Surgical Revascularization Induces Angiogenesis in Orthotopic Bone Allograft

Background

Remodeling of structural bone allografts relies on adequate revascularization, which can theoretically be induced by surgical revascularization. We developed a new orthotopic animal model to determine the technical feasibility of axial arteriovenous bundle implantation and resultant angiogenesis.

Questions/purposes

We asked whether arteriovenous bundles implanted in segmental allografts would increase cortical blood flow and angiogenesis compared to nonrevascularized frozen bone allografts and contralateral femoral controls.

Methods

We performed segmental femoral allotransplantation orthotopically from 10 Brown Norway rats to 20 Lewis rats. Ten rats each received either bone allograft reconstruction alone (Group I) or allograft combined with an intramedullary saphenous arteriovenous flap (Group II). At 16 weeks, we measured cortical blood flow with the hydrogen washout method. We then quantified angiogenesis using capillary density and micro-CT vessel volume measurements.

Results

All arteriovenous bundles were patent. Group II had higher mean blood flow (0.12 mL/minute/100 g versus 0.05 mL/minute/100 g), mean capillary density (23.6% versus 2.8%), and micro-CT vessel volume (0.37 mm³ versus 0.07 mm³) than Group I. Revascularized allografts had higher capillary density than untreated contralateral femora, while vessel volume did not differ and blood flow was lower.

Conclusions

Axial surgical revascularization in orthotopic allotransplants can achieve strong angiogenesis and increases cortical bone blood flow.

Clinical Relevance

Poor allograft revascularization results in frequent complications of nonunion, infection, and late stress fracture. The presented technique of surgical revascularization could therefore offer a beneficial adjunct to clinical segmental bone allografting.

     

骨移植物再血管化与骨改建的相关研究

目的探讨骨移植物再血管化与骨改建的相互关系,并对深冻自体骨和深冻异体骨的再血管化和骨改建进行比较。方法实验动物选用纯种成年健康新西兰大白兔36只。建立兔桡骨干15 mm骨—骨膜缺损模型,于其左侧缺损区植入深冻异体骨,右侧缺损区植入深冻自体骨。于术后4、8、12、16、20、24周处死动物,进行放射学、组织学及免疫组织化学观察,并借助计算机图像分析仪进行定量分析,分别用再血管化指数(每平方毫米总骨面积内的血管数)与新骨形成面积代表再血管化和骨改建程度。结果X线片显示,与宿主骨骨性愈合时间,自体骨移植组较异体骨移植组约提早4周。对再血管化指数及新骨形成面积的计量资料相关分析表明,两者呈高度正相关(r自体=0.938 8;r异体=0.969 6)。术后8~24周自体骨移植组较异体骨移植组有较高的再血管化指数(8周时分别为1.618±0.631和1.298±0.706,24周时分别为2.943±0.847和2.790±0.944)和较多的新骨形成(8周时分别为1.988±1.614和1.563±1.700,24周时分别为6.103±2.912和5.800±2.962,P<0.05)。结论骨移植后再血管化与骨改建呈高度正相关。移植骨的再血管化对骨改建可能起重要作用,免疫排斥反应可能通过影响移植骨的再血管化而最终影响骨改建。     

大鼠左肺原位移植模型的改进

目的建立改进的大鼠左肺原位移植模型,使大鼠肺移植模型的建立更加简便、有效和稳定。方法将40只SD大鼠随机配对,采用三袖套法进行肺动、静脉的吻合,内支架进行支气管重建,建立大鼠肺移植模型。结果进行大鼠左肺原位移植正式实验20对,供肺灌注到摘取时间为15±3min,供肺完成体外套管时间为5±2min,供、受体动静脉和支气管套管吻合时间为30±3min,总手术时间63±4min。手术成功18只,手术成功率90％;失败2只,其中操作失误死亡1只,肺静脉撕裂1只。血气、病理学等检查证实成功复制了肺移植缺血再灌注模型。结论改进的大鼠左肺原位移植模型操作简便,成功率高,值得推广和应用。     

