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Bone Formation by Intramembranous Ossification01:29

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Intramembranous ossification is one of the two processes involved in the development of bones within an embryo. The flat bones of the face, most of the cranial bones, and the clavicles are formed via this process. During intramembranous ossification, the bones develop directly from sheets of undifferentiated mesenchymal connective tissue.
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Ring-opening metathesis polymerization or ROMP involves strained cycloalkenes as starting materials. The mechanism of ROMP proceeds by reacting cycloalkene with Grubbs catalyst to give metallacyclobutane intermediate which undergoes a ring-opening reaction to form new carbene. The new carbene reacts with another molecule of cycloalkene. Repetition of these steps leads to the formation of an unsaturated open-chain polymer product. All these steps are reversible, however, relieving the ring...
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Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶  nucleation, elongation, and steady-state phase.
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Formation of Species01:31

Formation of Species

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Speciation describes the formation of one or more new species from one or sometimes multiple original species. The resulting species are discrete from the parent species, and barriers to reproduction will typically exist. There are two primary mechanisms, speciation with and without geographic isolation—allopatric and sympatric speciation, respectively.
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There is no one solvent that can dissolve every type of solute. Some substances that readily dissolve in a certain solvent might be insoluble in a different solvent. A simple way to predict which substances dissolve in which solvent is the phrase "like dissolves like". This means that polar substances, such as salt and sugar, dissolve in a polar substance like water. In contrast, non-polar substances are more soluble in non-polar solvents such as carbon tetrachloride.
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Biodegradable polymerized simvastatin stimulates bone formation.

Nandakumar Venkatesan1, A D Thilanga Liyanage1, Jaime Castro-Núñez2

  • 1F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, USA.

Acta Biomaterialia
|May 6, 2019
PubMed
Summary
This summary is machine-generated.

Polymerized simvastatin (polysimvastatin) demonstrated significant new bone growth in a rat model, unlike traditional poly(lactic-co-glycolic acid) (PLGA) delivery systems which caused bone loss. Polysimvastatin shows promise for bone regeneration applications.

Keywords:
Controlled releaseDegradable biomaterialsOsteogenesisProdrugsSimvastatin

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Polymer Chemistry

Background:

  • Traditional poly(lactic-co-glycolic acid) (PLGA) drug delivery systems have limitations in drug payload and passive release.
  • Simvastatin, a drug with multiple physiological effects, can be polymerized into macromolecules (polysimvastatin) for enhanced delivery.
  • Previous in vitro studies demonstrated controlled simvastatin release from polymerized forms.

Purpose of the Study:

  • To evaluate the degradation and intramembranous bone-forming potential of simvastatin-containing polyprodrugs in vivo.
  • To compare the efficacy of poly(ethylene glycol)-block-poly(simvastatin) and its copolymers against conventional simvastatin-loaded PLGA.

Main Methods:

  • A rat calvarial onlay model was used to assess bone regeneration.
  • Poly(ethylene glycol)-block-poly(simvastatin) and poly(ethylene glycol)-block-poly(simvastatin)-ran-poly(glycolide) were compared with simvastatin-loaded PLGA and pure PLGA.
  • Degradation rates, bone formation, and gene expression (osteogenic, angiogenic, inflammatory) were analyzed.

Main Results:

  • Simvastatin polyprodrugs exhibited slower degradation compared to PLGA formulations.
  • Significant new bone growth was observed around poly(ethylene glycol)-block-poly(simvastatin) disks by 4 weeks.
  • PLGA loaded with simvastatin resulted in severe bone resorption and loss at 4 and 8 weeks, respectively.
  • No significant systemic effects on cholesterol or body weight were noted.
  • Increased expression of osteogenic, angiogenic, and inflammatory genes was observed for all polymers at 8 weeks.

Conclusions:

  • Poly(ethylene glycol)-block-poly(simvastatin) demonstrates slow degradation and controlled drug release, effectively controlling inflammation and promoting osteogenesis.
  • This polymer is a promising candidate for bone regeneration applications due to its integrated biofunctionality and degradability.
  • Polymerized simvastatin offers a superior alternative to conventional PLGA encapsulation for bone defect repair.