Perspectives on the clinical utility of allografts for bone regeneration within osseous defects: a narrative review

Abstract Background Distraction osteogenesis (DO) is a highly efficacious form of reconstructive bone regeneration, but its clinical utility is limited by the prolonged period required for bone consolidation to occur. Understanding the mechanistic basis for DO and shortening this consolidation phase thus represent promising approaches to improving the clinical utility of this procedure. Methods A mandibular DO (MDO) canine model was established, after which small RNA sequencing was performed to identify relevant molecular targets genes. Putative miRNA target genes were identified through bioinformatics and confirmed through qPCR, Western blotting, and dual-luciferase reporter assays. Peripheral blood samples were collected to isolate serum and endothelial colony-forming cells (ECFCs) in order to measure miR-205, NOTCH2, and angiogenic cytokines expression levels. Lentiviral constructs were then used to inhibit or overexpress miR-205 and NOTCH2 in isolated ECFCs, after which the angiogenic activity of these cells was evaluated in migration, wound healing, proliferation, tube formation, and chick chorioallantoic membrane (CAM) assay. Autologous ECFCs transfected to knockdown miR-205 and were injected directly into the distraction callus. On days 14, 28, 35 and 42 after surgery, bone density was evaluated via CBCT, and callus samples were collected and evaluated via histological staining to analyze bone regeneration and remodeling. Results MiR-205 was identified as being one of the miRNAs that was most significantly downregulated in MDO callus samples. Downregulation of miR-205 was also observed in DO-ECFCs and serum of animals undergoing MDO. Inhibiting miR-205 markedly enhanced angiogenesis, whereas overexpressing miR-205 had the opposite effect in vitro. Importantly, NOTCH2, which is a unique regulator in bone angiogenesis, was identified as a miR-205 target gene. Consistent with this regulatory relationship, knocking down NOTCH2 suppressed angiogenesis, and transduction with a miR-205 inhibitor lentivirus was sufficient to rescue angiogenic activity. When ECFCs in which miR-205 had been inhibited were transplanted into the MDO callus, this significantly bolstered osteogenesis, and remodeling in vivo. Conclusions MiR-205 is a significant regulator of the MDO process, and inhibiting this miRNA can accelerate MDO-related mineralization. Overall, these results offer new insights into the mechanistic basis for this procedure, highlighting potential targets for therapeutic clinical intervention.

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Utility of biomarkers in traumatic brain injury: a narrative review

Colombian Journal of Anesthesiology ◽

10.1097/cj9.0000000000000165 ◽

2020 ◽

Vol 48 (3) ◽

pp. 155-161

Author(s):

Daniel A. Mendoza ◽

Karen D. López ◽

Raúl A. Echeverri ◽

Laura Pastor ◽

Steven Rueda ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Clinical Utility ◽

Diagnostic Techniques ◽

Narrative Review ◽

Diagnostic Methods ◽

Neurological Injury ◽

The Past ◽

Molecular Events

Introduction: With the evolution of diagnostic techniques in traumatic brain injury (TBI), the study of neurological injury has made progress based on the concepts of primary and secondary injury, leading to the era of proteomics to understand the complex molecular events involved in the process. Objectives: This narrative review is intended to discuss the state of the art of the most frequently used biomarkers in TBI, their clinical utility, and the implications for therapeutic decisionmaking protocols. Materials and methods: In order to fulfill the objective of this paper, a literature review was conducted of the most important databases. Results: Several biomarkers have been studied as prognostic factors in patients with TBI. Learning about their sensitivity and specificity in neurological injury, and its post-trauma evolution over time, has been the goal of various papers in the past few years. Conclusion: Breakthroughs in the study of protein degradation make it necessary to broaden the spectrumand knowledge of new diagnostic methods in TBI. Further studies are needed to define the role of biomarkers and to promote protocols integrating specific values.

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A Combination of Biphasic Calcium Phosphate (Maxresorb®) and Hyaluronic Acid Gel (Hyadent®) for Repairing Osseous Defects in a Rat Model

Applied Sciences ◽

10.3390/app10051651 ◽

2020 ◽

Vol 10 (5) ◽

pp. 1651 ◽

Cited By ~ 3

Author(s):

Abeer G. Ahmed ◽

Fatin A. Awartani ◽

Abdurahman A. Niazy ◽

John A. Jansen ◽

Hamdan S. Alghamdi

Keyword(s):

Hyaluronic Acid ◽

Calcium Phosphate ◽

Bone Regeneration ◽

Rat Model ◽

Biphasic Calcium Phosphate ◽

Bone Defects ◽

Group I ◽

Male Wistar Rats ◽

Osseous Defects

The aim of this in vivo study was to evaluate the efficacy of biphasic calcium phosphate (Maxresorb®, BCP) used in combination with hyaluronic acid (Hyadent®, HyA) gel for regeneration of osseous defects in a rat model. Bilateral femoral condylar bone defects (3 mm diameter and 3 mm depth) were created in 40 male Wistar rats. The defects were grafted as group I (BCP only), group II (BCP + HyA), group III (HyA only), and group IV (empty control). At four weeks and 10 weeks, the bone specimens were evaluated using histological and histomorphometrical analyses to identify the newly formed bone area (NF-BA (%)), as well as the remaining BCP particles (R-BCP (%)). Light microscopic examination indicated the absence of an inflammatory reaction within the bone defects after four weeks or 10 weeks of implantation. Significant new bone regeneration was present in the bone defects grafted with BCP or BCP + HyA biomaterials, as early as four weeks, compared to control groups. The addition of HyA to BCP did not significantly improve bone regeneration at four weeks or 10 weeks. Nevertheless, its role in bone healing and regeneration warrants further investigation.

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