Tao Meihan, Fang Zhou, Zhu Yuting, Ju Yan, Hou Zhiguo, Fu Meimei, Lu Zhihui, Cai Daozhang, Yang Jian, Guo Jinshan
Department of Orthopedic Surgery, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, PR China.
Department of Histology and Embryology, NMPA Key Laboratory for Safety Evaluation of Cosmetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, PR China.
Bioact Mater. 2024 Jul 16;41:108-126. doi: 10.1016/j.bioactmat.2024.07.004. eCollection 2024 Nov.
Inspired by tug-of-war, a game-changing bone-tendon fixation paradigm was developed. Specifically, injectable citrate-based bioactive self-expansive and planar-fixing screw (iCSP-Scr) consisting of reactive isocyanate (NCO) terminalized citrate-based polyurethane, proanthocyanidin modified hydroxyapatite (HAp) and water (with/without porogen) was developed and administrated in the bone-tendon gap. Instead of the "point to point" tendon fixation by traditional interface screws, along with the moisture-induced crosslinking and expansion of iCSP-Scr within the confined space of the irregularly shaped bone-tendon gap, the tendon graft was evenly squeezed into the bone tunnel in a "surface to surface" manner to realize strong and stable bone-tendon fixation via physical expansion, mechanical interlocking and chemical bonding (between -NCO and the -NH, -SH groups on bone matrix). The optimized iCSP-Scr exhibited rapid crosslinking, moderate expansion rate, high porosity after crosslinking, as well as tunable elasticity and toughness. The iCSP-Scr possessed favorable biodegradability, biocompatibility, and osteoinductivity derived from citrate, PC and HAp, it was able to promote osteogenesis and new bone growth inward of bone tunnel thus further enhanced the bone/iCSP-Scr mechanical interlock, ultimately leading to stronger tendon fixation (pull-out force 106.15 ± 23.15 N) comparing to titanium screws (93.76 ± 17.89 N) after 14 weeks' ACL reconstruction in a rabbit model. The iCSP-Scr not only can be used as a self-expansive screw facilitating bone-tendon healing, but also can be expanded into other osteogenic application scenarios.
受拔河比赛的启发,一种改变游戏规则的骨-肌腱固定模式被开发出来。具体而言,开发了一种由异氰酸酯(NCO)封端的柠檬酸基聚氨酯、原花青素修饰的羟基磷灰石(HAp)和水(有/无致孔剂)组成的可注射柠檬酸盐基生物活性自膨胀平面固定螺钉(iCSP-Scr),并将其应用于骨-肌腱间隙。与传统界面螺钉的“点对点”肌腱固定方式不同,随着iCSP-Scr在不规则形状的骨-肌腱间隙的受限空间内发生水分诱导的交联和膨胀,肌腱移植物以“面到面”的方式被均匀挤压到骨隧道中,通过物理膨胀、机械互锁和化学键合(-NCO与骨基质上的-NH、-SH基团之间)实现牢固稳定的骨-肌腱固定。优化后的iCSP-Scr表现出快速交联、适度的膨胀率、交联后高孔隙率以及可调节的弹性和韧性。iCSP-Scr具有良好的生物降解性、生物相容性和源自柠檬酸盐、原花青素和羟基磷灰石的骨诱导性,它能够促进骨隧道内的成骨和新骨生长,从而进一步增强骨/iCSP-Scr的机械互锁,最终在兔模型中进行14周的前交叉韧带重建后,与钛螺钉(93.76±17.89 N)相比,实现更强的肌腱固定(拔出力106.15±23.15 N)。iCSP-Scr不仅可以作为促进骨-肌腱愈合的自膨胀螺钉使用,还可以扩展到其他成骨应用场景。