Biomimetic Scaffold Delivering Osteogenic Molecules for Alveolar Bone Engineering

为牙槽骨工程输送成骨分子的仿生支架

基本信息

批准号：
8434110
负责人：
Min Lee
金额：
$ 18.48万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434110
关键词：
3D Print Adverse effects Alginates Alveolar Alveolar Ridge Augmentation Alveolar ridge Apatites Architecture Biomimetics Body Fluids Bone Morphogenetic Proteins Bone Regeneration Calvaria Cells Chitosan Clinical Commit Complex Computer Assisted Craniosynostosis Custom Cyst Data Defect Dental Implants Dose Elements Environment Excision Exhibits Growth Factor Human Image Immersion Investigative Technique Implantation procedure In Vitro Kinetics Laboratories Malignant Neoplasms Mandible Marrow Maxillary Sinus Mechanics Mediating Methods Minerals Modeling Natural regeneration Nutritional Requirements Osteogenesis Patients Periodontal Diseases Physiological Platelet-Derived Growth Factor Polymers Process Property Proteins Protocols documentation Rattus Reconstructive Surgical Procedures Research Shapes Signaling Molecule Simulate Site Source Spinal Spinal Fusion Stem cells System Techniques Testing Therapeutic Tibial Fractures Tissue Engineering Tooth Loss Tooth structure Translations Trauma X-Ray Computed Tomography alveolar bone base bone bone engineering bone healing computer design in vivo meetings novel osteogenic osteogenic protein osteoinductive factor platelet-derived growth factor BB repaired scaffold

项目摘要

DESCRIPTION (provided by applicant): Periodontal disease and malignant neoplasms are devastating complications often leading to the resection of large segments of the mandible. Various osteoinductive growth factor-based therapies have been developed in an attempt to find an effective and safer method of bone regeneration. In particular, bone morphogenetic proteins (BMPs) are currently approved for spinal fusion, tibial fracture repair, and alveolar ridge or maxillary sinus augmentation. However, BMPs are highly pleiotropic molecules and their supra-physiological high dose requirement leads to adverse side effects such as cyst formation, and inefficient bone formation. Thus, there is a need to develop alternative growth factor therapeutic strategies using osteoinductive factors with more specific osteogenic effects. Nell-1 (Nel-like protein-1) is a novel osteogenic protein originally identified in active bone forming sites of human craniosynostosis patients, and is believed to specifically target cells committed to the osteogenic lineage. To provide effective and safer bone regeneration for the repair of large, complex and structural defects, we propose a novel computer-designed, biomimetic scaffolding system for controlled local delivery of Nell-1. This system will consist of three-dimensional (3D) chitosan/alginate (Chi/Al) scaffolds with well-defined geometries on the macro- and micro-scales created from an indirect 3D printing technique in conjunction with biomimetic processing strategy to confer bone mineral-mimicking apatite microenvironment and osteogenic signaling molecules (Nell-1). To maximize bone regeneration, Nell-1 will be employed also in combination with platelet-derived growth factor-BB (PDGF-BB) in clinical use for the treatment of periodontal osseous defects. The specific hypothesis of this proposal is that controlled delivery of Nell-1+PDGF from computer-designed biomimetic scaffolds can enhance repair of alveolar bone defects. To investigate this hypothesis, we propose the following aims: 1) To develop biomimetic apatite-coated Chi/Al scaffolds with controlled architectures and delivery of osteogenic molecules (Nell-1+PDGF-BB); 2) To enhance alveolar bone regeneration by biomimetic scaffolds delivering Nell-1+PDGF-BB. Chi/Al scaffold architectures that facilitate mass transport and vessel ingrowth will be created from an indirect 3D printing technique. In this construct, we will create a biomimetic apatite coating and determine if apatite layer can increase Nell-1 and PDGF delivery efficiency. The bone formation efficacy of Nell-1 from the fabricated biomimetic scaffolds will be evaluated in a larger mandibular segmental defect model. In addition, we will also incorporate PDGF into the scaffolds and assess the effects of combined Nell-1+ PDGF on bone regeneration to maximize bone formation. The results from this proposal will be critical towards clinical translation of Nell-1 mediated therapeutics to augment alveolar bone regeneration while minimizing potential adverse effects of current osteoinductive therapeutics.

