Oxygen generating bioinks for 3D printed bone implants

用于 3D 打印骨植入物的产氧生物墨水

• 批准号: 10425405
• 负责人: Su Ryon Shin
• 金额: $ 37.87万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-17 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425405
• 关键词: 3-Dimensional; Address; Alginates; Anastomosis - action; Autologous Transplantation; Behavior; Biocompatible Materials; Blood Vessels; Bone Tissue; Bone Transplantation; Cell Death; Cell Survival; Cells; Clinical; Defect; Development; Diffusion; Endothelial Cells; Engineering; Excision; Failure; Fracture; Gelatin; Goals; Gold; Hospitalization; Human; Hydrolysis; Hydrophobicity; Hypoxia; Implant; In Vitro; Intuition; Mesenchymal Stem Cells; Modeling; Morbidity - disease rate; Musculoskeletal; Nature; Orthopedic Procedures; Osteogenesis; Oxygen; Pain; Patients; Phase; Polymers; Recovery; Research; Safety; Silicates; Site; Solid; Starvation; Stress; Structure; System; Techniques; Technology; Time; Tissue Engineering; Tissue constructs; Tissues; Ultraviolet Rays; United States; Vascular Endothelial Cell; Vascular System; Vascularization; behavioral construct; bioink; bioprinting; blood vessel development; bone; bone engineering; bone fracture repair; clinical efficacy; clinically relevant; cost; crosslink; design; disability; healing; implantation; improved; in vivo; innovation; long bone; nanoparticle; novel; osteogenic; physically handicapped; prevent; sample fixation; standard care; subcutaneous; tissue injury

Abstract Musculoskeletal tissue injuries are a leading cause of disability in the United States (US), yet there are only a few viable options for patients suffering from bone degeneration. One of the major challenges in this field is nonunion formation, which is the permanent failure of bone fracture healing. Current therapies such as bone fixation or bone grafting are often ineffective, painful, invasive, costly, and do not result in recovery of full function. To overcome this grand challenge, much research has been dedicated to the development of engineered three- dimensional (3D) bone tissue, which typically is composed of a biomaterial containing human mesenchymal stem cells (hMSCs) for bone formation and endothelial cells for blood vessel formation. Although these approaches accelerate implant anastomosis, it is inherently still associated with a prevascular phase that causes significant amounts of starvation induced cell death. Here, we propose an innovative solution to solve this important problem. We aim to achieve this by developing an oxygen generating biomaterial that can be used to 3D bioprint a vascularized bone implant for critical bone defect treatments. To this end, we set-out to explore two of our recently developed technologies: oxygen generating biomaterials and embedded sacrificial 3D bioprinting. To maintain cell survival during the implant’s pre-anastomosis phase, we will develop hydrophobic micromaterials containing molecules that release oxygen upon hydrolysis, which can be controlled via tuning the micromaterial’s hydrophobicity. These microparticles will be combined with our 3D printable and bone forming nanoparticle incorporated biomaterial matrix (Silicate-nanoparticles/GelMA) that is laden with human mesenchymal stem cells to effectively create an oxygenating bone forming bioink. This bioink will be used as a viscous medium in which a 3D vascular structure will be printed using embedded bioprinting; a novel 3D bioprinting technique that we are pioneering. Specifically, we will endow constructs with a 3D vascular structure of endothelial cell laden alginate bioink. Crosslinking the oxygenating bioink using low levels of UV light will yield a fully solid 3D construct. Upon sacrificing the internal alginate structure, an open 3D vascular network will be instantly formed. The pre-laden endothelial cells will coat the 3D network and thus provide a functional early vascularity that will accelerate anastomosis and thus minimize the implant’s prevascular phase. After in depth in vitro characterization using normoxic and hypoxic cultures, we will investigate the construct’s in vivo behavior using a subcutaneous and a critical defect model.

摘要

项目成果

Ferritin Nanocage Conjugated Hybrid Hydrogel for Tissue Engineering and Drug Delivery Applications.

• DOI: 10.1021/acsbiomaterials.9b01482
• 发表时间: 2020-01-13
• 期刊: ACS biomaterials science & engineering
• 影响因子: 5.8
• 作者: Samanipour R;Wang T;Werb M;Hassannezhad H;Rangel JML;Hoorfar M;Hasan A;Lee CK;Shin SR
• 通讯作者: Shin SR

Oxygen-Releasing Biomaterials: Current Challenges and Future Applications.

• DOI: 10.1016/j.tibtech.2021.01.007
• 发表时间: 2021-11
• 期刊: TRENDS IN BIOTECHNOLOGY
• 影响因子: 17.3
• 作者: Willemen, Niels G. A.;Hassan, Shabir;Gurian, Melvin;Li, Jinghang;Allijn, Iris E.;Shin, Su Ryon;Leijten, Jeroen
• 通讯作者: Leijten, Jeroen

Flexible and Stretchable PEDOT-Embedded Hybrid Substrates for Bioengineering and Sensory Applications.

• DOI: 10.1002/cnma.201900146
• 发表时间: 2019-06
• 期刊: ChemNanoMat : chemistry of nanomaterials for energy, biology and more
• 作者: Fallahi A;Mandla S;Kerr-Phillip T;Seo J;Rodrigues RO;Jodat YA;Samanipour R;Hussain MA;Lee CK;Bae H;Khademhosseini A;Travas-Sejdic J;Shin SR
• 通讯作者: Shin SR

Enzyme-Mediated Alleviation of Peroxide Toxicity in Self-Oxygenating Biomaterials.

酶介导减轻自氧化生物材料中的过氧化物毒性。

• DOI: 10.1002/adhm.202102697
• 发表时间: 2022
• 期刊: Advanced healthcare materials
• 影响因子: 10
• 作者: Willemen,NielsGA;Hassan,Shabir;Gurian,Melvin;Jasso-Salazar,MariaFernanda;Fan,Kai;Wang,Haihang;Becker,Malin;Allijn,IrisE;Bal-Öztürk,Ayça;Leijten,Jeroen;Shin,SuRyon
• 通讯作者: Shin,SuRyon

Self-oxygenation of engineered living tissues orchestrates osteogenic commitment of mesenchymal stem cells.

• DOI: 10.1016/j.biomaterials.2023.122179
• 发表时间: 2023-05
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Shabir Hassan;Ting Wang;Kun Shi;Yike Huang;Mariely Urbina;Kaifeng Gan;Mo Chen;Niels G A Willemen;Haroon Kalam;E. Luna-Ceron;Berivan Çeçen;Gihan Daw Elbait;Jinghang Li;Luis Enrique García-Rivera;Melvin Gurian;Mudassir Meraj Banday;Kisuk Yang;M. C. Lee;Weida Zhuang;Castro Johnbosco;Oju Jeon;E. Alsberg;J. Leijten;S. Shin