Thermogelling bioadhesive scaffolds for intervertebral disk tissue engineering: preliminary in vitro comparison of aldehyde-based versus alginate microparticle-mediated adhesion.

Thermogelling bioadhesive scaffolds for intervertebral disk tissue engineering: preliminary in vitro comparison of aldehyde-based versus alginate microparticle-mediated adhesion.
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DOI:
10.1016/j.actbio.2015.01.025
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发表时间:
2015-04
期刊:
影响因子:
9.7
通讯作者:
Vernengo, J.
Vernengo, J.
中科院分区:
工程技术1区
文献类型:
--
作者:
Wiltsey, C.;Christiani, T.;Williams, J.;Scaramazza, J.;Van Sciver, C.;Toomer, K.;Sheehan, J.;Branda, A.;Nitzl, A.;England, E.;Kadlowec, J.;Iftode, C.;Vernengo, J.

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身体的某些承重部分的组织工程可以依赖于支架粘附或与周围组织的整合以防止脱位。一个这样的领域是椎间盘的再生(IVD)。在这项工作中,聚(N-异丙基丙烯酰胺)(PNIPAAm)接枝硫酸软骨素(CS)(PNIPAAm-g-CS)和共混物与明胶改性的CS产生可注射的聚合物,可以形成共价键与组织接触时。然而,反应性醛基的存在可能损害包封细胞的活力。因此,将脂质体包封在共混物中,设计为在聚合物粘附到组织并达到生理温度后递送ECM衍生物明胶。这项工作是基于这样的假设,即明胶的放电将通过与凝胶内的醛官能团共价反应或“封端”来增强材料的生物相容性,所述醛官能团在接触时不参与与组织的结合。作为比较,还产生了不含CS醛且具有替代粘附介质粘膜粘附藻酸钙颗粒的制剂。与单独的PNIPAAm-g-CS相比,由PNIPAAm-g-CS和CS醛的共混物形成的凝胶表现出增加的粘合强度(p<0.05)。然而,向共混物中加入明胶负载的脂质体显著降低了粘附强度(p<0.05)。藻酸盐微粒在PNIPAAm-g-CS凝胶内的包封导致拉伸强度比PNIPAAm-g-CS与CS醛的共混物的拉伸强度增加两倍(p<0.05)。细胞相容性研究表明,含有藻酸盐颗粒的制剂表现出比含有CS醛的制剂更低的细胞毒性。总之,结果表明,由包封在PNIPAAm-g-CS中的藻酸盐微粒组成的粘合剂具有用作IVD再生支架的潜力。
Tissue engineering of certain load-bearing parts of the body can be dependent on scaffold adhesion or integration with the surrounding tissue to prevent dislocation. One such area is the regeneration of the intervertebral disc (IVD). In this work, poly(N-isopropylacrylamide) (PNIPAAm) was grafted with chondroitin sulfate (CS) (PNIPAAm-g-CS) and blended with aldehyde-modified CS to generate an injectable polymer that can form covalent bonds with tissue upon contact. However, the presence of the reactive aldehyde groups can compromise the viability of encapsulated cells. Thus, liposomes were encapsulated in the blend, designed to deliver the ECM derivative, gelatin, after the polymer has adhered to tissue and reached physiological temperature. This work is based on the hypothesis that the discharge of gelatin will enhance the biocompatibility of the material by covalently reacting with, or “end-capping”, the aldehyde functionalities within the gel that did not participate in bonding with tissue upon contact. As a comparison, formulations were also created without CS aldehyde and with an alternative adhesion mediator, mucoadhesive calcium alginate particles. Gels formed from blends of PNIPAAm-g-CS and CS aldehyde exhibited increased adhesive strength compared to PNIPAAm-g-CS alone (p<0.05). However, the addition of gelatin-loaded liposomes to the blend significantly decreased the adhesive strength (p<0.05). The encapsulation of alginate microparticles within PNIPAAm-g-CS gels caused the tensile strength to increase two-fold over that of PNIPAAm-g-CS blends with CS aldehyde (p<0.05). Cytocompatibility studies indicate that formulations containing alginate particles exhibit reduced cytotoxicity over those containing CS aldehyde. Overall, the results indicated that the adhesives composed of alginate microparticles encapsulated in PNIPAAm-g-CS have the potential to serve as a scaffold for IVD regeneration.
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