由天然细胞与间充质干细胞组合形成的复合组织工程全椎间盘的制造、成熟及植入。
Fabrication, maturation, and implantation of composite tissue-engineered total discs formed from native and mesenchymal stem cell combinations.
作者信息
Kim Dong Hwa, Martin John T, Gullbrand Sarah E, Elliott Dawn M, Smith Lachlan J, Smith Harvey E, Mauck Robert L
机构信息
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 308A Stemmler Hall, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, USA.
McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 308A Stemmler Hall, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA; Translational Musculoskeletal Research Center, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA 19104, USA; Department of Mechanical Engineering and Applied Mechanics, University of Pennsylvania, Philadelphia, PA, USA.
出版信息
Acta Biomater. 2020 Sep 15;114:53-62. doi: 10.1016/j.actbio.2020.05.039. Epub 2020 Jun 4.
Low back pain arising from disc degeneration is one of the most common causes of limited function in adults. A number of tissue engineering strategies have been used to develop composite tissue engineered total disc replacements to restore native tissue structure and function. In this study we fabricated a composite engineered disc based on the combination of a porous polycaprolactone (PCL) foam annulus fibrosus (AF) and a hyaluronic acid (HA) hydrogel nucleus pulposus (NP). To evaluate whether native tissue cells or mesenchymal stem cells (MSCs) would perform better, constructs were seeded with native AF/NP cells or with MSCs in the foam and/or gel region. Maturation of these composite engineered discs was evaluated for 9 weeks in vitro culture by biochemical content, histological analysis and mechanical properties. To evaluate the performance of these constructs in the in vivo space, engineered discs were implanted into the caudal spines of athymic rats for 5 weeks. Our findings show that engineered discs comprised of AF/NP cells and MSCs performed similarly and maintained their structure after 5 weeks in vivo. However, for both cell types, loss of proteoglycan was evident in the NP region. These data support the continued development of the more clinically relevant MSCs population for disc replacement applications. STATEMENT OF SIGNIFICANCE: A number of tissue engineering strategies have emerged that are focused on the creation of a composite disc replacement. We fabricated a composite engineered disc based on the combination of a porous foam AF and a HA gel NP. We used these constructs to determine whether the combination of AF/NP cells or MSCs would mature to a greater extent in vitro and which cell type would best retain their phenotype after implantation. Engineered discs comprised of AF/NP cells and MSCs performed similarly, maintaining their structure after 5 weeks in vivo. These data support the successful fabrication and in vivo function of an engineered disc composed of a PCL foam AF and a hydrogel NP using either disc cells or MSCs.
椎间盘退变引起的下腰痛是成年人功能受限的最常见原因之一。许多组织工程策略已被用于开发复合组织工程全椎间盘置换物，以恢复天然组织结构和功能。在本研究中，我们基于多孔聚己内酯（PCL）泡沫纤维环（AF）和透明质酸（HA）水凝胶髓核（NP）的组合制造了一种复合工程椎间盘。为了评估天然组织细胞或间充质干细胞（MSC）是否表现更好，构建物在泡沫和/或凝胶区域接种天然AF/NP细胞或MSC。通过生化含量、组织学分析和力学性能对这些复合工程椎间盘在体外培养9周进行成熟度评估。为了评估这些构建物在体内的性能，将工程椎间盘植入无胸腺大鼠的尾椎5周。我们的研究结果表明，由AF/NP细胞和MSC组成的工程椎间盘表现相似，在体内5周后保持其结构。然而，对于这两种细胞类型，NP区域蛋白聚糖的丢失很明显。这些数据支持继续开发更具临床相关性的MSC群体用于椎间盘置换应用。重要性声明：已经出现了许多专注于创建复合椎间盘置换物的组织工程策略。我们基于多孔泡沫AF和HA凝胶NP的组合制造了一种复合工程椎间盘。我们使用这些构建物来确定AF/NP细胞或MSC的组合在体外是否会更大程度地成熟，以及哪种细胞类型在植入后最能保留其表型。由AF/NP细胞和MSC组成的工程椎间盘表现相似，在体内5周后保持其结构。这些数据支持使用椎间盘细胞或MSC成功制造由PCL泡沫AF和水凝胶NP组成的工程椎间盘并证明其在体内的功能。
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