Biphasic Fusion of the Murine Posterior Frontal Suture

Hermann, Christopher D.; Richards, M.A.; CHANG, R. JEFFREY; Olivares-Navarrete, René; Williams, Joseph K.; Guldberg, Robert E.; Vidaković, Brani; Schwartz, Zvi; Boyan, Barbara D.

doi:10.1097/prs.0b013e3182827585

Cited by 7 publications

(4 citation statements)

References 30 publications

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“…These defects healed via a biphasic process in which they were first bridged with a discontinuous shell of bone on the endocranial surface of the skull, followed by a robust mineralization of the defect by two weeks following surgery. This is similar to fusion of the normal posterior frontal suture, which also first closes along the endocranial surface of the suture and is followed later by a mineralization phase [26]. …”

Section: Discussionmentioning

confidence: 93%

“…Moreover, defects not associated with the cranial suture will fail to heal with bone in weanling mice. Two time points were selected based on our previous work showing that at weaning (21 days post-natal), the posterior frontal suture in C57Bl/6J mice had fused but not mineralized whereas in adolescent mice (50 days post-natal) the posterior frontal suture has completed fusion and mineralization, but these mice have not reached sexual maturity [26]. Defect healing was assessed using image processing algorithms developed and validated previously [27].…”

Section: Introductionmentioning

confidence: 99%

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Rapid re-synostosis following suturectomy in pediatric mice is age and location dependent

Hermann

Lawrence

Olivares-Navarrete

et al. 2013

Bone

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Craniosynostosis is the premature fusion of the cranial sutures early in development. If left untreated, craniosynostosis can lead to complications resulting from cranial deformities or increased intracranial pressure. The standard treatment involves calvarial reconstruction, which in many cases undergoes rapid re-synostosis. This requires additional surgical intervention that is associated with a high incidence of life threatening complications. To better understand this rapid healing, a pediatric mouse model of re-synostosis was developed and characterized. Defects (1.5 mm by 2.5 mm) over the posterior frontal suture were created surgically in weanling (21 days post-natal) and adolescent (50 days post-natal) C57Bl/6J mice. In addition, defects were created in the frontal bone lateral to the posterior frontal suture. The regeneration of bone in the defect was assessed using advanced image processing algorithms on micro-computed tomography scans. The genes associated with defect healing were assessed by real-time PCR of mRNA isolated from the tissue present in the defect. The results showed that the weanling mouse healed in a biphasic process with bone bridging the defect by post-operative (post-op) day 3 followed by an increase in the bone volume on day 14. In adolescent mice, there was a delay in bone bridging across the defect, and no subsequent increase in bone volume. No bridging of the defect by 14 days post-op was seen in identically sized defects placed lateral to the suture in both a weanling and adolescent animals. This study demonstrates that bone regeneration in the cranium is both age and location dependent. Rapid and robust bone regeneration only occurred when the defect was created over the posterior frontal suture in immature weanling mice.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Rapid re-synostosis following suturectomy in pediatric mice is age and location dependent

Hermann

Lawrence

Olivares-Navarrete

et al. 2013

Bone

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“…We previously observed that bone formation in this model occurred after day 7 based on microCT and was correlated with a shift in expression of chondrogenic genes to osteogenic genes. 10,12 This suggests that osteogenesis within the defect was reduced because of the reduced vascularity.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of angiogenesis impairs bone healing in an in vivo murine rapid resynostosis model

Hyzy

Kajan

Wilson

et al. 2017

J Biomedical Materials Res

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Biologics can improve bone formation, but may diffuse away from sites of therapeutic need. We developed a click-chemistry hydrogel that rapidly polymerizes in situ to control delivery of biologics during post-suturectomy resynostosis in 21-day-old male mice. Here, we used this model to determine the role of angiogenesis in post-suturectomy resynostosis and examine whether controlled release of angiogenesis inhibitors could delay bone regeneration. Hydrogels [DB-co-PEG/poly (TEGDMA)-co-(N3-TEGDMA)] were produced containing anti-angiogenic compounds [anti-VEGFA-antibody or hypoxia inducible factor 1α-inhibitor topotecan]. Bioactivity in vitro was assessed by tube length and branching points of endothelial cells in hydrogel-conditioned media. In vivo effects were examined 14 day post-suturectomy, based on the temporal analysis of angiogenic mRNAs during resynostosis following posterior frontal suture removal. MicroCT was used to quantify angiogenesis in contrast-agent-perfused blood vessels and bone defect size in defects receiving hydrogel, anti-VEGFA/hydrogel, or topotecan/hydrogel. Shorter endothelial tube length and less branching were seen in inhibitor-conditioned media (topotecan > AbVEGFA). In vivo, both compounds inhibited angiogenesis compared with hydrogel-only. Anti-VEGFA/hydrogel reduced resynostosis compared with empty defects, but topotecan/hydrogel blocked bone regeneration. We demonstrate that anti-angiogenic compounds can be incorporated into a spontaneously polymerizing hydrogel and remain active over 14 days in vitro and in vivo. Moreover, bone formation can be delayed by inhibiting neovascularization, suggesting possible use as a therapeutic to control resynostosis following suturectomies and potential applications in other conditions where rapid osteogenesis is not desired. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2742-2749, 2017.

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“…*P < 0.05 vs. day 9; # P < 0.05 vs. day 12; $ P < 0.05 vs. day 20. Adapted fromHermann, Richards, et al (2013).…”

mentioning

confidence: 99%

Craniosynostosis and Resynostosis

et al. 2016

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Craniosynostosis occurs in approximately 1 in 2,000 children and results from the premature fusion of ≥1 cranial sutures. If left untreated, craniosynostosis can cause numerous complications as related to an increase in intracranial pressure or as a direct result from cranial deformities, or both. More than 100 known mutations may cause syndromic craniosynostosis, but the majority of cases are nonsyndromic, occurring as isolated defects. Most cases of craniosynostosis require complex cranial vault reconstruction that is associated with a high risk of morbidity. While the first operation typically has few complications, bone rapidly regrows in up to 40% of children who undergo it. This resynostosis typically requires additional surgical intervention, which can be associated with a high incidence of life-threatening complications. This article reviews work related to the dental and maxillofacial implications of craniosynostosis and discusses clinically relevant animal models related to craniosynostosis and resynostosis. In addition, information is provided on the imaging modalities used to study cranial defects in animals and humans.

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Biphasic Fusion of the Murine Posterior Frontal Suture

Cited by 7 publications

References 30 publications

Rapid re-synostosis following suturectomy in pediatric mice is age and location dependent

Rapid re-synostosis following suturectomy in pediatric mice is age and location dependent

Inhibition of angiogenesis impairs bone healing in an in vivo murine rapid resynostosis model

Craniosynostosis and Resynostosis

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