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The effect of 4-hexylresorcinol on xenograft degradation in a rat calvarial defect model.

ABSTRACT: The objective of this study was to evaluate xenograft degradation velocity when treated with 4-hexylresorcinol (4HR).The scapula of a cow was purchased from a local grocery, and discs (diameter 8 mm, thickness 1 mm) were prepared by trephine bur. Discs treated with 4HR were used as the experimental group. Untreated discs were used as the control. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), antibacterial test, endotoxin test, and scanning electron microscopy (SEM) were performed on the discs. In vivo degradation was evaluated by the rat calvarial defect model.The XRD and FT-IR results demonstrated successful incorporation of 4HR into the bovine bone. The experimental disc showed antibacterial properties. The endotoxin test yielded results below the level of endotoxin contamination. In the SEM exam, the surface of the experimental group showed needle-shaped crystal and spreading of RAW264.7 cells. In the animal experiments, the amount of residual graft was significantly smaller in the experimental group compared to the control group (P?=?0.003).In this study, 4HR was successfully incorporated into bovine bone, and 4HR-incorporated bovine bone had antibacterial properties. In vivo experiments demonstrated that 4HR-incorporated bovine bone showed more rapid degradation than untreated bovine bone.

SUBMITTER: Kang YJ

PROVIDER: S-EPMC4974267 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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The effect of 4-hexylresorcinol on xenograft degradation in a rat calvarial defect model.

Kang Yei-Jin YJ Noh Ji-Eun JE Lee Myung-Jin MJ Chae Weon-Sik WS Lee Si Young SY Kim Seong-Gon SG

Maxillofacial plastic and reconstructive surgery 20160805 1

<h4>Background</h4>The objective of this study was to evaluate xenograft degradation velocity when treated with 4-hexylresorcinol (4HR).<h4>Methods</h4>The scapula of a cow was purchased from a local grocery, and discs (diameter 8 mm, thickness 1 mm) were prepared by trephine bur. Discs treated with 4HR were used as the experimental group. Untreated discs were used as the control. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), antibacterial test, endotoxin test, and sc ...[more]

PMID: 27547747

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Project description:BACKGROUND:Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth, short stature, clavicular dysplasia, and osteoporosis. At present, as a therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC) transplantation therapy is performed in addition to drug therapy. However, MSC-based therapy for osteoporosis in CCD patients is difficult due to a reduction in the ability of MSCs to differentiate into osteoblasts resulting from impaired RUNX2 function. Here, we investigated whether induced pluripotent stem cells (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2 mutation in iPSCs derived from CCD patients to establish normal iPSCs, and whether engraftment of osteoblasts derived from properly reverted iPSCs results in better regeneration in immunodeficient rat calvarial bone defect models. METHODS:Two cases of CCD patient-derived induced pluripotent stem cells (CCD-iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using programmable nucleases, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs. The mRNA expressions of osteoblast-specific markers were analyzed using quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived osteoblasts were transplanted into rat calvarial bone defects, and bone regeneration was evaluated using microcomputed tomography analysis and histological analysis. RESULTS:Mutation analysis showed that both contained nonsense mutations: one at the very beginning of exon 1 and the other at the initial position of the nuclear matrix-targeting signal. The osteoblasts derived from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast differentiation markers, and transplantation of these osteoblasts into calvarial bone defects created in rats with severe combined immunodeficiency showed poor regeneration. However, reverted iPSCs improved the abnormal osteoblast differentiation which resulted in much better engraftment into the rat calvarial bone defect. CONCLUSIONS:Taken together, these results demonstrate that patient-specific iPSC technology can not only provide a useful disease model to elucidate the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing prospect that reverted iPSCs might provide a practical medical treatment for CCD.

Project description:Self-fitting scaffolds prepared from biodegradable poly(ε-caprolactone)-diacrylate (PCL-DA) have been developed for the treatment of craniomaxillofacial (CMF) bone defects. As a thermoresponsive shape memory polymer (SMP), with the mere exposure to warm saline, these porous scaffolds achieve a conformal fit in defects. This behavior was expected to be advantageous to osseointegration and thus bone healing. Herein, for an initial assessment of their regenerative potential, a pilot in vivo study was performed using a rabbit calvarial defect model. Exogenous growth factors and cells were excluded from the scaffolds. Key scaffold material properties were confirmed to be maintained following gamma sterilization. To assess scaffold integration and neotissue infiltration along the defect perimeter, non-critically sized (d = 8 mm) bilateral calvarial defects were created in 12 New Zealand white rabbits. Bone formation was assessed at 4 and 16 weeks using histological analysis and micro-CT, comparing defects treated with an SMP scaffold (d = 9 mm x t = 1 or 2 mm) to untreated defects (i.e. defects able to heal without intervention). To further assess osseointegration, push-out tests were performed at 16 weeks and compared to defects treated with poly(ether ether ketone) (PEEK) discs (d = 8.5 mm x t = 2 mm). The results of this study confirmed that the SMP scaffolds were biocompatible and highly conducive to bone formation and ingrowth at the perimeter. Ultimately, this resulted in similar bone volume and surface area versus untreated defects and superior performance in push-out testing versus defects treated with PEEK discs. STATEMENT OF SIGNIFICANCE: Current treatments of craniomaxillofacial (CMF) bone defects include biologic and synthetic grafts but they are limited in their ability to form good contact with adjacent tissue. A regenerative engineering approach using a biologic-free scaffold able to achieve conformal fitting represents a potential "off-the-shelf" surgical product to heal CMF bone defects. Having not yet been evaluated in vivo, this study provided the preliminary assessment of the bone healing potential of self-fitting PCL scaffolds using a rabbit calvarial defect model. The study was designed to assess scaffold biocompatibility as well as bone formation and ingrowth using histology, micro-CT, and biomechanical push-out tests. The favorable results provide a basis to pursue establishing self-fitting scaffolds as a treatment option for CMF defects.

Dataset Information

The effect of 4-hexylresorcinol on xenograft degradation in a rat calvarial defect model.

Publications

The effect of 4-hexylresorcinol on xenograft degradation in a rat calvarial defect model.

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