3D printed muscle-bone organ implant for treating large injuries

3D打印肌肉骨骼器官植入物用于治疗大面积损伤

基本信息

批准号：
10393059
负责人：
Mehmet Remzi Dokmeci
金额：
$ 41.79万
依托单位：
TERASAKI INSTITUTE FOR BIOMEDICAL INNOVATION
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：
2020-11-19 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10393059
关键词：
3-Dimensional 3D Print Address Affect American Amputation Area Behavior Biodegradation Biological Bioreactors Bone Development Bone Diseases Bone Growth Bone Tissue Bone neoplasms Burn injury Cells Cessation of life Clinic Clinical Coupled Custom Defect Development Differentiation and Growth Disease Distal Drug Carriers Encapsulated Engineering Ewings sarcoma External Intercostal Muscle Femur Fibrosis Goals Growth Growth Factor Growth Factor Receptors Growth and Development function Health Human Hydrogels Impairment Implant In Vitro Individual Injectable Injections Injury Ink Kinetics Lead Malignant Neoplasms Medical Modeling Movement Mus Muscle Muscle Cells Muscle function Muscular Atrophy Musculoskeletal Musculoskeletal Diseases Musculoskeletal System Natural regeneration Operative Surgical Procedures Organ Osteoblasts Pain Pathologic Patients Perfusion Periosteum Persons Population Porosity Printing Property Recovery Regenerative Medicine Regenerative capacity Relaxation Research Signal Transduction Site Structure System Technology Therapeutic Tissues United States Viscosity automobile accident base bioink biomaterial compatibility bioprinting bone bone cell bone epiphysis cell type controlled release design disability immunoregulation improved in vivo infraspinatous muscle innovation limb injury macrophage mimetics mortality muscular structure musculoskeletal injury osteogenic osteosarcoma physically handicapped pressure prevent recruit socioeconomics soft tissue three dimensional structure tissue regeneration tumor volumetric muscle loss

项目摘要

PROJECT SUMMARY In the United States, musculoskeletal diseases such as extremity injuries, burns, and tumors are a leading cause of disabilities and death, affecting one in two individuals. However, until now, there has been no effective implant that can replace the structure and function of damaged bone and muscle tissues, likely due to the difficulty of regulating the sophisticated heterogeneous bone-muscle junction structure. As a result, muscle damage has been largely ignored during musculoskeletal surgeries, which often results in disconnected tissues and fibrous tissue formation, leading to temporal or permanent musculoskeletal disability. In fact, in the human musculoskeletal system, there exists a direct attachment between bone and muscle tissues at a wide area of bone, forming a “bone-muscle unit.” Based on this structural closeness, the growth and development of bone and muscle are tightly coupled through growth factor signaling and cellular cross-talk. Therefore, damage to either bone or muscle can deteriorate health and function of the other tissue type. For this reason, there has been a strong need for developing an innovative musculoskeletal implant, which can integrate the distinguished physicochemical properties of hard tissue and soft tissue in a spatially controlled manner. To address this problem, we aim to design and build the first 3D printed muscle-bone implant, by utilizing state- of-the-art 3D multimaterial bioprinting that can extrude multiple types of tissue mimetic bioinks in a simultaneous and continuous manner. We will control the physicochemical properties of bioinks, such as viscosity and porosity, to provide an optimized artificial niche for the growth and differentiation of each cell type. We will also include biodegradable drug carriers to supply musculogenic and osteogenic growth factors with controlled release kinetic behavior, to aid tissue recovery. In addition, we will regulate the parameters for bioprinting, such as pneumatic pressure, and the injection and photocrosslinking conditions to build a 3D structure. We will then mature the 3D printed muscle-bone organ implant in a customized bioreactor system by applying compression and relaxation cycles that mimic musculoskeletal movement in vivo. Finally, we will evaluate the musculoskeletal regeneration capacity of our 3D printed muscle-bone implant in a mouse volumetric muscle loss and bone defect model. This research will present the first 3D print muscle-bone tissues with continuous structures ex vivo that can provide a groundbreaking clinical solution for curing severe musculoskeletal injuries and preventing disabilities in the clinic. We further expect that our 3D printed muscle-bone tissue platform will be beneficial for understanding developmental principles and pathological mechanisms of the musculoskeletal system.

