A novel technique using hydrophilic polymers to promote axonal fusion

The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration) has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day). When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily re-paired. Polythethylene glycol (PEG) in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.     

Immunopharmacological intervention for successful neural stem cell therapy: New perspectives in CNS neurogenesis and repair

The pharmacological support and stimulation of endogenous and transplanted neural stem cells (NSCs) is a major challenge in brain repair. Trauma to the central nervous system (CNS) results in a distinct inflammatory response caused by local and infiltrating immune cells. This makes NSC-supported regeneration difficult due to the presence of inhibitory immune factors which are upregulated around the lesion site. The continual and dual role of the neuroinflammatory response leaves it difficult to decipher upon a single modulatory strategy. Therefore, understanding the influence of cytokines upon regulation of NSC self-renewal, proliferation and differentiation is crucial when designing therapies for CNS repair. There is a plethora of partially conflicting data in vitro and in vivo on the role of cytokines in modulating the stem cell niche and the milieu around NSC transplants. This is mainly due to the pleiotropic role of many factors. In order for cell-based therapy to thrive, treatment must be phase-specific to the injury and also be personalized for each patient, i.e. taking age, sex, neuroimmune and endocrine status as well as other key parameters into consideration. In this review, we will summarize the most relevant information concerning interleukin (IL)-1, IL-4, IL-10, IL-15, IFN-γ, the neuropoietic cytokine family and TNF-α in order to extract promising therapeutic approaches for further research. We will focus on the consequences of neuroinflammation on endogenous brain stem cells and the transplantation environment, the effects of the above cytokines on NSCs, as well as immunopharmacological manipulation of the microenvironment for potential therapeutic use.     

Evaluations of guided bone regeneration in canine radius segmental defects using autologous periosteum combined with fascia lata under stable external fixation

BackgroundAlthough bone defect is one of the most common orthopaedic diseases, treatment remains a challenge and an issue of debate. Guided bone regeneration (GBR) is primarily accompanied by barrier membranes; however, optional membranes show some inherent flaws in clinical application. The purpose of this study was to observe the healing velocity and quality of repairing canine radius segmental defect using transferred autologous periosteum combined with fascia lata, which can provide better biological safety than other materials.ResultsBone union was seen in most individuals from the autologous periosteum combined with fascia lata group, within an average of 14.2 weeks. Histopathologic and SEM examinations both showed the different osteogenesis state between groups. Necropsy confirmed US findings with regard to distance of bone defects and location.ConclusionThese findings suggest that autologous periosteum combined with fascia lata is as effective as a GBR membrane, even in long tubular bone defects. With reliable biological safety, the autologous periosteum combined with fascia lata is expected to achieve increasing application in orthopaedic trauma patients.

Level of evidence

Not applicable, animal study.     

Intramembranous bone regeneration differs among common inbred mouse strains following marrow ablation

Various intact and post‐injury bone phenotypes are heritable traits. In this study, we sought to determine if intramembranous bone regeneration following marrow ablation differed among common inbred mouse strains and to identify how early the differences appear. We found a ～four‐fold difference in the regenerated bone volume 21 days after marrow ablation in females from four inbred mouse strains: FVB/N (15.7 ± 8.1%, mean and standard deviation), C3H/He (15.5 ± 4.2%), C57BL/6 (12.2 ± 5.2%), and BALB/c (4.0 ± 4.4%); with BALB/c different from FVB/N (p = 0.007) and C3H/He (p = 0.002). A second experiment showed that FVB/N compared to BALB/c mice had more regenerated bone 7 and 14 days after ablation (p < 0.001), while at 21 days FVB/N mice had a greater fraction of mineralizing surface (p = 0.008) without a difference in mineral apposition rate. Thus, differences among strains are evident early during intramembranous bone regeneration following marrow ablation and appear to be associated with differences in osteogenic cell recruitment, but not osteoblast activity. The amount of regenerating bone was not correlated with other heritable traits such as the intact bone phenotype or soft tissue wound healing, suggesting that there may be independent genetic pathways for these traits. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1374–1381, 2015.     

Wound repair during arm regeneration in the red starfish Echinaster sepositus

Starfish can regenerate entire arms following their loss by both autotomic and traumatic amputation. Although the overall regenerative process has been studied several times in different asteroid species, there is still a considerable gap of knowledge as far as the detailed aspects of the repair phase at tissue and cellular level are concerned, particularly in post‐traumatic regeneration. The present work is focused on the arm regeneration model in the Mediterranean red starfish Echinaster sepositus; to describe the early cellular mechanisms of arm regeneration following traumatic amputation, different microscopy techniques were employed. In E. sepositus, the repair phase was characterized by prompt wound healing by a syncytial network of phagocytes and re‐epithelialisation followed by a localized subepidermal oedematous area formation. Scattered and apparently undifferentiated cells, intermixed with numerous phagocytes, were frequently found in the wound area during these first stages of regeneration and extensive dedifferentiation phenomena were seen at the level of the stump, particularly in the muscle bundles. A true localized blastema did not form. Our results confirm that regeneration in asteroids mainly relies on morphallactic processes, consisting in extensive rearrangement of the existing tissues which contribute to the new tissues through cell dedifferentiation, redifferentiation, and/or migration.     