同种异体骨移植的研究进展

同种异体骨移植是目前临床广泛使用于治疗各种骨缺损和促进脊柱融合的方法。根据处理方式的不同,同种异体骨可以分为：新鲜异体骨、深冻骨、冷冻干燥骨（fresh frozen allograft, FFA）和脱钙骨基质（demineralized bone matrix, DBM）。同种异体骨与新鲜的自体骨的愈合机制有着本质不同,其主要依靠“爬行替代”实现与宿主骨的融合,因此愈合速度慢、愈合质量差,容易发生骨不连和移植骨骨折,故存在较高的失败率。而复合生长因子、复合间充质干细胞以及红骨髓等方法可以提高异体骨愈合的速度。利用组织工程的原理与方法,采用复合移植的方法使异体骨得到活化,是今后异体骨移植研究与应用的发展方向。     

Osteocyte-Driven Bone Remodeling

Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. The discovery that the inhibitor of bone formation sclerostin is primarily expressed in osteocytes in bone and downregulated by anabolic stimuli provided a mechanism by which osteocytes influence the activity of osteoblasts. Advances of the last few years provided experimental evidence demonstrating that osteocytes also participate in the recruitment of osteoclasts and the initiation of bone remodeling. Apoptotic osteocytes trigger yet-to-be-identified signals that attract osteoclast precursors to specific areas of bone, which in turn differentiate to mature, bone-resorbing osteoclasts. Osteocytes are also the source of molecules that regulate the generation and activity of osteoclasts, such as OPG and RANKL; and genetic manipulations of the mouse genome leading to loss or gain of function or to altered expression of either molecule in osteocytes markedly affect bone resorption. This review highlights these investigations and discusses how the novel concept of osteocyte-driven bone resorption and formation impacts our understanding of the mechanisms by which current therapies control bone remodeling.     

大段异体骨关节移植术后感染

目的：分析恶性肿瘤患者行异体骨关节移植术后感染的原因及处理方法。方法：８３例患者术后平均随访４１．６个月。结果：９例（１０．８％）发生感染。皮瓣坏死、血肿形成、软组织覆盖薄弱使感染危险性增高；草兰氏阳性菌最常见。结论：感染是保肢手术的严重并发症。妥善的局部处理及合理应用抗菌素是重要的预防措施。     

Structural Allograft as an Option for Treating Infected Hip Arthroplasty with Massive Bone Loss

Background  

Revision of the infected hip arthroplasty with major bone loss is difficult. Attempts to restore bone stock with structural allograft are controversial.     

Osteoclast-Derived Coupling Factors in Bone Remodeling

In the bone remodeling process that takes place throughout the skeleton at bone multicellular units, intercellular communication processes are crucial. The osteoblast lineage has long been known to program osteoclast formation and hence resorption, but the preservation of bone mass and integrity requires tight control of remodeling. This needs local controls that ensure availability of mesenchymal precursors and the provision of local signals that promote differentiation through the osteoblast lineage. Some signals can come from growth factors released from resorbed bone matrix, and there is increasing evidence that the osteoclast lineage itself produces factors that can either enhance or inhibit osteoblast differentiation and hence bone formation. A number of such factors have been identified from predominantly in vitro experiments. The coupling of bone formation to resorption is increasingly recognized as a complex, dynamic process that results from the input of many local factors of cell and matrix origin that can either promote or inhibit bone formation.     

原位心脏移植一例围手术期处理

１９９４年７月我们成功地完成了１例同种原位心脏移植，术后病人存活至今，并恢复了正常生活，现将围手术期的监测、治疗等处理作一简介，并回顾体会该病人围手术期处理与术后较顺利的可能关系，为进一步把好心脏移植病人围手术期这第一关总结经验。     

Notch Signaling and Bone Remodeling

Notch signaling plays context-dependent roles in the development and maintenance of many cell types and tissues in mammals. In the skeleton, both osteoblasts and osteoclasts require Notch signaling for proper differentiation and function, and the specific roles of Notch are dependent on the differentiation status of the cell. The recent discovery of activating NOTCH2 mutations as the cause of Hajdu-Cheney syndrome has highlighted the significance of Notch signaling in human bone physiology.     

