Center for Regenerative Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
J Biomed Mater Res B Appl Biomater. 2012 Oct;100(7):1943-54. doi: 10.1002/jbm.b.32761. Epub 2012 Jul 23.
The tympanic membrane (TM), separating the external and middle ear, consists of fibrous connective tissue sandwiched between epithelial layers. To treat chronic ear infections, tympanostomy drainage tubes are placed in surgically created holes in TMs which can become chronic perforations upon extrusion. Perforations are repaired using a variety of techniques, but are limited by morbidity, unsatisfactory closure rates, or minimal regeneration of the connective tissue. A more effective, minimally-invasive therapy is necessary to enhance the perforation closure rate. Current research utilizing decellularized or alignate materials moderately enhance closure but the native TM architecture is not restored. Poly(glycerol sebacate) (PGS) is a biocompatible elastomer which supports cell migration and enzymatically degrades in contact with vascularized tissue. PGS spool-shaped plugs were manufactured using a novel process. Using minimally invasive procedures, these elastomeric plugs were inserted into chronic chinchilla TM perforations. As previously reported, effective perforation closure occurred as both flange surfaces were covered by confluent cell layers; >90% of perforations were closed at 6-week postimplantation. This unique in vivo environment has little vascularized tissue. Consequently, PGS degradation was minimal over 16-week implantation, hindering regeneration of the TM fibrous connective tissue. PGS degradation must be enhanced to promote complete TM regeneration.
鼓膜（TM）将外耳和中耳隔开，由夹在上皮层之间的纤维结缔组织组成。为了治疗慢性耳部感染，在鼓膜上通过手术制造的孔中放置鼓室造口引流管，这些孔在挤出时可能会变成慢性穿孔。使用各种技术修复穿孔，但受到发病率、不满意的闭合率或结缔组织最小再生的限制。需要更有效的、微创的治疗方法来提高穿孔闭合率。目前利用去细胞或排列材料的研究在一定程度上增强了闭合效果，但天然 TM 结构并未恢复。聚（癸二酸甘油酯）（PGS）是一种生物相容性弹性体，支持细胞迁移，并在与血管化组织接触时酶促降解。使用一种新颖的工艺制造了 PGS 螺旋形塞。使用微创程序，将这些弹性塞插入慢性南美栗鼠 TM 穿孔中。如前所述，当两个凸缘表面都被连续的细胞层覆盖时，有效穿孔闭合发生；在植入后 6 周时，超过 90%的穿孔闭合。这种独特的体内环境中几乎没有血管化组织。因此，PGS 在 16 周植入期间的降解很少，阻碍了 TM 纤维结缔组织的再生。必须增强 PGS 降解以促进 TM 完全再生。
