Department of Mechanical Engineering, School of Biomedical Engineering, Orthopaedic Bioengineering Research Laboratory, Colorado State University, Fort Collins, CO 80523, USA.
J Orthop Surg Res. 2008 May 27;3:20. doi: 10.1186/1749-799X-3-20.
Though used for over a century, structural bone allografts suffer from a high rate of mechanical failure due to limited graft revitalization even after extended periods in vivo. Novel strategies that aim to improve graft incorporation are lacking but necessary to improve the long-term clinical outcome of patients receiving bone allografts. The current study evaluated the effect of low-intensity pulsed ultrasound (LIPUS), a potent exogenous biophysical stimulus used clinically to accelerate the course of fresh fracture healing, and longitudinal allograft perforations (LAP) as non-invasive therapies to improve revitalization of intercalary allografts in a sheep model.
Fifteen skeletally-mature ewes were assigned to five experimental groups based on allograft type and treatment: +CTL, -CTL, LIPUS, LAP, LIPUS+LAP. The +CTL animals (n = 3) received a tibial ostectomy with immediate replacement of the resected autologous graft. The -CTL group (n = 3) received fresh frozen ovine tibial allografts. The +CTL and -CTL groups did not receive LAP or LIPUS treatments. The LIPUS treatment group (n = 3), following grafting with fresh frozen ovine tibial allografts, received ultrasound stimulation for 20 minutes/day, 5 days/week, for the duration of the healing period. The LAP treatment group (n = 3) received fresh frozen ovine allografts with 500 mum longitudinal perforations that extended 10 mm into the graft. The LIPUS+LAP treatment group (n = 3) received both LIPUS and LAP interventions. All animals were humanely euthanized four months following graft transplantation for biomechanical and histological analysis.
After four months of healing, daily LIPUS stimulation of the host-allograft junctions, alone or in combination with LAP, resulted in 30% increases in reconstruction stiffness, paralleled by significant increases (p < 0.001) in callus maturity and periosteal bridging across the host/allograft interfaces. Longitudinal perforations extending 10 mm into the proximal and distal endplates filled to varying degrees with new appositional bone and significantly accelerated revitalization of the allografts compared to controls.
The current study has demonstrated in a large animal model the potential of both LIPUS and LAP therapy to improve the degree of allograft incorporation. LAP may provide an option for increasing porosity, and thus potential in vivo osseous apposition and revitalization, without adversely affecting the structural integrity of the graft.
尽管结构性骨同种异体移植物已经使用了一个多世纪，但由于即使在体内延长时间后移植物的活力恢复也有限，因此其机械失效率仍然很高。缺乏旨在改善移植物植入的新策略，但这对于改善接受骨同种异体移植物的患者的长期临床结果是必要的。本研究评估了低强度脉冲超声（LIPUS）的效果，LIPUS 是一种临床上用于加速新鲜骨折愈合过程的有效外生源物理刺激物，以及纵向同种异体穿孔（LAP）作为非侵入性治疗方法，以改善绵羊模型中节段同种异体移植物的活力恢复。
根据同种异体移植物类型和治疗方法，将 15 只骨骼成熟的母羊分为五组：+CTL、-CTL、LIPUS、LAP、LIPUS+LAP。+CTL 动物（n=3）接受胫骨截骨术，并立即替换切除的自体移植物。-CTL 组（n=3）接受新鲜冷冻的绵羊胫骨同种异体移植物。+CTL 和-CTL 组未接受 LAP 或 LIPUS 治疗。LIPUS 治疗组（n=3）在接受新鲜冷冻的绵羊胫骨同种异体移植物移植后，每天接受 20 分钟的超声刺激，每周 5 天，持续整个愈合期。LAP 治疗组（n=3）接受了 500μm 的纵向穿孔，延伸到移植物内 10mm，共 500μm。LIPUS+LAP 治疗组（n=3）同时接受了 LIPUS 和 LAP 干预。所有动物在移植后四个月进行人道安乐死，进行生物力学和组织学分析。
在四个月的愈合后，单独或与 LAP 联合对宿主-同种异体交界处进行每日 LIPUS 刺激，导致重建刚度增加 30%，同时骨痂成熟度和骨皮质桥接的显著增加（p<0.001）跨越宿主/同种异体界面。纵向穿孔延伸到近侧和远侧终板 10mm 深度，不同程度地填充了新的附加骨，并与对照组相比显著加速了同种异体移植物的活力恢复。
本研究在大型动物模型中证明了 LIPUS 和 LAP 治疗的潜力，可改善同种异体移植物的植入程度。LAP 可以提供一种增加孔隙率的选择，从而增加体内骨附着和活力恢复的潜力，而不会对移植物的结构完整性产生不利影响。
