The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.
The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.
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DOI：
10.1016/j.actbio.2017.08.005
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发表时间：
2017-10-01
影响因子：
9.7
通讯作者：
Malda J
中科院分区：
文献类型：
--
作者：
Levato R;Webb WR;Otto IA;Mensinga A;Zhang Y;van Rijen M;van Weeren R;Khan IM;Malda J
细胞水凝胶是生物打印的主要构件，也被称为生物墨水，是创建潜在地重现关节软骨结构的结构的基础。为了发挥功能，水凝胶结构需要解锁被包裹的细胞的再生能力。新近发现的关节软骨多能驻留软骨前体细胞具有成体干细胞的重要特性，为软骨再生提供了新的契机。然而，对于ACPC在组织工程中的适用性，尤其是与生物材料的结合，人们知之甚少。本研究旨在研究水凝胶中的ACPC在软骨再生和生物制造方面的潜力，并评估其产生区域特异性基质的能力。将明胶甲基丙烯酰基(GelMA)水凝胶用于培养ACPC、骨髓间充质干细胞(MSCs)和软骨细胞，并作为生物墨水用于打印。我们的数据显示，ACPC在新生软骨生成方面优于软骨细胞，而且与MSCs不同，ACPC肥大标志物X型胶原的基因表达水平最低，而关节润滑的关键因素PRG4的基因表达水平最高。细胞类型在多室水凝胶中的共培养允许产生具有分层分布的胶原蛋白和糖胺多聚糖的构建体。通过结合ACPC和MSC负载的生物墨水，产生了一个生物打印的关节软骨模型，包括明确的浅层和深层区域，每个区域都有不同的细胞和细胞外基质组成。综上所述，这些结果为ACPC水凝胶在再生医学中的应用提供了重要的信息，并为构建具有多种细胞类型的三维结构用于软骨再生或体外组织模型铺平了道路。
Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3 D constructs with multiple cell types for cartilage regeneration or in vitro tissue models.
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影响因子：
4.6
作者：
Fellows CR;Williams R;Davies IR;Gohil K;Baird DM;Fairclough J;Rooney P;Archer CW;Khan IM
通讯作者：
Khan IM
影响因子：
4.8
作者：
Bhumiratana, Sarindr;Vunjak-Novakovic, Gordana
通讯作者：
Vunjak-Novakovic, Gordana
影响因子：
9.7
作者：
Boere, Kristel W. M.;Visser, Jetze;Malda, Jos
通讯作者：
Malda, Jos
影响因子：
3.2
作者：
Hayes, Anthony J.;Tudor, Debbie;Hughes, Clare E.
通讯作者：
Hughes, Clare E.
DOI：
10.1115/1.4005851
发表时间：
2012-03
期刊：
Journal of biomechanical engineering
影响因子：
--
作者：
Balcom NT;Berg-Johansen B;Dills KJ;Van Donk JR;Williams GM;Chen AC;Hazelwood SJ;Sah RL;Klisch SM
通讯作者：
Klisch SM