disks with PTH and covering them with a PLA cage, and periosteum might not have been involved in the bone formation in this experiment.

Influence of pre-freezing conditions of octacalcium phosphate and collagen composite for reproducible appositional bone formation.

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.

First clinical application of octacalcium phosphate collagen composite on bone regeneration in maxillary sinus floor augmentation: A prospective, single-arm, open-label clinical trial.

The overall objective of this study was to assess the safety and efficacy of OCP/Col as a bone substitute material for bone regeneration during sinus floor augmentation. Maxillary sinus floor augmentation was performed thorough lateral window approach. According to the height of host bone, simultaneous approach (≥5 mm) or staged approach (less than 5 mm) was applied. In this research, clinical findings of dental implant treatment after setting the restorations were set as a primary endpoint in both approaches (infection, inflammation around the implant, movement of the implant, pain, sensory disorder, and bone resorption around the implant body on radiological evaluation.). In staged approach, histological evaluation of bone biopsy specimen was also conducted. As secondary endpoints, hounsfield unit (HU) value, vertical bone height, implant stability quotient (ISQ), and adverse events during the research were evaluated. In all cases, as a primary endpoint, clinical findings after setting the restorations were uneventful with no adverse events. Histological structure demonstrated mature bone derived from OCP/Col. In the ossified area, osteogenesis was observed around OCP granules, and osteoblast-like cells were arrayed around OCP granules. Osteocyte encapsulation was recognized in the new bone. HU increased over time with both approaches. Vertical bone height significantly increased at 3 months postoperatively, and maintained during follow-up. ISQ increased with both approaches. In particular, ISQ was significantly increased with the staged approach. This clinical trial demonstrated the safety and efficacy of OCP/Col for bone regeneration in maxillary sinus floor augmentation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:243-252, 2020.

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.

Octacalcium phosphate collagen composite (OCP/Col) enhance bone regeneration in a rat model of skull defect with dural defect.

Cranial bone defects are a major issue in the field of neurosurgery, and improper management of such defects can cause cosmetic issues as well as more serious infections and inflammation. Several strategies exist to manage these defects clinically, but most rely on synthetic materials that are prone to complications; thus, a bone regenerative approach would be superior. We tested a material (octacalcium phosphate collagen composite [OCP/Col]) that is known to enhance bone regeneration in a skull defect model in rats. Using a critical-sized rat skull defect model, OCP/Col was implanted in rats with an intact dura or with a partial defect of the dura. The results were compared with those in a no-treatment group over the course of 12 weeks using computed tomographic and histological analysis. OCP/Col enhanced bone regeneration, regardless of whether there was a defect of the dura. OCP/Col can be used to treat skull defects, even when the dura is injured or removed surgically, via bone regeneration with enhanced resorption of OCP/Col, thus limiting the risk of infection greatly.

Clinical study of octacalcium phosphate and collagen composite in oral and maxillofacial surgery.

Octacalcium phosphate and its collagen composite have been recognized as bone substitute materials possessing osteoconductivity and biodegradation properties. We evaluated the effectiveness of octacalcium phosphate and its collagen composite used for bone augmentation in major oral and maxillofacial surgeries in a clinical trial. Octacalcium phosphate and its collagen composite were used in cases of sinus floor elevation in 1- and 2-stage, socket preservation, cyst, and alveolar cleft procedures. A total of 60 patients were evaluated for effectiveness after the implantation of octacalcium phosphate and its collagen composite. Although sinus floor elevation in 1-stage, cyst, and alveolar cleft cases met the criteria for the judgment of success, sinus floor elevation in 2-stage and socket preservation groups did not meet the criteria in the initial evaluation. However, an additional evaluation for reconfirmation revealed the effectiveness of octacalcium phosphate and its collagen composite in those groups, and all evaluation results ultimately indicated the success of this clinical trial. Therefore, this clinical trial suggested that application of octacalcium phosphate and its collagen composite for oral and maxillofacial surgery was safe and effective and that octacalcium phosphate and its collagen composite could be a bone substitute candidate instead of autologous bone.

Single-dose local administration of teriparatide with a octacalcium phosphate collagen composite enhances bone regeneration in a rodent critical-sized calvarial defect.

Octacalcium phosphate and collagen composite (OCP/Col) achieves stable bone regeneration without cell transplantation in preclinical studies. Recently, a sponsor-initiated clinical trial was conducted to commercialize the material. The present study investigated bone regeneration by OCP/Col with the single local administration of teriparatide (parathyroid hormone 1-34; TPTD). OCP/Col was prepared by mixing sieved granules of OCP and atelocollagen for medical use and a disk was molded. After the creation of a rodent critical-sized calvarial defect, OCP/Col or OCP/Col with dripped TPTD solution (1.0 or 0.1 µg; OCP/Col/TPTDd1.0 or OCP/Col/TPTDd0.1) was implanted into the defect. Six defects in each group were fixed 12 weeks after implantation. Radiographic examinations indicated that radiopaque figures in defects treated with OCP/Col with TPTD (OCP/Col/TPTDd) occupied a wider range than those treated with OCP/Col. Histological results demonstrated that most of the defect in OCP/Col/TPTDd was filled with newly formed bone. A histomorphometrical examination indicated that the percentage of newly formed bone was significantly higher in the defects of OCP/Col/TPTDd 1.0 (53.6 ± 4.3%) and OCP/Col/TPTDd 0.1 (52.2 ± 7.4%) than in those of OCP/Col (40.1 ± 8.4%), whereas no significant differences were observed between OCP/Col/TPTDd1.0 and OCP/Col/TPTDd0.1. These results suggest that OCP/Col with the single local administration of TPTD enhances bone regeneration in a rodent calvarial critical-sized bone defect. © 2017 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1851-1857, 2018.

