Self-assembling Biomimetic Hydrogels with Bioadhesive Properties for Intervertebr

具有生物粘附特性的椎间自组装仿生水凝胶

基本信息

批准号：
8434338
负责人：
Andrea Jennifer Vernengo
金额：
$ 31.59万
依托单位：
ROWAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-16 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8434338
关键词：
Adherence Adhesions Adhesives Adipose tissue Adult Aldehydes Amines Anti-Inflammatory Agents Anti-inflammatory Area Biochemical Biocompatible Biological Biomimetics Biopolymers Body part Cell Survival Cells Characteristics Chondroitin Sulfates Collagen Consensus Development Dislocations Drug Formulations Encapsulated Engineering Environment Exhibits Extracellular Matrix Extracellular Matrix Proteins Family Fibrin Tissue Adhesive Foundations Gel Gelatin Growth Factor Hydrogels Implant In Situ In Vitro Injectable Injection of therapeutic agent Intervertebral disc structure Lipids Liposomes Low Back Pain Mechanics Medical Natural regeneration Needles Nutrient Organ Orthopedics Phenotype Physiological Polymers Property Proteins Proteoglycan Reaction Regenerative Medicine Research Personnel Risk Schiff Bases Shear Strength Solutions Stem cells Structure Suspension substance Suspensions System Technology Temperature Time Tissue Engineering Tissues Vesicle Water Weight-Bearing state Work absorption aqueous base biomaterial compatibility copolymer cytotoxic design disc regeneration implantation in vivo mRNA Expression melting multidisciplinary next generation novel novel strategies nucleus pulposus poly-N-isopropylacrylamide prevent public health relevance repaired scaffold success tissue regeneration transmission process treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Tissue engineering is a multidisciplinary field that aims to repair or regenerate lost or damaged tissues and organs in the body. The foundation of tissue engineering encompasses three fundamental strategies, specifically cellular, biochemical, and scaffold-based approaches. For the repair of certain load-bearing parts of the body, success of a tissue regeneration strategy can be dependent on scaffold adhesion or integration with the surrounding host tissue to prevent dislocation. One such area is the regeneration of the nucleus pulposus (NP) of the intervertebral disc (IVD). Tissue engineering of the NP is regarded as a potential strategy for the treatment of lower back pain, one of the most common medical problems in the world. Several researchers have focused on seeding cells in three-dimensional matrices to achieve formation of a new NP matrix. Studies have also shown that adipose derived stem cells (ASCs) can be differentiated into NP-like cells in vitro and in vivo. While these findings are promising, next generation NP engineering scaffolds must have the ability to form a substantial interface with surrounding disc tissue. This will reduce or eliminate the risk o dislocation in the disc and help to provide adequate transmission of force across the interface between the implant and the tissue. Although scaffold integration with tissue can be achieved using a bioadhesive polymer, the currently proposed materials with high adhesive properties have limited biocompatibility. A need for bioadhesive polymers exists in the area of regenerative medicine. The design of a material that covalently bonds with surrounding extracellular matrix components and provides an environment permissive to the survival and differentiation of encapsulated cells would be a major step forward not just in IVD engineering, but in orthopedic tissue engineering, in general. In this proposal, we detail the development of a novel "smart" hydrogel for ASC encapsulation, partially composed of the thermally sensitive polymer poly(N-isopropylacrylamide) (PNIPAAm). Below its lower critical solution temperature (LCST) at 32C, the polymer forms a miscible solution with water. Above the LCST, it becomes hydrophobic, so the polymer and water separate, forming a compact gel. Therefore, aqueous solutions of PNIPAAm can be implanted non-invasively through a small gauge needle and solidify in situ. The biopolymer chondroitin sulfate (CS), an ECM component of the native IVD tissue, is incorporated into the PNIPAAm matrix to form a semi-synthetic injectable hydrogel with the favorable mechanical characteristics of PNIPAAm and the enzymatic degradability, anti-inflammatory activity, water and nutrient absorption of CS. In addition, CS can be modified with aldehyde groups (CS aldehyde), allowing it to react with amines via Schiff's base reaction, thus rendering the hydrogel bioadhesive upon contact with amines of the extracellular matrix proteins. However, the presence of the reactive aldehyde groups can compromise the viability of encapsulated cells. The novel strategy in this proposal is to circumvent this problem with the inclusion of liposomes designed to deliver ECM components after the polymer has adhered to tissue and reached physiological temperature. The discharge of ECM components will enhance the biocompatibility of the material by marking the assembly of a biomimetic matrix, and also covalently reacting with, or "end-capping", the aldehyde functionalities within the gel that did no participate in bonding with tissue upon contact. This work is based on the hypothesis that the three-component bioadhesive (PNIPAAm, CS aldehyde, and ECM-loaded liposomes) will support long term viability and differentiation of ASCs toward a NP phenotype, making it a feasible three- dimensional culture system for use in IVD tissue engineering.

