纳晶微针的促渗透作用及安全性实验研究

目的探讨纳晶针作用于皮肤后,可在皮肤表面形成开放给药通道,从而促进外用药物经皮渗透和吸收的价值及安全性。方法 (1)扫描电镜观察纳晶针作用后在皮肤表面形成针孔的存在和闭合;(2)以0.125%荧光素钠为模型药物,在荧光显微镜下对比观察纳晶针+荧光素钠和单纯外用荧光素钠后,荧光在大鼠皮肤的分布情况。结果 (1)纳晶针可在皮肤表层形成给药通道,该通道在20 min左右即可闭合;(2)经过纳晶针处理过的大鼠皮肤可见耀眼的荧光(+++);而未经纳晶针处理的大鼠皮肤仅在角质层可见明确的线状荧光(+),其他部位可见微弱荧光(-)。结论纳晶针对外用药物有明显的促进渗透作用,且安全简便。     

Does Microwave Ablation of the Tumor Edge Allow for Joint-sparing Surgery in Patients With Osteosarcoma of the Proximal Tibia?

Background

Joint-sparing surgery of a patient’s native joint for osteosarcoma likely affords better function and comparable survival. However, it sometimes is challenging to resect a juxtaarticular osteosarcoma in a way that preserves the affected epiphysis because wide margins are necessary to minimize the risk of local recurrence. If there was a method to resect a tumor close to the joint and treat a potentially positive margin to prevent recurrence, it might allow salvage of a joint that otherwise might be lost.

Questions/purposes

We therefore asked (1) whether joint-preserving tumor resection could be performed for juxtaarticular osteosarcoma after microwave ablation of the tumor edge under navigation without leading to local recurrences, (2) what is the resulting function, and (3) what are the complications associated with this procedure.

Methods

Between 2009 and 2011, we treated 11 patients who had juxtaarticular osteosarcoma of the proximal tibia (mean age, 12 years; range, 9–16 years) with joint-preserving surgery by transepiphysis tumor resection after navigation-assisted microwave ablation of the tumor edge; they were followed a minimum of 37 months (mean, 48 months; range 37–62 months), and none was lost to followup. Patients were considered eligible for this procedure if they had a distance from the tumor edge to the articular surface between 10 to 15 mm, good chemotherapy responses, no pathologic fracture and no tumor involvement of major neurovascular structures. Allograft in combination with a vascularized fibula flap was used for segmental reconstruction. We recorded local tumor control, complications, and functional outcomes using the Musculoskeletal Tumor Society score, which ranges from 0 to 30, with higher scores indicating better function.

Results

There were no local recurrences. Major complications included osteonecrosis of part of the epiphysis in two patients and deep infection in one. The Musculoskeletal Tumor Society score ranged from 26 to 30 with a mean of 29.

Conclusions

In selected patients with osteosarcoma invading the epiphysis, navigated resection facilitates performing joint-sparing surgery, and in our small series, the adjuvant microwave ablation seemed to provide adequate local tumor control. Although more experience and longer followup are needed, this approach may make it possible to salvage more native joints when performing limb salvage for osteosarcoma.

Level of Evidence

Level IV, therapeutic study.     

Natural Polyphenols Enhance Stability of Crosslinked UHMWPE for Joint Implants

Background

Radiation-crosslinked UHMWPE has been used for joint implants since the 1990s. Postirradiation remelting enhances oxidative stability, but with some loss in strength and toughness. Vitamin E-stabilized crosslinked UHMWPE has shown improved strength and stability as compared with irradiated and remelted UHMWPE. With more active phenolic hydroxyl groups, natural polyphenols are widely used in the food and pharmaceutical industries as potent stabilizers and could be useful for oxidative stability in crosslinked UHMWPE.

Questions/purposes

We asked whether UHMWPE blended with polyphenols would (1) show higher oxidation resistance after radiation crosslinking; (2) preserve the mechanical properties of UHMWPE after accelerated aging; and (3) alter the wear resistance of radiation-crosslinked UHMWPE.

Methods

The polyphenols, gallic acid and dodecyl gallate, were blended with medical-grade UHMWPE followed by consolidation and electron beam irradiation at 100 kGy. Radiation-crosslinked virgin and vitamin E-blended UHMWPEs were used as reference materials. The UHMWPEs were aged at 120 °C in air with oxidation levels analyzed by infrared spectroscopy. Tensile (n = 5 per group) and impact (n = 3 per group) properties before and after aging as per ASTM F2003 were evaluated. The wear rates were examined by pin-on-disc testing (n = 3 per group). The data were reported as mean ± SDs. Statistical analysis was performed by using Student’s t-test for a two-tailed distribution with unequal variance for tensile and impact data obtained with n ≥ 3. A significant difference is defined with p < 0.05.