Outcomes of Adult Orthotopic Heart Transplantation With Extended Allograft Ischemic Time

Background

Heart procurement for orthotopic heart transplant (OHT) is limited by the conventional 4 hours of ischemic time (IT). Based on a recent report from our center showing that extended IT from a young donor group is safe, we widened our geographical reach, resulting in almost 40% of our transplants having an IT > 4 hours.

Methods

We retrospectively reviewed records of adult patients who underwent OHT from January 2006 to December 2011. The primary outcome was survival, and secondary outcomes included resource utilization, end-organ dysfunction, and acute cellular rejection. Overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Secondary outcomes were compared with a combination of parametric and nonparametric statistics.

Results

A total of 323 patients underwent OHT. There was a significant difference in overall survival between the standard and extended IT groups (85.7% vs 76.4%, P = .03). There were no significant differences between the groups for secondary outcomes except a higher incidence of liver dysfunction in the extended IT group (84.9% vs 73%, P = .01). Further analysis revealed that mortality remains similar if IT is below 4 hours and between 4 and 5 hours, but begins to climb after 5 hours, driving the difference between our standard and extended IT.

Conclusions

Limited donor availability for OHT dictates alternative strategies to enlarge the donor pool. Although there is an overall increasing risk with extended IT beyond 4 hours, it may be possible to safely increase the threshold to at least 5 hours without compromising the outcomes.     

An Alternative Surgical Technique in Orthotopic Cardiac Transplantation

A bstract Forty patients underwent orthotopic cardiac transplantation at Wythenshawe Hospital between May 1991 and November 1992. Twenty patients had transplantation using an alternative technique that preserves the shape of the left atrium and leaves the right atrium intact (group A). The remaining twenty had conventional transplantation using the technique described by Lower and Shumway (group B). The patients were randomized to either the new or the conventional technique on an alternate basis. There was no mortality in group A, but two patients in group B developed right ventricular failure and died. Two patients in each group developed nodal rhythm and all four recovered sinus rhythm. Echocardiography and Doppler velocimetry at the transvalvular level confirmed normal atrial function in group A with erratic atrial contraction wave in group B. There was also slightly lower incidence of mitral and tricuspid valve regurgitation in group A than in group B. The improved atrial function in group A may play a part in the prevention of right sided failure following cardiac transplantation.     

Bone Remodeling in Acetabular Reconstruction Using a Kerboull-Type Reinforcement Device and Structural Bone-Grafting in Total Hip Arthroplasty

Background

The purpose of this study was to identify the long-term durability of the Kerboull-type reinforcement device (KT plate) in acetabular reconstruction for massive bone defects, assessing the remodeling of structural bone grafts.

Allergic Airway Hyperreactivity Increases the Risk for Corneal Allograft Rejection

Corneal allografts transplanted into hosts with allergic conjunctivitis experience an increased incidence and swifter tempo of immune rejection compared to corneal allografts transplanted to nonallergic hosts. Previous findings suggested that increased risk for rejection was not a local effect produced by an inflamed eye, but was due to perturbation of the systemic immune responses to alloantigens on the corneal allograft. We tested the hypothesis that another allergic disease, airway hyperreactivity (AHR), would also increase the risk for corneal allograft rejection. Induction of AHR with either ovalbumin (OVA) or short ragweed (SRW) extract prior to keratoplasty resulted in a steep increase in the speed and incidence of corneal allograft rejection. Delayed-type hypersensitivity (DTH) responses to corneal alloantigens were closely associated with corneal allograft rejection. However, the deleterious effect of AHR on corneal allograft survival was not reflected in a heightened magnitude of allospecific DTH, cytotoxic T lymphocyte and lymphoproliferative responses to the alloantigens on the corneal allograft. Unlike Th2-based immediate hypersensitivity, CD8⁺ T-cell-based contact hypersensitivity to oxazolone did not increase the risk for corneal allograft rejection. Thus, Th2-based allergic diseases significantly reduce the immune privilege of the corneal allograft and represent important risk factors for consideration in the atopic patient.