Thornton Amanda J, Alsberg Eben, Albertelli Megan, Mooney David J
Department of Biologic and Materials Sciences, University of Michigan, 1011 N. University Avenue, Ann Arbor, MI 48109-1078, USA.
Transplantation. 2004 Jun 27;77(12):1798-803. doi: 10.1097/01.tp.0000131152.71117.0e.
Minimally invasive surgical procedures are increasingly important in medicine, but biomaterials consistent with this delivery approach that allow one to control the structure of the material after implantation are lacking. Biomaterials with shape-memorizing properties could permit minimally invasive delivery of cell transplantation constructs and enable the formation of new tissues or structures in vivo in desired shapes and sizes.
Macroporous alginate hydrogel scaffolds were prepared in a number of predefined geometries, compressed into significantly smaller, different "temporary" forms, and introduced into immunocompromised mice by means of minimally invasive surgical delivery through a small catheter. Scaffolds were rehydrated in situ with a suspension of cells (primary bovine articular chondrocytes) or cell-free medium and delivered through the same catheter. Specimens were harvested at 1 hr to evaluate the efficacy of cell delivery and the recovery of scaffold geometry, and at 8 and 24 weeks to evaluate neotissue formation.
A high percentage (88%) of scaffolds that were introduced with a catheter and rehydrated with cells had recovered their original shape and size within 1 hr. This delivery procedure resulted in cartilage structures with the geometry of the original scaffold by 2 months and histologically mature appearing tissue at 6 months.
Shaped hydrogels, formed by covalently cross-linking, can be structurally collapsed into smaller, temporary shapes that permit their minimally invasive delivery in vivo. The rapid recovery of scaffold properties facilitates efficient cell seeding in vivo and permits neotissue formation in desired geometries.
微创手术在医学中日益重要,但缺乏与这种递送方式相符且能让人在植入后控制材料结构的生物材料。具有形状记忆特性的生物材料可实现细胞移植构建体的微创递送,并能在体内形成所需形状和大小的新组织或结构。
制备了多种预定义几何形状的大孔藻酸盐水凝胶支架,将其压缩成明显更小的不同“临时”形状,通过小导管经微创外科手术递送至免疫受损小鼠体内。支架在原位用细胞(原代牛关节软骨细胞)悬液或无细胞培养基复水,并通过同一导管递送。在1小时时采集样本以评估细胞递送效果和支架几何形状的恢复情况,在8周和24周时采集样本以评估新组织形成情况。
通过导管引入并用细胞复水的支架中,有高比例(88%)在1小时内恢复了其原始形状和大小。这种递送程序在2个月时形成了具有原始支架几何形状的软骨结构,在6个月时形成了组织学上成熟的组织。
通过共价交联形成的成型水凝胶可在结构上坍塌成更小的临时形状,从而允许其在体内进行微创递送。支架特性的快速恢复有助于在体内高效接种细胞,并允许形成所需几何形状的新组织。