State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Oral & Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China..
State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Oral & Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Mater Sci Eng C Mater Biol Appl. 2019 Aug;101:1-14. doi: 10.1016/j.msec.2019.02.108. Epub 2019 Mar 21.
Tracheal reconstruction remains a major surgical challenge, mainly owing to the scarce of resilient hollow grafts with identifiable vascular pedicle in humans. In this study, we developed a three-layer, elastomeric, trachea-like composite made of poly glycerol sebacate (PGS) and polycaprolactone (PCL), which presented appropriate resilient property, timely degradation and interconnected pores. C shape PCL rings fabricated with selective laser sintering (SLS) techniques are regularly positioned around porous PGS tubes and fixed by PCL electrospinning sheath. Such an elastomeric composite underwent host remodeling including rapid vascularization and tissue infiltration after fascia wrapping. With degrading of PGS, C rings well incorporated into growing fascia and lead to the formation of pedicled tracheal grafts, which attributes to the strong and resilient properties of generated hollow grafts thus enabled orthotopic transplantation in segmental tracheal defect. Progressive remodeling on such vascularized and mechanically stable grafts resulted in epithelium regeneration on luminal side as well as production of adequate amount of collagen and elastin, which warrantees the air passage during breathing. Future study employing large animal models more representative of human tracheal regeneration is warranted before clinical translation. Using fast degrading PGS combined with PCL rings represents a philosophical shift from the prevailing focus on tough grafts in airway reconstruction and may impact regenerative medicine in general.
气管重建仍然是一个主要的外科挑战,主要是由于人类缺乏有识别血管蒂的弹性中空移植物。在这项研究中,我们开发了一种由聚甘油 - 癸二酸酯 (PGS) 和聚己内酯 (PCL) 组成的三层弹性气管样复合材料,具有适当的弹性、及时降解和相互连通的孔。通过选择性激光烧结 (SLS) 技术制造的 C 形 PCL 环规则地定位于多孔 PGS 管周围,并通过 PCL 静电纺丝护套固定。这种弹性复合材料在筋膜包裹后经历了宿主重塑,包括快速血管化和组织浸润。随着 PGS 的降解,C 环很好地整合到生长的筋膜中,并导致有蒂气管移植物的形成,这归因于生成的中空移植物的强弹性特性,从而能够进行节段性气管缺损的原位移植。这种血管化和机械稳定的移植物的渐进重塑导致腔内侧的上皮再生以及足够量的胶原蛋白和弹性蛋白的产生,这保证了呼吸过程中的空气通道。在进行临床转化之前,需要在更能代表人类气管再生的大动物模型中进行进一步的研究。使用快速降解的 PGS 结合 PCL 环代表了从当前气道重建中对坚韧移植物的关注的哲学转变,可能会对再生医学产生普遍影响。