Osteoclast modulatory biomaterials for skull regeneration

用于颅骨再生的破骨细胞调节生物材料

基本信息

  • 批准号:
    10451692
  • 负责人:
  • 金额:
    $ 36.86万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Skull defects occur secondary to trauma, stroke, cancer, and congenital anomalies resulting in significant neurological, psychological, social, and vocational burdens. Current clinical options for cranioplasty, or calvarial reconstruction, are limited by availability and morbidity in autologous bone grafts and complications and cost in alloplastic materials. Such drawbacks provide an opportunity to develop methods that specifically target calvarial bone regeneration. Despite decades of research, contemporary regenerative strategies consisting of expanded stem cells and growth factor cocktails delivered by scaffolding materials have not attained clinical translation due to surgical impracticality, cost, time consumption, and safety concerns. The increasing knowledge of instructive capabilities of the extracellular matrix (ECM) in cell fate determination has provided an alternative paradigm for regeneration. We demonstrated that an ECM-inspired material composed of nanoparticulate mineralized collagen glycosaminoglycan (MC-GAG) regenerates up to 60% the mineralization and biomechanical properties of native calvarium without ex vivo progenitor cell loading or exogenous growth factor supplementation. Simultaneously, MC-GAG inhibits osteoclast activation and resorption without affecting the paracrine osteoinductive properties offered by osteoclasts via direct material to cell interactions as well as indirectly by inducing osteoprogenitors to secrete osteoprotegerin (OPG), an endogenous inhibitor for osteoclast activation. With the addition of exogenous OPG, this uncoupling of osteogenesis from osteoclastogenesis is augmented. In combination, these data provided a proof of principle that a composite material of MC-GAG and OPG (MCGO) delivered in a temporospatially-limited manner may be a potential material for calvarial regeneration. In order to develop the MCGO material for clinical translation, three questions must be answered: 1. What are the mechanisms activated in osteoclasts by direct interactions with MC-GAG? 2. As the resorptive abilities of osteoclasts are necessary for remodeling and maturation of bone, how long should OPG exist in the system? 3. Should OPG be eluted or anchored to the material? To answer these questions, we have developed two MCGO materials via non-covalent and covalent incorporation of OPG resulting in a high concentration, fast release and a low concentration, extended release MCGO material, respectively. In Aim 1, we will elucidate the anti-osteoclastogenic mechanisms induced by MC-GAG and MCGO materials. We hypothesize that MC-GAG and the two MCGO materials will differentially affect hOC activation and resorption. In Aim 2, we will evaluate the two MCGO materials compared to MC-GAG in rabbit calvarial regeneration to generate preclinical efficacy, safety, and performance data for MCGO materials compared to MC-GAG. Our proposed studies are unified in the goal of calvarial regenerative technology development. At the conclusion of the proposed studies, we expect to have amassed significant preclinical data to support an IDE application for MCGO materials to the FDA.
项目总结/文摘

项目成果

期刊论文数量(0)
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Justine Chia Lee其他文献

Justine Chia Lee的其他文献

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{{ truncateString('Justine Chia Lee', 18)}}的其他基金

Osteoclast modulatory biomaterials for skull regeneration
用于颅骨再生的破骨细胞调节生物材料
  • 批准号:
    10664867
  • 财政年份:
    2020
  • 资助金额:
    $ 36.86万
  • 项目类别:
Osteoclast modulatory biomaterials for skull regeneration
用于颅骨再生的破骨细胞调节生物材料
  • 批准号:
    10220944
  • 财政年份:
    2020
  • 资助金额:
    $ 36.86万
  • 项目类别:
PRECLINICAL EVALUATION OF NANOPARTICULATE MINERALIZED COLLAGEN GLYCOSAMINOGLYCAN MATERIALS IN CALVARIAL REGENERATION
纳米颗粒矿化胶原蛋白糖胺聚糖材料在颅骨再生中的临床前评估
  • 批准号:
    9906198
  • 财政年份:
    2019
  • 资助金额:
    $ 36.86万
  • 项目类别:
PRECLINICAL EVALUATION OF NANOPARTICULATE MINERALIZED COLLAGEN GLYCOSAMINOGLYCAN MATERIALS IN CALVARIAL REGENERATION
纳米颗粒矿化胶原蛋白糖胺聚糖材料在颅骨再生中的临床前评估
  • 批准号:
    10614475
  • 财政年份:
    2019
  • 资助金额:
    $ 36.86万
  • 项目类别:
PRECLINICAL EVALUATION OF NANOPARTICULATE MINERALIZED COLLAGEN GLYCOSAMINOGLYCAN MATERIALS IN CALVARIAL REGENERATION
纳米颗粒矿化胶原蛋白糖胺聚糖材料在颅骨再生中的临床前评估
  • 批准号:
    10383680
  • 财政年份:
    2019
  • 资助金额:
    $ 36.86万
  • 项目类别:
Human Bone Engineering and Resorption in a Novel Mineralized Collagen Scaffold
新型矿化胶原蛋白支架中的人体骨骼工程和吸收
  • 批准号:
    8921043
  • 财政年份:
    2015
  • 资助金额:
    $ 36.86万
  • 项目类别:
Human Bone Engineering and Resorption in a Novel Mineralized Collagen Scaffold
新型矿化胶原蛋白支架中的人体骨骼工程和吸收
  • 批准号:
    9335249
  • 财政年份:
    2015
  • 资助金额:
    $ 36.86万
  • 项目类别:
Human Bone Engineering and Resorption in a Novel Mineralized Collagen Scaffold
新型矿化胶原蛋白支架中的人体骨骼工程和吸收
  • 批准号:
    9105156
  • 财政年份:
    2015
  • 资助金额:
    $ 36.86万
  • 项目类别:

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