PirB抑制缺氧缺血性脑损伤新生大鼠脑组织神经再生

目的 观察缺氧缺血性脑损伤（HIBD）后新生大鼠脑组织中髓鞘抑制因子配对免疫球蛋白B（PirB）的表达变化,以及抑制PirB对缺氧缺血性神经损伤的保护作用。方法 66只新生Sprague Dawley大鼠随机分为假手术组（n=30）、HIBD组（n=30）和抗PirB抗体组（n=6）,采用结扎右侧颈总动脉和低氧（8% O2）处理3 h造模,假手术组分离右侧颈总动脉但不予结扎及缺氧处理;HIBD组在完成结扎手术及缺氧处理后,两组分别在0 h、6 h、12 h、24 h和72 h各处死6只大鼠;抗PirB抗体组在完成结扎手术及缺氧处理后即刻从脑室内注入PirB抗体,于72 h后处死。采用免疫组化、Western blot和RT-PCR方法检测HIBD后各时间点新生鼠脑组织内PirB蛋白及mRNA含量的变化,同时免疫沉淀法测定Rho激酶（ROCK）活性在HIBD 72 h后的变化以及抗PirB抗体对ROCK活性的影响。结果 PirB mRNA和蛋白均在HIBD 72 h后的新生鼠脑组织中表达升高,与HIBD后0 h比较差异均有统计学意义（均P<0.05）。HIBD后 72 h,新生鼠脑组织中ROCK蛋白活性高于假手术组和抗PirB抗体组（均P<0.05）。结论 抑制PirB可能是促进HIBD后神经再生的一个新治疗方法,而该抑制作用可能是通过Rho-ROCK信号通路产生的。     

Resorbable and nonresorbable hydroxyapatite granules as bone graft substitutes in rabbit cortical defects

Background: The use of various synthetic calcium phosphate compositions for the promotion of bone in bone defects is of potential interest because such materials may be tailor made and may bond to bone. There is yet an inadequate knowledge of the role of calcium phosphate composition and resorbability for the bone response. Purpose: The aim of the present study was to compare the ability of resorbable versus nonresorbable hydroxyapatite (HA) granules to promote new bone formation in cortical bone defects. Resorbable and nonresorbable HA granules, used as bone graft substitutes, were evaluated after 6 weeks and 3 months in the rabbit tibia. Circular defects (diameter 5.0 mm) were made in both tibias of 18 New Zealand white rabbits. The 36 defects were divided into three groups (six observations per group and time, respectively). The first group was augmented with resorbable HA granules, the second group was augmented with ceramic nonresorbable HA granules, and the third group was left without augmentation (control). The animals were killed after 6 weeks and 3 months, and the tissue was evaluated with light microscopic (LM) morphology and morphometry, scanning electron microscopy (SEM), and energy dispersive x‐ray analysis (EDX). Results: After 3 months LM morphometry revealed significantly more newly formed bone in the two HA augmented groups compared with that in the control. A close contact was found between both kinds of HA granules and new bone as viewed with light microscopy and SEM. A relatively slow degradation process was indicated by the small reduction of the total granule area in the cortical defects. However, LM observations showed a change of granule form. Pilot experiments using SEM‐EDX indicate that Ca and P contents had decreased in the resorbable HA granules between 6 weeks and 3 months. Further, a higher content of Ca and P was found in the newly formed bone close to granules, in comparison with more distant newly formed bone. Conclusions: Our results suggest that both resorbable and nonresorbable HA granules promote new bone formation in rabbit cortical defects, which does not occur in control defects.     

奥硝唑联合牙周组织再生术治疗牙周炎的有效性及安全性评价

目的 探讨奥硝唑联合牙周组织再生术治疗牙周炎的有效性及安全性。方法 选择2018年3月—2019年3月于南京大学医学院附属口腔医院接受治疗的牙周炎患者100例,随机分为再生治疗组、联合治疗组,每组50例,再生治疗组患者进行牙周组织再生治疗,联合治疗组患者使用奥硝唑联合牙周组织再生术进行治疗。对2组患者牙周相关指标牙周探诊深度（periodontal probing depth,PPD）、牙周附着水平（periodontal attachment level,PAL）、牙松动度（tooth mobility degree,MD）进行检测,对2组患者治疗前、后血清丙二醛（malondialdehyde,MDA）、超氧化物歧化酶（superoxide dismutase,SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）、白细胞介素10（interleukin-10,IL-10）、白细胞介素4（interleukin-4,IL-4）、C反应蛋白（c-reactive protein,CRP）水平及免疫球蛋白水平进行检测,对比2组患者治疗效果及并发症发生情况。采用SPSS 21.0软件包对数据进行统计学分析。结果 联合治疗组患者治疗后PPD、PAL及MD水平显著低于再生治疗组（P<0.05）;联合治疗组患者血清MDA水平显著低于再生治疗组,SOD、GSH-Px水平显著高于再生治疗组（P<0.05）;联合治疗组患者血清IgA、IgM、IgG、IgE、IL-10、IL-4、CRP水平显著低于再生治疗组（P<0.05）;联合治疗组患者治疗总有效率显著高于再生治疗组,并发症发生率显著低于再生治疗组（P<0.05）。结论 使用奥硝唑联合牙周组织再生术能显著改善牙周炎患者相关牙周指数水平,减轻患者氧化应激损伤,提升患者免疫功能,抑制炎症反应,治疗效果显著,且安全性较高。