Results

The oxidation induction time of 100 kGy UHMWPE was prolonged to 144 hours with 0.05 wt% dodecyl gallate and 192 hours with 0.05 wt% gallic acid compared with 48 hours for 0.05 wt% vitamin E-blended UHMWPE. Accelerated aging of these polyphenol-blended UHMWPEs resulted in ultimate tensile strength of 50.4 ± 1.4 MPa and impact strength of 53 ± 5 kJ/m² for 100 kGy-irradiated UHMWPE with 0.05 wt% dodecyl gallate, for example, in comparison to 51.2 ± 0.7 MPa (p = 0.75) and 58 ± 5 kJ/m² (p = 0.29) before aging. The pin-on-disc wear rates of 100 kGy-irradiated UHMWPE with 0.05 wt% dodecyl gallate and 0.05 wt% gallic acid were 2.29 ± 0.31 and 1.65 ± 0.32 mg/million cycles, comparable to 1.68 ± 0.25 and 2.05 ± 0.22 mg/million cycles for 100 kGy-irradiated virgin and 0.05 wt% vitamin E-blended UHMWPE.

Conclusions

Based on the sample numbers tested in this study, polyphenols appear to effectively enhance the oxidation stability without altering the mechanical properties or pin-on-disc wear rate of radiation-crosslinked UHMWPE.

Clinical Relevance

Crosslinked UHMWPE with natural polyphenols with improved oxidative stability and low wear may find clinical application in joint implants.     

偏心髋臼旋转截骨术的生物力学机制及初步临床疗效

 目的 探讨偏心髋臼旋转截骨术治疗髋关节发育不良的生物力学机制及其初步临床疗效。方法 取6具经福尔马林防腐处理的女性尸体骨盆标本,建立髋关节生物力学模型,在模型上模拟偏心髋臼旋转截骨术。对骨盆缓慢施加连续纵向压力0~500 N,测量术前和术后载荷100、200、300、400、500 N时的股骨头承重区应变值,计算应力值。2007年7月至2014年10月应用偏心髋臼旋转截骨术治疗髋关节发育不良25例（26髋）,男6例,女19例;年龄11~57岁,平均31岁。术后以Harris髋关节评分评价髋关节功能,摄骨盆正位X线片测量头臼指数、中心边缘角（center-edge-angle,CE角）及Sharp角。结果-随着脊柱纵向压力加大,股骨头上的应力值随之增加。偏心髋臼旋转截骨术后应力值在载荷超过300 N后由上升趋势转变为下降趋势,总体呈抛物线状。100~500 N载荷下偏心髋臼旋转截骨术后的应力值与术前差异均无统计学意义。临床随访18例（19髋）,随访率72%。随访时间7~85个月,平均40个月。Harris髋关节评分由术前（64.3±7.2）分提高至末次随访时（85.6±5.3）分;头臼指数平均增加36.5%、CE角平均增加33.1°、Sharp角平均减少12.3°,与术前比较差异均有统计学意义。结论-偏心髋臼旋转截骨术具有较好的矫正髋臼畸形的能力,可增大股骨头的髋臼覆盖面和降低承重区压力。     

Dysregulated TGF‐β signaling alters bone microstructure in a mouse model of Loeys‐Dietz syndrome

Loeys‐Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular and skeletal abnormalities resembling Marfan syndrome, including a predisposition for pathologic fracture. LDS is caused by heterozygous mutations in the genes encoding transforming growth factor‐β (TGF‐β) type 1 and type 2 receptors. In this study, we characterized the skeletal phenotype of mice carrying a mutation in the TGF‐β type 2 receptor associated with severe LDS in humans. Cortical bone in LDS mice showed significantly reduced tissue area, bone area, and cortical thickness with increased eccentricity. However, no significant differences in trabecular bone volume were observed. Dynamic histomorphometry performed in calcein‐labeled mice showed decreased mineral apposition rates in cortical and trabecular bone with normal numbers of osteoblasts and osteoclasts. Mechanical testing of femurs by three‐point bending revealed reduced femoral strength and fracture resistance. In vitro, osteoblasts from LDS mice demonstrated increased mineralization with enhanced expression of osteoblast differentiation markers compared with control cells. These changes were associated with impaired TGF‐β1–induced Smad2 and Erk1/2 phosphorylation and upregulated TGF‐β1 ligand mRNA expression, compatible with G357W as a loss‐of‐function mutation in the TGF‐β type 2 receptor. Paradoxically, phosphorylated Smad2/3 in cortical osteocytes measured by immunohistochemistry was increased relative to controls, possibly suggesting the cross‐activation of TGF‐β–related receptors. The skeletal phenotype observed in the LDS mouse closely resembles the principal structural features of bone in humans with LDS and establishes this mouse as a valid in vivo model for further investigation of TGF‐β receptor signaling in bone. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1447–1454, 2015.