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

Abstract

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.

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

“…The procedure for the implantation of OCP/Col and β‐TCP/Col disks has been previously described (Iwai et al, ; Kamakura et al, ). The experimental animals were anesthetized intraperitoneally with 0.15 mg/kg dexmedetomidine hydrochloride (Domitor) (Nippon Zenyaku Kogyo Co., Ltd., Koriyama, Fukushima, Japan), 2.5 mg/kg butorphanol tartrate (Vetorphale) (Meiji Seika Pharma Co., Tokyo, Japan), and 2 mg/kg midazolam (Dormicum) (Astellas Pharma, Tokyo, Japan).…”

The role of bone anabolic drugs in the management of periodontitis: a scoping review

“…Teriparatide may enhance periodontal healing as demonstrated by higher number of PCNA-and VEGF-positive cells, and increased osterix expression, thus promoting PDL cell proliferation, angiogenesis, and osteoblast differentiation (Yoshida et al, 2019). Even local delivery thorough disks containing teriparatide solution seems to have similar effects, suggesting that this route of administration is effective while reducing the risk of potential systemic side effects (Iwai et al, 2018;Kajii et al, 2018). However, it should be highlighted that dosing regimens of teriparatide used in animal studies are quite heterogeneous.…”

“…Considering local application of teriparatide (1.0 or 0.1 µg), Kajii et al (2018) found that local drip of this drug into rat calvarial defects treated with OCP and collagen composite, led to a significantly higher percentage of newly formed bone, independently from teriparatide dosage. Similarly, Iwai et al (2018) showed that adding teriparatide (1.0 or 0.1 µg) in disks composed by OCP or β-TCP with collagen, significantly enhanced bone healing of critical size defects in rat calvaria. Marques et al (2009) investigated the effects of systemic intermittent administration of teriparatide (40 µg/kg daily) on periodontal tissues in rats with ligature-induced experimental periodontitis.…”

“…Teriparatide Animal Local 18 (6 × 3 groups) The addition of teriparatide solution (1.0 or 0.1 µg) on OCP/collagen disk implanted in 9 mm calvarial rat defects significantly improved bone regeneration, showing better results than OCP/collagen alone both at the μCT and at the histological analysis. Iwai et al, 2018 Teriparatide Animal Local 30 (5 × 6 groups) The addition of teriparatide (1.0 or 0.1 µg) in disks composed by OCP or β-TCP and collagen significantly improved new bone formation in 9 mm diameter rat calvarial defects.…”

Segmental Bone Reconstruction by Octacalcium Phosphate Collagen Composites with Teriparatide

“… 28 , 29 Recently, it was reported that OCPcol with a local single administration of TPTD (1 or 0.1 μg), which is a relatively low dose similar to that for the treatment for osteoporosis, enhanced bone repair of a critical-sized bone defect. 30 , 31 Hence, the present study investigated whether single-dose local administration of TPTD with OCPcol achieved bone reconstruction if implanted into a canine segmental mandibular bone defect.…”