Gravity-based patterning of osteogenic factors to preserve bone structure after osteochondral injury in a large animal model.
Gravity-based patterning of osteogenic factors to preserve bone structure after osteochondral injury in a large animal model.
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DOI：
10.1088/1758-5090/ac79cd
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发表时间：
2022-07-05
期刊：
影响因子：
9
通讯作者：
Mauck, Robert L.
中科院分区：
文献类型：
--
作者：
Zlotnick, Hannah M.;Locke, Ryan C.;Hemdev, Sanjana;Stoeckl, Brendan D.;Gupta, Sachin;Peredo, Ana P.;Steinberg, David R.;Carey, James L.;Lee, Daeyeon;Dodge, George R.;Mauck, Robert L.
软骨和骨软骨修复策略受到损伤后发生的不良骨变化的限制。骨吸收可以导致整个支架，工程组织，甚至内源性修复组织下沉到软骨表面以下。为了解决这一转化问题，我们制作了含有促成骨剂三碘甲状腺原氨酸和ß-甘油磷酸酯的厚壳聚（D， l -乳酸-羟基乙酸酯）（PLGA）微胶囊，并将这些微胶囊输送到大型骨软骨损伤动物模型中以保护骨结构。我们证明了开发的微胶囊在体外机械载荷增加的情况下破裂，并且很容易在液体溶液中下沉，使骨软骨表面的重力模式成为可能。在大型动物中，通过两种不同的递送策略对这些机械激活微胶囊（MAMCs）进行了评估。关节内注射对照MAMC，可以在体内对滑膜关节内的MAMC破裂和货物释放进行荧光量化。这种全关节注射也证实了mmcs不会引起炎症反应。在对侧后肢，创建软骨缺损，原位绘制mmcs，并进行纳米骨折（Nfx），这是一种临床使用的促进软骨修复的方法。NFx孔使骨髓来源的基质细胞能够进入缺损区域，并作为可重复的骨损伤部位进行长期监测。动物在注射和手术后1周和2周进行评估。对注射的MAMCs的分析表明，生物活性货物在2周内以受控的方式释放。手术时注射的骨荧光标记显示治疗组维持矿物质标记，但两个对照组均有吸收。骨软骨界面碱性磷酸酶（AP）染色显示，在治疗性MAMCs治疗的缺陷中，AP活性较高。总的来说，本研究发展了一种基于重力的方法来沿着骨软骨界面模式生物活性因子，并将这种新的生物制造策略应用于骨软骨损伤后的骨结构保护。
Chondral and osteochondral repair strategies are limited by adverse bony changes that occur after injury. Bone resorption can cause entire scaffolds, engineered tissues, or even endogenous repair tissues to subside below the cartilage surface. To address this translational issue, we fabricated thick-shelled poly(D,L-lactide-co-glycolide) (PLGA) microcapsules containing the pro-osteogenic agents triiodothyronine and ß-glycerophosphate, and delivered these microcapsules in a large animal model of osteochondral injury to preserve bone structure. We demonstrate that the developed microcapsules ruptured in vitro under increasing mechanical loads, and readily sink within a liquid solution, enabling gravity-based patterning along the osteochondral surface. In a large animal, these mechanically-actived microcapsules (MAMCs) were assessed through two different delivery strategies. Intra-articular injection of control MAMCs enabled fluorescent quantification of MAMC rupture and cargo release in a synovial joint setting over time in vivo. This joint-wide injection also confirmed that the MAMCs do not elicit an inflammatory response. In the contralateral hindlimbs, chondral defects were created, MAMCs were patterned in situ, and nanofracture (Nfx), a clinically utilized method to promote cartilage repair, was performed. The NFx holes enabled marrow-derived stromal cells to enter the defect area and served as repeatable bone injury sites to monitor over time. Animals were evaluated 1 and 2 weeks after injection and surgery. Analysis of injected MAMCs showed that bioactive cargo was released in a controlled fashion over 2 weeks. A bone fluorochrome label injected at the time of surgery displayed maintenance of mineral labeling in the therapeutic group, but resorption in both control groups. Alkaline phosphatase (AP) staining at the osteochondral interface revealed higher AP activity in defects treated with therapeutic MAMCs. Overall, this study develops a gravity-based approach to pattern bioactive factors along the osteochondral interface, and applies this novel biofabrication strategy to preserve bone structure after osteochondral injury.
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影响因子：
7.2
作者：
Albro MB;Bergholt MS;St-Pierre JP;Vinals Guitart A;Zlotnick HM;Evita EG;Stevens MM
通讯作者：
Stevens MM
影响因子：
3.2
作者：
Jadin, KD;Wong, BL;Sah, RL
通讯作者：
Sah, RL
影响因子：
4.6
作者：
Galarraga, Jonathan H.;Kwon, Mi Y.;Burdick, Jason A.
通讯作者：
Burdick, Jason A.
影响因子：
4.1
作者：
Karl, Alexandra;Olbrich, Norman;Mueller, Michael B.
通讯作者：
Mueller, Michael B.
影响因子：
1.8
作者：
Bonadio, Marcelo B;Friedman, James M;Madry, Henning
通讯作者：
Madry, Henning