3D Bioprinting of Biomimetic Constructs for Rotator Cuff Augmentation

用于肩袖增强的仿生结构的 3D 生物打印

• 批准号: 10410435
• 负责人: Bin Duan
• 金额: $ 40.46万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10410435
• 关键词: 3-Dimensional; Accounting; Acute; Address; Adipose tissue; Affect; Angiogenic Factor; Animals; Architecture; Area; Autologous; Biological; Biomechanics; Biomimetics; Blood Vessels; Bone Regeneration; Cell Differentiation process; Cells; Chronic; Cicatrix; Collagen; Collagen Fiber; Data; Defect; Development; Dose; Encapsulated; Engineering; Exhibits; Extracellular Matrix; Failure; Fatty acid glycerol esters; Fibrocartilages; Fibrosis; Goals; Growth Factor; Human; Hydrogels; Impairment; Implant; In Vitro; Infiltration; Inflammation; Knowledge; Mesenchymal Stem Cells; Modeling; Muscle; Natural regeneration; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome Measure; Pattern; Phenotype; Physicians; Printing; Property; Regulation; Reporting; Role; Rotator Cuff; Shoulder Pain; Structure; Surface; Surgical sutures; System; Techniques; Technology; Tendon structure; Testing; Textiles; Therapeutic; Thick; Tissue constructs; Tissues; Translating; United States; Vascularization; Visit; Work; Xenograft procedure; base; bioink; bioprinting; bone; bone healing; design; healing; improved; in vitro regeneration; in vivo; infraspinatous muscle; innovative technologies; mechanical properties; nanofiber; novel strategies; osteogenic; primary outcome; repaired; rotator cuff injury; rotator cuff tear; scaffold; stem cell differentiation; stem cells; tissue regeneration; treatment strategy

Project Summary Rotator cuff tendon tears account for more than 4.5 million physician visits per year, and over 250,000 rotator cuff repair surgeries are performed annually in the United States. For massive rotator cuff defect or chronic tears with significant retraction and tissue loss, multiple strategies, including auto-, allo- and xenografts as well as synthetic implants, have been used to augment the bone-tendon junction to improve the rates of successful healing of these severe rotator cuff tears. Despite the current advances in tissue augmentation, the overall failure rate has been reported to be between 38% and 65%. Obstacles in the development of approaches to address tendon-to-bone healing are partly because (1) current augmentation options fail to mimic multizoal structure of native rotator cuff tissue; (2) uniform matrix microenvironment impedes the heterogeneous differentiation and vascularization of progenitor cells/mesenchymal stem cells (MSC); (3) limited knowledge has been gained about how MSC differentiation status and vascularization pattern within different zonal region affect rotator cuff healing. We have developed a novel strategy by combining 3D bioprinting technique with biotextile technique to generate engineered rotator cuff constructs with zonal structure and spatial bioactive factor distribution. The proposed studies will test the hypothesis that tendon-to-bone regeneration is enhanced in vitro and in vivo by spatial differentiation of adipose derived MSC (ADMSC) and spatial control of vascularization degree in pre-designed region in the optimized bioprinted microenvironment. The specific aims of the studies are (i) determine how spatial differentiation of ADMSC within bioprinted rotator cuff constructs affect tendon-to-bone healing; and (ii) determine how the spatially incorporated bioactive factors regulate ADMSC differentiation, vascularization and rotator cuff repair. A massive rabbit infraspinatus tendon defect model will be employed for both of the aims. The primary outcome measures will include inflammation, construct integration, collagen fiber alignment, collagen types in different regions, muscle quality and fat infiltration, and tensile biomechanics. This proposal will develop biological augmentation strategies to promote scarless healing. Our approach is to better understand the roles of exogenous stem cells and vasculature on tendon-to-bone interface regeneration in vitro and in vivo.

