Stem Cell Delivery With Polymer Hydrogel for Treatment of Intervertebral Disc Degeneration: From 3D Culture to Design of the Delivery Device for Minimally Invasive Therapy
Stem Cell Delivery With Polymer Hydrogel for Treatment of Intervertebral Disc Degeneration: From 3D Culture to Design of the Delivery Device for Minimally Invasive Therapy
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DOI：
10.3727/096368916x692618
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发表时间：
2016-01-01
影响因子：
3.3
通讯作者：
Liu, Yang
中科院分区：
文献类型：
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作者：
Kumar, Deepak;Lyness, Alex;Liu, Yang
髓核(NP)组织损伤会对间盘(IVD)的生物力学性能产生不利的机械应变，导致随后的椎间盘退变。一种新型的、可光固化的、可注射的合成聚合物水凝胶(PHEMA-co-APMA与PAA接枝)已经证明在低氧条件下成功地包裹和分化人间充质干细胞(HMSCs)为NP表型。在我们以前的工作中展示了有希望的结果之后，在这项研究中，我们通过对基质标记物如SOX-9、aggrecan和II型胶原的表征，进一步研究了机械刺激及其对hMSC向NP表型分化的影响。此外，我们还进行了研究，以接近注射输送装置的输送参数，该注射输送装置可以将悬浮在水凝胶中的hMSCs输送到IVD中。通过不同的针规大小注射hMSC水凝胶溶液，以确定其对注射后细胞活力和IVD组织渗透的影响。对这些数据的解释为潜在的微创注射装置的设计提供了依据，该装置可以在原位光交联之前成功地将包裹在紫外光固化聚合物中的hMSCs注射到NP中。
Nucleus pulposus (NP) tissue damage can induce detrimental mechanical strain on the biomechanical performance of intervertebral discs (IVDs), causing subsequent disc degeneration. A novel, photocurable, injectable, synthetic polymer hydrogel (pHEMA-co-APMA grafted with PAA) has already demonstrated success in encapsulating and differentiating human mesenchymal stem cells (hMSCs) toward an NP phenotype during hypoxic conditions. After demonstration of promising results in our previous work, in this study we have further investigated the inclusion of mechanical stimulation and its impact on hMSC differentiation toward an NP phenotype through the characterization of matrix markers such as SOX-9, aggrecan, and collagen II. Furthermore, investigations were undertaken in order to approximate delivery parameters for an injection delivery device, which could be used to transport hMSCs suspended in hydrogel into the IVD. hMSC-laden hydrogel solutions were injected through various needle gauge sizes in order to determine its impact on postinjection cell viability and IVD tissue penetration. Interpretation of these data informed the design of a potential minimally invasive injection device, which could successfully inject hMSCs encapsulated in a UV-curable polymer into NP, prior to photo-cross-linking in situ.