Chamberlain Connie S, Lee Jae-Sung, Leiferman Ellen M, Maassen Nicholas X, Baer Geoffrey S, Vanderby Ray, Murphy William L
1 Department of Orthopedics and Rehabilitation, University of Wisconsin , Madison, Wisconsin.
Tissue Eng Part A. 2015 Mar;21(5-6):916-27. doi: 10.1089/ten.TEA.2014.0001. Epub 2014 Dec 11.
Tendon healing is a complex coordinated event orchestrated by numerous biologically active proteins. Unfortunately, tendons have limited regenerative potential and as a result, repair may be protracted months to years. Current treatment strategies do not offer localized delivery of biologically active proteins, which may result in reduced therapeutic efficacy. Surgical sutures coated with nanostructured minerals may provide a potentially universal tool to efficiently incorporate and deliver biologically active proteins directly to the wound. Additionally, previous reports indicated that treatment with bone morphogenetic protein-12 (BMP-12) improved tendon healing. Based on this information, we hypothesized that mineral-coated surgical sutures may be an effective platform for localized BMP-12 delivery to an injured tendon. The objective of this study was, therefore, to elucidate the healing effects of mineral-coated sutures releasing BMP-12 using a rat Achilles healing model. The effects of BMP-12-releasing sutures were also compared with standard BMP-12 delivery methods, including delivery of BMP-12 through collagen sponge or direct injection. Rat Achilles tendons were unilaterally transected and repaired using BMP-12-releasing suture (0, 0.15, 1.5, or 3.0 μg), collagen sponge (0 or 1.5 μg BMP-12), or direct injection (0 or 1.5 μg). By 14 days postinjury, repair with BMP-12-releasing sutures reduced the appearance of adhesions to the tendon and decreased total cell numbers. BMP-12 released from sutures and collagen sponge also tended to improve collagen organization when compared with BMP-12 delivered through injection. Based on these results, the release of a protein from sutures was able to elicit a biological response. Furthermore, BMP-12-releasing sutures modulated tendon healing, and the delivery method dictated the response of the healing tissue to BMP-12.
肌腱愈合是一个由多种生物活性蛋白精心协调的复杂过程。不幸的是,肌腱的再生潜力有限,因此修复过程可能会持续数月至数年。目前的治疗策略无法实现生物活性蛋白的局部递送,这可能会降低治疗效果。涂覆有纳米结构矿物质的手术缝线可能提供一种潜在的通用工具,以有效地将生物活性蛋白整合并直接递送至伤口。此外,先前的报告表明,用骨形态发生蛋白-12(BMP-12)治疗可改善肌腱愈合。基于这些信息,我们推测矿物质涂覆的手术缝线可能是将BMP-12局部递送至受伤肌腱的有效平台。因此,本研究的目的是使用大鼠跟腱愈合模型阐明释放BMP-12的矿物质涂覆缝线的愈合效果。还将释放BMP-12的缝线的效果与标准BMP-12递送方法进行了比较,包括通过胶原海绵递送BMP-12或直接注射。将大鼠跟腱单侧横断,并用释放BMP-12的缝线(0、0.15、1.5或3.0μg)、胶原海绵(0或1.5μg BMP-12)或直接注射(0或1.5μg)进行修复。在损伤后14天,用释放BMP-12的缝线进行修复可减少肌腱粘连的出现并减少总细胞数。与通过注射递送的BMP-12相比,从缝线和胶原海绵释放的BMP-12也倾向于改善胶原组织。基于这些结果,缝线释放蛋白质能够引发生物学反应。此外,释放BMP-12的缝线调节肌腱愈合,并且递送方法决定了愈合组织对BMP-12的反应。