项目概要 肩袖肌腱撕裂每年导致超过 450 万人次就诊，超过 250,000 名肩袖肌腱撕裂患者 美国每年都会进行袖带修复手术。对于大量肩袖缺损或慢性 具有显着回缩和组织损失的撕裂，采用多种策略，包括自体移植、同种异体移植和异种移植 作为合成植入物，已用于增强骨肌腱连接以提高成功率 治愈这些严重的肩袖撕裂。尽管目前组织增强方面取得了进展，但总体而言 据报道，失败率在 38% 至 65% 之间。开发方法中的障碍 解决肌腱到骨愈合的部分原因是（1）当前的增强选项无法模仿多动物 原生肩袖组织的结构； (2)均匀的基质微环境阻碍了异质 祖细胞/间充质干细胞（MSC）的分化和血管化； (3)知识有限 已获得不同带状区域内 MSC 的分化状态和血管化模式 影响肩袖愈合。我们通过将 3D 生物打印技术与 生物纺织技术可生成具有区域结构和空间生物活性的工程肩袖结构 因子分布。拟议的研究将检验肌腱到骨骼再生得到增强的假设 通过脂肪源性 MSC (ADMSC) 的空间分化和空间控制，在体外和体内 优化生物打印微环境中预先设计区域的血管化程度。具体目标 这些研究包括 (i) 确定生物打印的肩袖结构中 ADMSC 的空间分化如何 影响肌腱至骨骼的愈合； (ii) 确定空间结合的生物活性因子如何调节 ADMSC 分化、血管化和肩袖修复。兔冈下肌腱巨大缺损 模型将用于这两个目标。主要结果指标包括炎症、 结构整合、胶原纤维排列、不同区域的胶原蛋白类型、肌肉质量和脂肪 渗透和拉伸生物力学。该提案将制定生物增强策略以促进 无疤愈合。我们的方法是更好地了解外源干细胞和脉管系统对 体外和体内肌腱-骨界面再生。

项目成果

Platelet-Rich Plasma Therapy in the Treatment of Diseases Associated with Orthopedic Injuries.

富血小板血浆疗法治疗骨科损伤相关疾病。

• 发表时间: 2020
• 作者: Fang, Jie;Wang, Xin;Jiang, Wen;Zhu, Yaqiong;Hu, Yongqiang;Zhao, Yanxu;Song, Xueli;Zhao, Jinjuan;Zhang, Wenlong;Peng, Jiang;Wang, Yu
• 通讯作者: Wang, Yu

3D printing of multilayered scaffolds for rotator cuff tendon regeneration.

用于肩袖肌腱再生的多层支架的 3D 打印。

• 发表时间: 2020-09
• 影响因子: 18.9
• 作者: Jiang, Xiping;Wu, Shaohua;Kuss, Mitchell;Kong, Yunfan;Shi, Wen;Streubel, Philipp N;Li, Tieshi;Duan, Bin
• 通讯作者: Duan, Bin

Electrospun conductive nanofiber yarns for accelerating mesenchymal stem cells differentiation and maturation into Schwann cell-like cells under a combination of electrical stimulation and chemical induction.

静电纺导电纳米纤维纱线，可在电刺激和化学诱导的结合下加速间充质干细胞分化和成熟为雪旺细胞样细胞。

• 发表时间: 2022-02
• 影响因子: 9.7
• 作者: Wu, Shaohua;Qi, Ye;Shi, Wen;Kuss, Mitchell;Chen, Shaojuan;Duan, Bin
• 通讯作者: Duan, Bin

TLR2 and caspase-1 signaling are critical for bacterial containment but not clearance during craniotomy-associated biofilm infection.

TLR2 和 caspase-1 信号传导对于细菌遏制至关重要，但在开颅手术相关生物膜感染期间对细菌清除至关重要。

• 发表时间: 2020-04-14
• 作者: Aldrich, Amy L;Heim, Cortney E;Shi, Wen;Fallet, Rachel W;Duan, Bin;Kielian, Tammy
• 通讯作者: Kielian, Tammy

Red blood cell membrane-camouflaged poly(lactic-co-glycolic acid) microparticles as a potential controlled release drug delivery system for local stellate ganglion microinjection.

红细胞膜伪装的聚（乳酸-乙醇酸）微粒作为局部星状神经节显微注射的潜在控释药物递送系统。

• DOI: 10.1016/j.actbio.2023.02.030
• 发表时间: 2023-02-01
• 期刊: Acta biomaterialia
• 影响因子: 9.7
• 作者: Bo Liu;Dongze Zhang;H. Tu;O. A. Alimi;Yunfan Kong;Rachagani Satyanarayana;Mitchell A. Kuss;Yulo
• 通讯作者: Yulo