Influence of electron beam irradiation doses on bone regeneration by octacalcium phosphate collagen composites.

An octacalcium phosphate and collagen composite (OCP/Col) achieved efficient bone regeneration with excellent resorbability. After the confirmation of its safety and efficacy in preclinical animal studies, the present study investigated the influence of electron beam irradiation doses on bone regeneration by OCP/Col in order to secure its commercialization. OCP/Col was prepared as previously described and the packed OCP/Col was sterilized using different doses of electron beam irradiation. A standardized defect, 9 mm in diameter, was made in the rat calvarium. A disk of OCP/Col (diameter 9 mm, thickness 1.5 mm) sterilized using different doses of electron beam irradiation was then implanted into the defect. Five defects in each group were treated and fixed 4, 12 and 24 weeks after implantation. Specimens were decalcified and stained with haematoxylin and eosin. In a histomorphometrical analysis, the percentage of newly formed bone in the defect (n-Bone%) was calculated. In OCP/Col 15 kGy, newly formed bone was enhanced and present throughout the defect with the resorption of OCP/Col. Furthermore, vigorous bone remodelling and bone maturation were observed. In OCP/Col 40 kGy, newly formed bone was not as prominent as that with OCP/Col 15 kGy. A histomorphometrical analysis using Student's t-test at 24 weeks revealed that the n-Bone% of OCP/Col 15 kGy (65.9 ± 7.14%) was significantly higher than that of OCP/Col 40 kGy (38.0 ± 10.2%). These results suggest that different electron beam irradiation doses influence bone regeneration by OCP/Col.

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.

The primacy of octacalcium phosphate collagen composites in bone regeneration.

We have engineered a scaffold constructed of synthetic octacalcium phosphate (OCP) and porcine collagen sponge (OCP/Col), and reported that OCP/Col drastically enhanced bone regeneration. In this study, we investigated whether OCP/Col would enhance bone regeneration more than beta-tricalcium phosphate (beta-TCP) collagen composite (beta-TCP/Col) or hydroxyapatite (HA) collagen composite (HA/Col). Discs of OCP/Col, beta-TCP/Col, or HA/Col were implanted into critical-sized defects in rat crania and fixed at 4 or 12 weeks after implantation. The newly formed bone and the remaining granules of implants in the defect were determined by histomorphometrical analysis, and radiographic and histological examinations were performed. Statistical analysis showed that the newly formed bone by the implantation of OCP/Col was significantly more than that of beta-TCP/Col or HA/Col. In contrast, the remaining granules in OCP/Col were significantly lower than those in beta-TCP/Col or HA/Col. Bone regeneration by OCP/Col was based on secured calcified collagen and bone nucleation by OCP, whereas bone regeneration by beta-TCP/Col or HA/Col was initiated by poorly calcified collagen and osteoconductivity by beta-TCP or HA. This study showed that the implantation of OCP/Col in a rat cranial defect enhanced more bone regeneration than beta-TCP/Col and HA/Col.

Octacalcium phosphate collagen composite facilitates bone regeneration of large mandibular bone defect in humans.

Recently it was reported that the implantation of octacalcium phosphate (OCP) and collagen composite (OCP-collagen) was effective at promoting bone healing in small bone defects after cystectomy in humans. In addition, OCP-collagen promoted bone regeneration in a critical-sized bone defect of a rodent or canine model. In this study, OCP-collagen was implanted into a human mandibular bone defect with a longer axis of approximately 40 mm, which was diagnosed as a residual cyst with apical periodontitis. The amount of OCP-collagen implanted was about five times greater than the amounts implanted in previous clinical cases. Postoperative wound healing was satisfactory and no infection or allergic reactions occurred. The OCP-collagen-treated lesion was gradually filled with radio-opaque figures, and the alveolar region occupied the whole of the bone defect 12 months after implantation. This study suggests that OCP-collagen could be a useful bone substitute material for repairing large bone defects in humans that might not heal spontaneously. Copyright © 2015 John Wiley & Sons, Ltd.

Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite.

The present study was designed to investigate whether hydrolysis of synthetic octacalcium phosphate (OCP) into hydroxyapatite affects bone formation. Mouse bone marrow stromal ST-2 cells and primary calvarial osteoblastic cells were cultured on the dishes pre-coated with OCP or its hydrolyzed Ca-deficient hydroxyapatite (OCP hydrolyzate; HL). The capacity of proliferation and differentiation was determined up to day 20. Granules of OCP and HL were implanted into critical-size rat calvaria defects for 4 and 12 weeks, and then bone formation was measured by histomorphometry. Structural changes of incubated and implanted OCP were determined by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The proliferation of both ST-2 and primary osteoblasts cultured on OCP or HL was initially inhibited, whereas their differentiation to osteoblasts was promoted at last. Implantation of OCP in bone defect more significantly enhanced bone formation than that of HL until 12 weeks. OCP tended to convert to apatite in vitro and in vivo. The conversion of the implanted OCP was ascertained to advance gradually with implantation periods. Taken together, these results suggest that OCP supports appositional bone formation and OCP-apatite conversion may be involved in this stimulatory capacity of OCP.