Department of Mechanical and Aerospace Engineering, Case Western Reserve University, Cleveland, OH 44106, United States.
Department of Orthopedics, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, OH 44106, United States.
Acta Biomater. 2017 Nov;63:200-209. doi: 10.1016/j.actbio.2017.09.006. Epub 2017 Sep 7.
Flexor tendon lacerations are traditionally repaired by using non-absorbable monofilament sutures. Recent investigations have explored to improve the healing process by growth factor delivery from the sutures. However, it is difficult to conjugate growth factors to nylon or other synthetic sutures. This study explores the performance of a novel electrochemically aligned collagen suture in a flexor tendon repair model with and without platelet derived growth factor following complete tendon laceration in vivo. Collagen suture was fabricated via electrochemical alignment process. Heparin was covalently bound to electrochemically aligned collagen sutures (ELAS) to facilitate affinity bound delivery of platelet-derived growth factor-BB (PDGF-BB). Complete laceration of the flexor digitorum profundus in the third digit of the foot was performed in 36 skeletally mature White Leghorn chickens. The left foot was used as the positive control. Animals were randomly divided into three groups: control specimens treated with standard nylon suture (n=12), specimens repaired with heparinated ELAS suture without PDGF-BB (n=12) and specimens repaired with heparinated ELAS suture with affinity bound PDGF-BB (n=12). Specimens were harvested at either 4weeks or 12weeks following tendon repair. Differences between groups were evaluated by the degree of gross tendon excursion, failure load/stress, stiffness/modulus, absorbed energy at failure, elongation/strain at failure. Quantitative histological scoring was performed to assess cellularity and vascularity. Closed flexion angle measurements demonstrated no significant differences in tendon excursion between the study groups at 4 or 12weeks. Biomechanical testing showed that the group treated with PDGF-BB bound heparinated ELAS suture had significantly higher stiffness and failure load (p<0.05) at 12-weeks relative to both heparinated ELAS suture and nylon suture. Similarly, the group treated with PDGF-BB bound suture had significantly higher ultimate tensile strength and Young's modulus (p<0.05) at 12-weeks relative to both ELAS suture and nylon suture. Compared to nylon controls, heparinized ELAS with PDGF-BB improved biomechanics and vascularity during tendon healing by 12-weeks following primary repair. The ability of ELAS to deliver PDGF-BB to the lacerated area of tendon presents investigators with a functional bioinductive platform to improve repair outcomes following flexor tendon repair.
A high strength aligned collagen suture was fabricated via linear electrocompaction and heparinized for prolonged delivery of PDFG-BB. When it was used to suture a complete lacerated flexor tendon in a chicken model controlled release of the PDGF-BB improved the strength of treated tendon after 12 weeks compared to tendon sutured with commercial nylon suture. Furthermore, Collagen suture with affinity bound PDGF-BB enhanced the vascularization and remodeling of lacerated tendon when it compare to synthetic nylon suture. Overall, electrocompacted collagen sutures holds potential to improve repair outcome in flexor tendon surgeries by improving repair strength and stiffness, vascularity, and remodeling via sustained delivery of the PDGF-BB. The bioinductive collagen suture introduces a platform for sustained delivery of other growth factors for a wide-array of applications.
屈肌腱裂伤传统上用不可吸收的单丝缝线修复。最近的研究探索了通过从缝线中输送生长因子来改善愈合过程。然而，将生长因子与尼龙或其他合成缝线结合起来是很困难的。本研究探讨了一种新型电化学排列胶原缝线在体内完全肌腱撕裂后的屈肌腱修复模型中的性能，以及在该模型中是否有血小板衍生生长因子（PDGF-BB）的存在。
通过电化学排列过程制备胶原缝线。肝素通过共价键结合到电化学排列的胶原缝线（ELAS）上，以促进血小板衍生生长因子-BB（PDGF-BB）的亲和结合递药。在 36 只骨骼成熟的白来航鸡的第三趾深屈肌腱完全撕裂。左脚用作阳性对照。动物随机分为三组：用标准尼龙缝线处理的对照标本（n=12）、用肝素化 ELAS 缝线修复但无 PDGF-BB 的标本（n=12）和用肝素化 ELAS 缝线修复且结合 PDGF-BB 的标本（n=12）。标本分别在肌腱修复后 4 周或 12 周时取出。通过大体肌腱位移、失效负荷/应力、刚度/模量、失效时吸收的能量、失效时的伸长/应变来评估组间差异。进行定量组织学评分以评估细胞活力和血管生成。闭合弯曲角度测量表明，在 4 周或 12 周时，研究组之间的肌腱位移没有显著差异。生物力学测试显示，在 12 周时，用 PDGF-BB 结合的肝素化 ELAS 缝线治疗的组具有显著更高的刚度和失效负荷（p<0.05），与肝素化 ELAS 缝线和尼龙缝线相比。同样，用 PDGF-BB 结合缝线治疗的组在 12 周时具有显著更高的极限拉伸强度和杨氏模量（p<0.05），与 ELAS 缝线和尼龙缝线相比。与尼龙对照相比，肝素化 ELAS 与 PDGF-BB 联合使用可在初次修复后 12 周内改善肌腱愈合的生物力学和血管生成。ELAS 能够将 PDGF-BB 递送至肌腱撕裂区域，为研究人员提供了一个功能性的生物诱导平台，以改善屈肌腱修复后的修复效果。
通过线性电压实制备了高强度的排列胶原缝线，并对其进行肝素化处理，以延长 PDFG-BB 的释放时间。当它被用于缝合鸡模型中的完全撕裂的屈肌腱时，与商业尼龙缝线缝合的肌腱相比，PDGF-BB 的控释在 12 周后提高了治疗肌腱的强度。此外，与合成尼龙缝线相比，与亲和结合 PDGF-BB 的胶原缝线增强了撕裂肌腱的血管生成和重塑。总之，通过持续输送 PDGF-BB，电压实胶原缝线在改善修复强度和刚度、血管生成和重塑方面具有改善屈肌腱手术修复效果的潜力。生物诱导胶原缝线为广泛的应用提供了一个持续输送其他生长因子的平台。
