Klabukov Ilya, Tenchurin Timur, Shepelev Alexey, Baranovskii Denis, Mamagulashvili Vissarion, Dyuzheva Tatiana, Krasilnikova Olga, Balyasin Maksim, Lyundup Alexey, Krasheninnikov Mikhail, Sulina Yana, Gomzyak Vitaly, Krasheninnikov Sergey, Buzin Alexander, Zayratyants Georgiy, Yakimova Anna, Demchenko Anna, Ivanov Sergey, Shegay Peter, Kaprin Andrey, Chvalun Sergei
Department of Regenerative Medicine, National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 249031 Obninsk, Russia.
Department of Urology and Operative Nephrology, Peoples Friendship University of Russia (RUDN University), 117198 Moscow, Russia.
Biomedicines. 2023 Mar 1;11(3):745. doi: 10.3390/biomedicines11030745.
This article reports the electrospinning technique for the manufacturing of multilayered scaffolds for bile duct tissue engineering based on an inner layer of polycaprolactone (PCL) and an outer layer either of a copolymer of D,L-lactide and glycolide (PLGA) or a copolymer of L-lactide and ε-caprolactone (PLCL). A study of the degradation properties of separate polymers showed that flat PCL samples exhibited the highest resistance to hydrolysis in comparison with PLGA and PLCL. Irrespective of the liquid-phase nature, no significant mass loss of PCL samples was found in 140 days of incubation. The PLCL- and PLGA-based flat samples were more prone to hydrolysis within the same period of time, which was confirmed by the increased loss of mass and a significant reduction of weight-average molecular mass. The study of the mechanical properties of developed multi-layered tubular scaffolds revealed that their strength in the longitudinal and transverse directions was comparable with the values measured for a decellularized bile duct. The strength of three-layered scaffolds declined significantly because of the active degradation of the outer layer made of PLGA. The strength of scaffolds with the PLCL outer layer deteriorated much less with time, both in the axial (-value = 0.0016) and radial (-value = 0.0022) directions. A novel method for assessment of the physiological relevance of synthetic scaffolds was developed and named the phase space approach for assessment of physiological relevance. Two-dimensional phase space (elongation modulus and tensile strength) was used for the assessment and visualization of the physiological relevance of scaffolds for bile duct bioengineering. In conclusion, the design of scaffolds for the creation of physiologically relevant tissue-engineered bile ducts should be based not only on biodegradation properties but also on the biomechanical time-related behavior of various compositions of polymers and copolymers.
本文报道了一种静电纺丝技术,用于制造基于聚己内酯(PCL)内层和外层为D,L-丙交酯与乙交酯共聚物(PLGA)或L-丙交酯与ε-己内酯共聚物(PLCL)的多层胆管组织工程支架。对单独聚合物降解特性的研究表明,与PLGA和PLCL相比,扁平PCL样品表现出最高的抗水解性。无论液相性质如何,在140天的孵育期内未发现PCL样品有明显的质量损失。基于PLCL和PLGA的扁平样品在同一时间段内更容易水解,这通过质量损失增加和重均分子量显著降低得到证实。对所开发的多层管状支架力学性能的研究表明,其纵向和横向强度与去细胞胆管测得的值相当。由于由PLGA制成的外层的活性降解,三层支架的强度显著下降。具有PLCL外层的支架强度随时间在轴向(p值 = 0.0016)和径向(p值 = 0.0022)方向上的劣化程度要小得多。开发了一种评估合成支架生理相关性的新方法,并将其命名为评估生理相关性的相空间方法。二维相空间(伸长模量和拉伸强度)用于评估和可视化胆管生物工程支架的生理相关性。总之,用于创建生理相关组织工程胆管的支架设计不仅应基于生物降解特性,还应基于聚合物和共聚物各种组成的生物力学时间相关行为。