项目概要在美国，四肢受伤、烧伤和肿瘤等肌肉骨骼疾病是导致死亡的主要原因残疾和死亡，影响了二分之一的人。然而，到目前为止，还没有有效的植入物。它可以替代受损的骨骼和肌肉组织的结构和功能，这可能是由于修复的难度调节复杂的异质骨-肌肉连接结构，从而导致肌肉损伤。在肌肉骨骼手术期间很大程度上被忽视，这通常会导致组织断开和纤维化事实上，在人类中，会导致暂时性或永久性的肌肉骨骼残疾。在肌肉骨骼系统中，骨骼和肌肉组织之间在大范围内存在直接附着骨骼，形成“骨-肌肉单元”。基于这种结构的紧密性，骨骼的生长和发育。和肌肉通过生长因子信号传导和细胞串扰紧密耦合，因此会造成损害。骨骼或肌肉都会损害其他组织类型的健康和功能。强烈需要开发一种创新的肌肉骨骼植入物，它可以整合杰出的以空间控制的方式检测硬组织和软组织的物理化学特性。为了解决这个问题，我们的目标是利用状态设计和制造第一个 3D 打印肌肉骨植入物最先进的 3D 多材料生物打印，可以同时挤出多种类型的组织模拟生物墨水我们将控制生物墨水的物理化学性质，例如粘度和孔隙率，为每种细胞类型的生长和分化提供优化的人工生态位。可生物降解的药物载体，提供具有控制释放动力学的肌肉生成和成骨生长因子此外，我们将调节生物打印的参数，例如气动。压力、注射和光交联条件来构建 3D 结构，然后我们将使 3D 成熟。通过施加压缩和放松，在定制的生物反应器系统中打印肌肉骨器官植入物最后，我们将评估肌肉骨骼再生。我们的 3D 打印肌肉骨植入物在小鼠体积肌肉损失和骨缺损模型中的能力。研究将展示第一个具有连续结构的离体 3D 打印肌肉骨组织，可以提供用于治疗严重肌肉骨骼损伤和预防临床残疾的突破性临床解决方案。我们进一步期望我们的 3D 打印肌肉骨骼组织平台将有助于理解肌肉骨骼系统的发育原理和病理机制。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nanotherapeutic approaches to overcome distinct drug resistance barriers in models of breast cancer.

DOI：
10.1515/nanoph-2021-0142
发表时间：
2021-09
期刊：
Nanophotonics
影响因子：
7.5
作者：
Saha T;Mondal J;Khiste S;Lusic H;Hu ZW;Jayabalan R;Hodgetts KJ;Jang H;Sengupta S;Eunice Lee S;Park Y;Lee LP;Goldman A
通讯作者：
Goldman A

An inexpensive "do-it-yourself" device for rapid generation of uniform tumor spheroids.

DOI：
10.1016/j.device.2024.100255
发表时间：
2024-01
期刊：
Device
影响因子：
0
作者：
Bumseok Namgung;Hongqing Dai;P. Vikraman;Tanmoy Saha;Shiladitya Sengupta;Hae Lin Jang
通讯作者：
Bumseok Namgung;Hongqing Dai;P. Vikraman;Tanmoy Saha;Shiladitya Sengupta;Hae Lin Jang

Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype.

DOI：
10.3390/ijms22116161
发表时间：
2021-06-07
期刊：
International journal of molecular sciences
影响因子：
5.6
作者：
Dash C;Saha T;Sengupta S;Jang HL
通讯作者：
Jang HL

Template-Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels.

DOI：
10.1002/adhm.202102123
发表时间：
2022-04
期刊：
Advanced healthcare materials
影响因子：
10
作者：
Davoodi E;Montazerian H;Zhianmanesh M;Abbasgholizadeh R;Haghniaz R;Baidya A;Pourmohammadali H;Annabi N;Weiss PS;Toyserkani E;Khademhosseini A
通讯作者：
Khademhosseini A

Human Nonalcoholic Steatohepatitis on a Chip.