Maruyama Masahiro, Pan Chi-Chun, Moeinzadeh Seyedsina, Storaci Hunter W, Guzman Roberto Alfonso, Lui Elaine, Ueno Masaya, Utsunomiya Takeshi, Zhang Ning, Rhee Claire, Yao Zhenyu, Takagi Michiaki, Goodman Stuart B, Yang Yunzhi Peter
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Department of Mechanical Engineering, Stanford University School of Engineering, Stanford, CA, USA.
J Orthop Translat. 2021 Mar 16;28:90-99. doi: 10.1016/j.jot.2021.01.002. eCollection 2021 May.
Background/Objective: Core decompression (CD) with scaffold and cell-based therapies is a promising strategy for providing both mechanical support and regeneration of the osteonecrotic area for early stage osteonecrosis of the femoral head (ONFH). We designed a new 3D printed porous functionally-graded scaffold (FGS) with a central channel to facilitate delivery of transplanted cells in a hydrogel to the osteonecrotic area. However, the optimal porous structural design for the FGS for the engineering of bone in ONFH has not been elucidated. The aim of this study was to fabricate and evaluate two different porous structures (30% or 60% porosity) of the FGSs in corticosteroid-associated ONFH in rabbits.
Two different FGSs with 30% or 60% porosity containing a 1-mm central channel were 3D printed using polycaprolactone and β-tricalcium phosphate. The FGS was 3-mm diameter and 32-mm length and was composed of three segments: 1-mm in length for the non-porous proximal segment, 22-mm in length for the porous (30% versus 60%) middle segment, and 9-mm in length for the 15% porous distal segment. Eighteen male New Zealand White rabbits were given a single dose of 20 mg/kg methylprednisolone acetate intramuscularly. Four weeks later, rabbits were divided into three groups: the CD group, the 30% porosity FGS group, and the 60% porosity FGS group. In the CD group, a 3-mm diameter drill hole was created into the left femoral head. In the FGS groups, a 30% or 60% porosity implant was inserted into the bone tunnel. Eight weeks postoperatively, femurs were harvested and microCT, mechanical, and histological analyses were performed.
The actual porosity and pore size of the middle segments were 26.4% ± 2.3% and 699 ± 56 μm in the 30% porosity FGS, and 56.0% ± 4.5% and 999 ± 71 μm in the 60% porosity FGS, respectively using microCT analysis. Bone ingrowth ratio in the 30% porosity FGS group was 73.9% ± 15.8%, which was significantly higher than 39.5% ± 13.0% in the CD group on microCT (p < 0.05). Bone ingrowth ratio in the 60% porosity FGS group (61.3% ± 30.1%) showed no significant differences compared to the other two groups. The stiffness at the bone tunnel site in the 30% porosity FGS group was 582.4 ± 192.3 N/mm, which was significantly higher than 338.7 ± 164.6 N/mm in the 60% porosity FGS group during push-out testing (p < 0.05). Hematoxylin and eosin staining exhibited thick and mature trabecular bone around the porous FGS in the 30% porosity FGS group, whereas thinner, more immature trabecular bone was seen around the porous FGS in the 60% porosity FGS group.
These findings indicate that the 30% porosity FGS may enhance bone regeneration and have superior biomechanical properties in the bone tunnel after CD in ONFH, compared to the 60% porosity FGS.
The translational potential of this article: This FGS implant holds promise for improving outcomes of CD for early stage ONFH.
背景/目的:采用支架和基于细胞的疗法进行髓芯减压(CD)是一种有前景的策略,可为早期股骨头坏死(ONFH)的骨坏死区域提供机械支撑并促进其再生。我们设计了一种新型的3D打印多孔功能梯度支架(FGS),其带有一个中央通道,便于将水凝胶中的移植细胞输送至骨坏死区域。然而,用于ONFH骨工程的FGS的最佳多孔结构设计尚未阐明。本研究的目的是制备并评估兔糖皮质激素相关性ONFH中两种不同多孔结构(孔隙率30%或60%)的FGS。
使用聚己内酯和β-磷酸三钙3D打印两种不同的FGS,孔隙率分别为30%或60%,并带有一个1毫米宽的中央通道。FGS直径为3毫米,长度为32毫米,由三个部分组成:无孔近端部分长1毫米,多孔(30%对60%)中间部分长22毫米,15%多孔远端部分长9毫米。18只雄性新西兰白兔肌肉注射单剂量20毫克/千克醋酸甲基泼尼松龙。四周后,将兔子分为三组:CD组、孔隙率30%的FGS组和孔隙率60%的FGS组。在CD组中,在左侧股骨头钻一个直径3毫米的孔。在FGS组中,将孔隙率为30%或60%的植入物插入骨隧道。术后八周,采集股骨并进行显微CT、力学和组织学分析。
使用显微CT分析,孔隙率30%的FGS中间部分的实际孔隙率和孔径分别为26.4%±2.3%和699±56微米,孔隙率60%的FGS中间部分的实际孔隙率和孔径分别为56.0%±4.5%和999±71微米。孔隙率30%的FGS组的骨长入率为73.9%±15.8%,在显微CT上显著高于CD组的39.5%±13.0%(p<0.05)。孔隙率60%的FGS组的骨长入率(61.3%±30.1%)与其他两组相比无显著差异。在推出试验中,孔隙率30%的FGS组骨隧道部位的刚度为582.4±192.3牛/毫米,显著高于孔隙率60%的FGS组的338.7±164.6牛/毫米(p<0.05)。苏木精和伊红染色显示,孔隙率30%的FGS组多孔FGS周围有厚且成熟的小梁骨,而孔隙率60%的FGS组多孔FGS周围可见较薄、较不成熟的小梁骨。
这些发现表明,与孔隙率60%的FGS相比,孔隙率30%的FGS在ONFH的CD术后可能增强骨再生并在骨隧道中具有更好的生物力学性能。
本文的翻译潜力:这种FGS植入物有望改善早期ONFH的CD治疗效果。