Using embedded alginate microparticles to tune the properties of in situ forming poly(N-isopropylacrylamide)-graft-chondroitin sulfate bioadhesive hydrogels for replacement and repair of the nucleus pulposus of the intervertebral disc.
Using embedded alginate microparticles to tune the properties of in situ forming poly(N-isopropylacrylamide)-graft-chondroitin sulfate bioadhesive hydrogels for replacement and repair of the nucleus pulposus of the intervertebral disc.
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使用嵌入的藻酸盐微粒调节原位形成的聚（N-异丙基丙烯酰胺）-接枝-硫酸软骨素生物粘附水凝胶的性质，用于椎间盘髓核的置换和修复。
DOI：
10.1002/jsp2.1161
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发表时间：
2021-09
期刊：
影响因子：
3.7
通讯作者：
Vernengo AJ
中科院分区：
文献类型：
--
作者：
Christiani T;Mys K;Dyer K;Kadlowec J;Iftode C;Vernengo AJ
腰痛是与椎间盘退变（IVD）相关的主要公共卫生问题。退变的早期阶段的特点是中央脱水，凝胶部分的IVD，髓核（NP）。一种可能的治疗方法是在IVD退行性变的早期阶段用水凝胶代替NP，水凝胶可以恢复健康的生物力学，同时支持组织再生。本研究评估了一种基于聚（N -异丙基丙烯酰胺-接枝-硫酸软骨素）（PNIPAAM - g - CS）的新型热敏水凝胶用于NP替代。实验证明，在PNIPAAm - g - CS水溶液中加入冷冻干燥的钙交联海藻酸盐微粒（MPs）可以调节注射溶液的流变性能，以及热沉淀复合凝胶的生物粘附性和机械性能。此外，我们假设复合材料将支持包裹细胞的活力和分化。通过改变MP浓度和直径来评估结构-材料性能关系。添加高浓度（50 mg/mL）的小MPs（20±6 μm）后，PNIPAAm - g - CS的注射性能、压缩力学性能和生物粘附强度得到了最大的改善。这种PNIPAAM - g - CS和海藻酸盐MPs的结合支持脂肪来源的间充质干细胞在可溶性GDF - 6存在下向NP样表型的生存、增殖和分化。当体外植入变性猪ivd的椎间盘内腔时，该配方将压缩区和中性区刚度恢复到完整值，并抵抗侧向弯曲下的排出。总的来说，结果表明水凝胶复合材料作为支持NP再生的支架的潜力。这项工作独特地证明了再水合多糖基MPs的包封可能是一种有效的方法，可以改善原位形成水凝胶的关键功能特性，用于骨科组织工程应用。本研究评估了一种基于聚（N -异丙基丙烯酰胺-接枝-硫酸软骨素）（PNIPAAM - g - CS）的热敏水凝胶用于NP替代。在PNIPAAm - g - CS水溶液中加入冷冻干燥的钙交联海藻酸盐微颗粒（MPs），可以调节凝胶的流变学、生物粘附和生物力学性能，同时也支持被封装细胞的活力和向NP样表型的分化。这项工作独特地证明了包埋再水合多糖基MPs可能是改善原位形成水凝胶用于骨科组织工程的关键功能特性的有效方法。
Low back pain is a major public health issue associated with degeneration of the intervertebral disc (IVD). The early stages of degeneration are characterized by the dehydration of the central, gelatinous portion of the IVD, the nucleus pulposus (NP). One possible treatment approach is to replace the NP in the early stages of IVD degeneration with a hydrogel that restores healthy biomechanics while supporting tissue regeneration. The present study evaluates a novel thermosensitive hydrogel based on poly(N‐isopropylacrylamide‐graft‐chondroitin sulfate) (PNIPAAM‐g‐CS) for NP replacement. The hypothesis was tested that the addition of freeze‐dried, calcium crosslinked alginate microparticles (MPs) to aqueous solutions of PNIPAAm‐g‐CS would enable tuning of the rheological properties of the injectable solution, as well as the bioadhesive and mechanical properties of the thermally precipitated composite gel. Further, we hypothesized that the composite would support encapsulated cell viability and differentiation. Structure‐material property relationships were evaluated by varying MP concentration and diameter. The addition of high concentrations (50 mg/mL) of small MPs (20 ± 6 μm) resulted in the greatest improvement in injectability, compressive mechanical properties, and bioadhesive strength of PNIPAAm‐g‐CS. This combination of PNIPAAM‐g‐CS and alginate MPs supported the survival, proliferation, and differentiation of adipose derived mesenchymal stem cells toward an NP‐like phenotype in the presence of soluble GDF‐6. When implanted ex vivo into the intradiscal cavity of degenerated porcine IVDs, the formulation restored the compressive and neutral zone stiffnesses to intact values and resisted expulsion under lateral bending. Overall, results indicate the potential of the hydrogel composite to serve as a scaffold for supporting NP regeneration. This work uniquely demonstrates that encapsulation of re‐hydrating polysaccharide‐based MPs may be an effective method for improving key functional properties of in situ forming hydrogels for orthopedic tissue engineering applications. This work evaluates a thermosensitive hydrogel based on poly(N‐isopropylacrylamide‐graft‐chondroitin sulfate) (PNIPAAM‐g‐CS) for NP replacement. The addition of freeze‐dried, calcium crosslinked alginate microparticles (MPs) to aqueous solutions of PNIPAAm‐g‐CS enabled tuning of the rheological, bioadhesive and biomechanical properties of the gel, while also supporting encapsulated cell viability and differentiation towards an NP‐like phenotype. This work uniquely demonstrates that embedding re‐hydrating polysaccharide‐based MPs may be an effective method for improving key functional properties of in situ forming hydrogels for orthopaedic tissue engineering.
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影响因子：
16.6
作者：
Ferreira-Gonzalez S;Lu WY;Raven A;Dwyer B;Man TY;O'Duibhir E;Lewis PJS;Campana L;Kendall TJ;Bird TG;Tarrats N;Acosta JC;Boulter L;Forbes SJ
通讯作者：
Forbes SJ
影响因子：
14
作者：
Bowles RD;Setton LA
通讯作者：
Setton LA
影响因子：
4.9
作者：
Clarke LE;McConnell JC;Sherratt MJ;Derby B;Richardson SM;Hoyland JA
通讯作者：
Hoyland JA
影响因子：
3.6
作者：
Cho, Wan Jin;Oh, Se Heang;Lee, Jin Ho
通讯作者：
Lee, Jin Ho
影响因子：
4.1
作者：
Guterl, Clare C.;Torre, Olivia M.;Iatridis, James C.
通讯作者：
Iatridis, James C.