描述（由申请人提供）：牙周病和恶性肿瘤是毁灭性的并发症，通常导致下颌骨大段切除。人们已经开发了各种基于骨诱导生长因子的疗法，试图找到一种有效且更安全的骨再生方法。特别是，骨形态发生蛋白（BMP）目前已被批准用于脊柱融合、胫骨骨折修复以及牙槽嵴或上颌窦增强。然而，BMP 是高度多效性的分子，其超生理的高剂量需求会导致不良副作用，例如囊肿形成和骨形成效率低下。因此，需要开发使用具有更特异性成骨作用的骨诱导因子的替代生长因子治疗策略。 Nell-1（Nel 样蛋白-1）是一种新型成骨蛋白，最初在人类颅缝早闭患者的活跃骨形成位点中发现，并被认为专门针对致力于成骨谱系的细胞。为了提供有效和更安全的骨再生来修复大型、复杂和结构性缺陷，我们提出了一种新型计算机设计的仿生支架系统，用于受控局部递送 Nell-1。该系统将由三维 (3D) 壳聚糖/藻酸盐 (Chi/Al) 支架组成，在宏观和微观尺度上具有明确的几何形状，通过间接 3D 打印技术结合仿生加工策略创建，以赋予骨矿物质-模仿磷灰石微环境和成骨信号分子（Nell-1）。为了最大限度地促进骨再生，Nell-1 还将与血小板衍生生长因子-BB (PDGF-BB) 联合用于临床治疗牙周骨缺损。该提案的具体假设是，从计算机设计的仿生支架中控制递送 Nell-1+PDGF 可以增强牙槽骨缺损的修复。为了研究这一假设，我们提出以下目标：1）开发具有受控结构和成骨分子（Nell-1+PDGF-BB）递送的仿生磷灰石涂层Chi/Al支架； 2) 通过递送 Nell-1+PDGF-BB 的仿生支架来增强牙槽骨再生。促进质量运输和血管向内生长的 Chi/Al 支架结构将通过间接 3D 打印技术创建。在此构造中，我们将创建仿生磷灰石涂层，并确定磷灰石层是否可以提高 Nell-1 和 PDGF 的递送效率。所制造的仿生支架的 Nell-1 的骨形成功效将在更大的下颌节段缺损模型中进行评估。此外，我们还将把PDGF纳入支架中，并评估组合的Nell-1+ PDGF对骨再生的影响，以最大限度地促进骨形成。该提案的结果对于 Nell-1 介导的疗法的临床转化至关重要，以增强牙槽骨再生，同时最大限度地减少当前骨诱导疗法的潜在副作用。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Adipose-derived stem cells and BMP-2 delivery in chitosan-based 3D constructs to enhance bone regeneration in a rat mandibular defect model.

基于壳聚糖的 3D 结构中的脂肪干细胞和 BMP-2 递送可增强大鼠下颌缺损模型中的骨再生。

DOI：
10.1089/ten.tea.2013.0523
发表时间：
2014-05-09
期刊：
Tissue engineering. Part A
影响因子：
0
作者：
Jiabing Fan;Hyejin Park;Matthew K Lee;O. Bezouglaia;Armita Fartash;Jinku Kim;T. Aghaloo;Min Lee
通讯作者：
Min Lee

Delivery of Phenamil Enhances BMP-2-Induced Osteogenic Differentiation of Adipose-Derived Stem Cells and Bone Formation in Calvarial Defects.

Phenamil 的递送增强了 BMP-2 诱导的脂肪干细胞的成骨分化和颅骨缺损中的骨形成。

DOI：
10.1089/ten.tea.2014.0489
发表时间：
2015-05-19
期刊：
Tissue engineering. Part A
影响因子：
0
作者：
Jiabing Fan;Choong Sung Im;Zhongjia Cui;M. Guo;O. Bezouglaia;Armita Fartash;Ju;John Nguyen;Benjamin M. Wu;T. Aghaloo;Min Lee
通讯作者：
Min Lee

Customized biomimetic scaffolds created by indirect three-dimensional printing for tissue engineering.

通过间接三维打印为组织工程创建定制仿生支架。