Department of Orthopedic Surgery, Columbia University, New York, NY, 10032, USA.
ACatechol, Inc., Santa Barbara, CA, 93103, USA.
Adv Healthc Mater. 2022 May;11(10):e2102344. doi: 10.1002/adhm.202102344. Epub 2022 Jan 22.
Current suture-based surgical techniques used to repair torn rotator cuff tendons do not result in mechanically competent tendon-to-bone attachments, leading to high postoperative failure rates. Although adhesives have been proposed to protect against sutures tearing through tendon during healing, no currently available adhesive meets the clinical needs of adhesive strength, biocompatibility, and promotion of healing. Here, a biocompatible, graded, 3,4-dihydroxy phenyl chitosan (BGC) bioadhesive designed to meet these needs is presented. Although 3,4-dihydroxy phenyl chitosan (DP-chitosan) bioadhesives are biocompatible, their adhesion strength is low; soluble oxidants or cross-linking agents can be added for higher bonding strength, but this sacrifices biocompatibility. These challenges are overcome by developing a periodate-modified ion exchange resin-bead filtration system that oxidizes catechol moieties to quinones and filters off the activating agent and resin. The resulting BGC bioadhesive exhibited sixfold higher strength compared to commercially available tissue adhesives, with strength in the range necessary to improve tendon-to-bone repair (≈1MPa, ≈20% of current suture repair strength). The bioadhesive is biocompatible and promoted tenogenesis; cells exposed to the bioadhesive demonstrated enhanced expression of collagen I and the tenogenic marker Scx. Results demonstrated that the bioadhesive has the potential to improve the strength of a tendon-to-bone repair and promote healing.
目前用于修复撕裂的肩袖肌腱的缝线式外科技术不能使肌腱与骨之间形成机械有效的附着,导致术后高失败率。虽然已经提出了使用粘合剂来防止在愈合过程中缝线撕裂肌腱,但目前没有可用的粘合剂能够满足粘合强度、生物相容性和促进愈合的临床需求。在这里,提出了一种生物相容性的、分级的、3,4-二羟基苯基壳聚糖(BGC)生物粘合剂,旨在满足这些需求。尽管 3,4-二羟基苯基壳聚糖(DP-壳聚糖)生物粘合剂具有生物相容性,但它们的粘合强度较低;可以添加可溶性氧化剂或交联剂以获得更高的粘合强度,但这会牺牲生物相容性。通过开发一种高碘酸盐修饰的离子交换树脂珠过滤系统克服了这些挑战,该系统将儿茶酚部分氧化为醌,并过滤掉激活剂和树脂。与市售的组织粘合剂相比,所得 BGC 生物粘合剂的强度提高了六倍,其强度范围足以改善肌腱与骨的修复(≈1MPa,约为现有缝线修复强度的 20%)。该生物粘合剂具有生物相容性并促进成腱;暴露于生物粘合剂的细胞表现出胶原 I 和腱形成标志物 Scx 的表达增强。结果表明,该生物粘合剂有可能提高肌腱与骨修复的强度并促进愈合。