描述（由申请人提供）：组织工程是一个多学科领域，旨在修复或再生体内丢失或受损的组织和器官。组织工程的基础包括三种基本策略，特别是细胞、生化和基于支架的方法。对于身体某些承重部位的修复，组织再生策略的成功可能取决于支架与周围宿主组织的粘附或整合以防止脱位。其中之一就是椎间盘（IVD）髓核（NP）的再生。 NP 的组织工程被认为是治疗腰痛的潜在策略，腰痛是世界上最常见的医学问题之一。一些研究人员专注于在三维矩阵中接种细胞，以实现新的纳米粒子矩阵的形成。研究还表明，脂肪源性干细胞（ASC）可以在体外和体内分化为 NP 样细胞。虽然这些发现很有希望，但下一代 NP 工程支架必须能够与周围的椎间盘组织形成实质性界面。这将减少或消除椎间盘脱位的风险，并有助于在植入物和组织之间的界面上提供足够的力传递。尽管可以使用生物粘附聚合物实现支架与组织的整合，但目前提出的具有高粘附特性的材料具有有限的生物相容性。再生医学领域存在对生物粘附聚合物的需求。设计一种与周围细胞外基质成分共价结合并提供有利于封装细胞生存和分化的环境的材料不仅是 IVD 工程的重大进步，而且是骨科组织工程的重大进步。在本提案中，我们详细介绍了一种用于 ASC 封装的新型“智能”水凝胶的开发，该水凝胶部分由热敏聚合物聚（N-异丙基丙烯酰胺）（PNIPAAm）组成。低于 32°C 的下临界溶液温度 (LCST)，聚合物会形成与水混溶的溶液。高于 LCST，它变得疏水，因此聚合物和水分离，形成致密的凝胶。因此，PNIPAAm 的水溶液可以通过小规格针非侵入性地植入并在原位固化。生物聚合物硫酸软骨素 (CS) 是天然 IVD 组织的 ECM 成分，被纳入 PNIPAAm 基质中，形成半合成可注射水凝胶，具有 PNIPAAm 良好的机械特性以及酶降解性、抗炎活性、水和CS的营养吸收。此外，CS可以用醛基（CS醛）修饰，使其能够通过希夫碱反应与胺发生反应，从而使水凝胶在与细胞外基质蛋白的胺接触时具有生物粘附性。然而，反应性醛基的存在会损害封装细胞的活力。该提案中的新策略是通过包含脂质体来规避这个问题，该脂质体旨在在聚合物粘附到组织并达到生理温度后递送 ECM 成分。 ECM 组分的放电将通过标记仿生基质的组装来增强材料的生物相容性，并且还与凝胶内的醛官能团发生共价反应或“封端”，该官能团在接触时不参与与组织的结合。这项工作基于以下假设：三组分生物粘附剂（PNIPAAm、CS 醛和 ECM 负载脂质体）将支持 ASC 的长期生存能力和向 NP 表型的分化，使其成为可行的三维培养系统IVD 组织工程。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

Using embedded alginate microparticles to tune the properties of in situ forming poly(N-isopropylacrylamide)-graft-chondroitin sulfate bioadhesive hydrogels for replacement and repair of the nucleus pulposus of the intervertebral disc.

使用嵌入的藻酸盐微粒来调节原位形成的聚（N-异丙基丙烯酰胺）-移植物-硫酸软骨素生物粘附水凝胶的性能，用于椎间盘髓核的置换和修复。

DOI：
发表时间：
2021-09
期刊：
影响因子：
3.7
作者：
Christiani, Thomas;Mys, Karen;Dyer, Karl;Kadlowec, Jennifer;Iftode, Cristina;Vernengo, Andrea Jennifer
通讯作者：
Vernengo, Andrea Jennifer

Thermogelling bioadhesive scaffolds for intervertebral disk tissue engineering: preliminary in vitro comparison of aldehyde-based versus alginate microparticle-mediated adhesion.

用于椎间盘组织工程的热凝胶生物粘附支架：基于醛的粘附与藻酸盐微粒介导的粘附的初步体外比较。

DOI：
发表时间：
2015-04
期刊：
影响因子：
9.7
作者：
Wiltsey, C;Christiani, T;Williams, J;Scaramazza, J;Van Sciver, C;Toomer, K;Sheehan, J;Branda, A;Nitzl, A;England, E;Kadlowec, J;Iftode, C;Vernengo, J
通讯作者：
Vernengo, J

Synthesis of Thermogelling Poly(N-isopropylacrylamide)-graft-chondroitin Sulfate Composites with Alginate Microparticles for Tissue Engineering.

用于组织工程的热凝胶聚（N-异丙基丙烯酰胺）-接枝硫酸软骨素复合物与海藻酸盐微粒的合成。

DOI：
发表时间：
2016
期刊：
影响因子：
0
作者：
Christiani, Thomas R;Toomer, Katelynn;Sheehan, Joseph;Nitzl, Angelika;Branda, Amanda;England, Elizabeth;Graney, Pamela;Iftode, Cristina;Vernengo, Andrea J
通讯作者：
Vernengo, Andrea J

Intraoperative changes in transcranial motor evoked potentials and somatosensory evoked potentials predicting outcome in children with intramedullary spinal cord tumors.

经颅运动诱发电位和体感诱发电位的术中变化可预测髓内脊髓肿瘤儿童的预后。