Critical size defect regeneration by rhPTH-collagen membrane as a new tissue engineering tool

Abstract

Recombinant Human Parathyroid Hormone (rhPTH 1-34) administration is an effective treatment to improve bone mass in osteoporosis. The aim of this study was to develop a Tissue Engeenering Tool for bone regeneration. We evaluated the efficacy of a freeze dried rhPTH membrane in calvarial critical size defect (CSD). Forty-four Wistar female rats (body weight 150 ± 50 g) with CSD (5 mm) were divided into four groups: group 1: rhPTH membrane (rhPTHm); group 2: atelocollagen membrane (Cm); group 3: rhPTH and atelocollagen I (CrhPTHm); group 4: without any treatment (CG). All samples were evaluated on the 1st, 3rd, and 6th weeks (weeks) post-surgery by soft X-ray, histological and histometric studies. Soft X-ray results showed a radiolucent image with many irregular radiopaque areas. Histologically, rhPTHm was replaced by reticular bone (7%) since 3rd week, and lamellar bone ossicles (30%) at 6th week. Cm showed bone formation like composite bone type on week 1st, 3rd, and 6th (2%, 44%, and 41%, respectively). With CrhPTHm, bone formation was observed in all periods (2.4%, 48%, and 53%), showing statistical difference with CG in the 3rd and 6th wks (p = 0.03 and 0.01). Our results demonstrated the effectiveness of a new biomaterial called CrhPTHm because its ability to regenerate calvarial CSD. Moreover, the membrane represents a new local intermittent delivery system allowing rhPTH slow release.

Bone Regeneration Induced by Local Delivery of a Modified PTH-Derived Peptide from Nanohydroxyapatite/Chitosan Coated True Bone Ceramics

“…With PTHdP loaded on implants, the PTHdP-10/CH/TBC and PTHdP-100/CH/TBC groups both revealed a remarkably stronger ability to stimulate peri-implant new bone formation and induce guided bone regeneration into implants interspace for the implantation periods used. These results were consistent with previous studies, which demonstrated enhanced osseointegration and bone-defect regeneration was obtained by local application of PTH. ,, In the present study, as PTHdP/CH/TBC implants were applied in vivo, the local concentration of released PTHdP for the first few days could be conceivably high because of the initial uncontrolled and rapid PTHdP release. As observed in vitro, this rapid release resulted in significant inhibitory effects on osteogenesis actions for MC3T3-E1 cell culture.…”

“…Generally, prolonged and high doses of exposure to PTH(1–34) leads to increased bone resorption, yet intermittent doses of higher amounts or infusion of low doses results in bone formation . In addition to its prevalent application in treating osteoporosis, intermittent administration of PTH(1–34) has been found to significantly stimulate bone-defect regeneration, , making it available to expand the application of PTH(1–34) to a bone graft procedure. , However, the inconvenience of daily injection, low bioavailability with short lasting duration, and even potential safety risk of systemic exposure severely hinder the broader application of PTH(1–34). , To overcome these disadvantages, localized and controlled delivery of PTH(1–34) via high-affinity immobilization on drug-delivery vehicles, such as PLGA microspheres, fibrin polymer, biomimetic CaP coating, polyethylene glycol-based matrix, and atelocollagen membrane, have been explored. As these studies concluded, a proper local delivery system could be effective to maintain the bioactivity of PTH(1–34) and achieve local bone healing without the potential problems caused by systemic PTH exposure.…”

A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

“…A recent report demonstrated that BMP2 plays an important role in host dura mater stimulation of human ASC osteogenesis in the context of calvarial bone healing [37]. Implant of recombinant human parathyroid hormone and atelocollagen I effectively regenerated critical-size Wistar female rat calvarial defects compared to use of atelocollagen I alone [38]. …”

Effect of bioactive glass particles on osteogenic differentiation of adipose‐derived mesenchymal stem cells seeded on lactide and caprolactone based scaffolds

“…1,2 Accordingly, metallic, ceramic, or polymeric scaffolds, alone or in combination with cells, can be satisfactorily employed to promote bone regeneration and facilitate the reconstruction of critical size defects. [3][4][5][6][7][8] Ideally, the scaffolds used for bone tissue engineering should have a three-dimensional, highly porous structure with an interconnected pore network. All these geometrical features facilitate cell migration and tissue ingrowth and are important for neovascularization, affecting directly the flow of nutrients and metabolic waste.…”

“…Considering the drawbacks associated to autografts and allograft for bone regeneration, such as scarcity of healthy tissue or possible rejection of the implanted grafts, tissue engineering is presented as a promising alternative for the reconstruction of critical size bone defects . Accordingly, metallic, ceramic, or polymeric scaffolds, alone or in combination with cells, can be satisfactorily employed to promote bone regeneration and facilitate the reconstruction of critical size defects …”