Use of bone marrow derived stem cells in trauma and orthopaedics: A review of current concepts

There is a considerable amount of interest in the futurerole of bone marrow-derived stem cells(BMDSCs) and tissue engineering techniques to manage conditions within the musculoskeletal system. Repair of soft tissue and bone defects, in the early stages of injury, may lead to a reduction in progression of symptoms. Furthermore, troublesome soft tissue injuries that are notoriously fraught with problems either in healing or function, could be augmented with such techniques. The aim of this review paper is to look at the advances in such strategies to tackle these problems and assess how BMDSCs, with the aid of growth factors and scaffolds, are being used in vitro, animal and even human models to treat problems within the field of trauma and orthopaedics. There is plenty of evidence that the results are encouraging and thus gaining momentum toward their use in human studies.

基于选择性激光熔化技术的骨缺损修复用梯度多孔钛支架的研制与表征

为提高骨缺损修复的治疗效果,设计孔隙率为78.8%、70.8%、62.6%和54.4%的梯度多孔钛支架(分别表示为P1,P2,P3和P4),并通过选择性激光熔化技术进行制备。通过模拟和实验方法研究支架的成形性、显微组织、力学性能和渗透性能。模拟结果表明,4种梯度结构的最大等效应力和渗透性分别在569.1~1469.0MPa和(21.7~54.6)×10^(−9)m^(2)范围内,并且P3和P4具有更小的最大等效应力,表明P3和P4具有更高的强度。P3和P4结构支架的显微组织为α'马氏体,屈服强度和弹性模量分别为185.3~250.8MPa和6.1~9.7GPa。相比于P3结构支架,P4结构支架展现出更高的强度和与皮质骨更加匹配的弹性模量,并且其渗透性(18.6×10^(−9)m^(2))在人体骨组织渗透性范围内。因此,具有P4结构支架有望被应用于骨科植入领域。

The role of autophagy in the treatment of osteoporosis by Chinese medicines(natural)

Osteoporosis is one of the common orthopaedic diseases,characterised by increased bone fragility due to reduced bone mass and microstructural degeneration,posing a great threat to patients’quality of life and safety.In recent years,Chinese medicine(natural)has had a unique advantage in the treatment of osteoporosis and has shown good efficacy.Autophagy is an inherent cellular survival mechanism for the removal and recycling of damaged proteins and organelles and plays an important role in maintaining the stability of the intracellular environment and organ function.Therefore,this article aims to provide a comprehensive review of these Chinese medicines(natural)for the treatment of osteoporosis through autophagy.They have been intensively studied and reported to have effects such as promoting osteogenesis and anti-bone resorption.The Chinese medicines include plants such as Cistanche deserticola,Epimedium,Curculigo orchioides Gaertn,Achyranthes bidentata Blume,Leonurus japonicus Houtt,Ginseng,Chuanxiong Rhizome,Eucommia ulmoides,Morindae Officinalis Radix,Curcuma longa,Polygoni Cuspidati Rhizoma et Radix,Anemarrhena asphodeloides Bunge,Salvia miltiorrhiza Bge and Pueraria Lobata,thus providing evidence for the use of alternative herbal therapies for the effective treatment of osteoporosis.

Cemented versus uncemented stems for revision total hip replacement:A systematic review and meta-analysis

BACKGROUND The popularity of uncemented stems in revision total hip arthroplasty(THA)has increased in the last decade.AIM To assess the outcomes of both cemented and uncemented stems after mid-term follow up.METHODS This study was performed following both the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement and the Cochrane Handbook for systematic reviews and meta-analysis guidelines.Articles were chosen irrespective of country of origin or language utilized for the article full texts.This paper included studies that reviewed revision THA for both cemented or uncemented long stems.RESULTS Three eligible studies were included in the meta-analysis.Analysis was conducted by using Review Manager version 5.3.We computed the risk ratio as a measure of the treatment effect,taking into account heterogeneity.We used random-effect models.There were no significant differences found for intraoperative periprosthetic fractures[risk ratio(RR)=1.25;95%confidence interval(CI):0.29-5.32;P=0.76],aseptic loosening(RR=2.15,95%CI:0.81-5.70;P=0.13),dislocation rate(RR=0.50;95%CI:0.10-2.47;P=0.39),or infection rate(RR=0.99,95%CI:0.82-1.19;P=0.89),between the uncemented and the cemented long stems for revision THA after mid-term follow-up.CONCLUSION This study has evaluated the mid-term outcomes of both cemented and uncemented stems at first-time revision THA.In summary,there were no significant differences in the dislocation rate,aseptic loosening,intraoperative periprosthetic fracture and infection rate between the two cohorts.

隆突性皮肤纤维肉瘤的分子遗传学研究进展

隆突性皮肤纤维肉瘤（dermatofibrosarcoma protuberans，DFSP）是一种发生于真皮低度恶性／交界性的软组织肿瘤，占全部软组织肉瘤1．0％～2．0％，约占所有肿瘤的0．1％。1924年首先由Ferrand和Darier发现，被描述为“进展性和复发性真皮纤维瘤”，

Role of nanotopography in the development of tissue engineered 3D organs and tissues using mesenchymal stem cells

Recent regenerative medicine and tissue engineering strategies(using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional(3D) organs, such as bone, skin, liver, kidney and ear,using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nanosurface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.

Analysing the outcome of surgery for chronic Achilles tendinopathy over the last 50 years

AIM: To determine an association between when the study was performed, the robustness of the study and the outcomes for insertional and non-insertional Achilles tendinopathy surgery. METHODS: We performed a systematic review in accordance with the PRISMA guidelines to assess the methodology of studies investigating the outcome of surgery in chronic Achilles tendinopathy over the last 50 years to identify any trends that would account for the variable results. The Coleman Methodology Scores were correlated with the reported percentage success rates and with the publication year to determine any trends using Pearson's correlation. RESULTS: We identified 62 studies published between 1964 and 2014 reporting on a total of 2923 surgically treated Achilles tendinopathies. The average followup time was 40 mo(range 5-204 mo), and the mean reported success rate was 83.5%(range 36%-100%). The Coleman Methodology Scores were highly reproducible(r = 0.99, P < 0.01), with a mean of 40.1(SD 18.9, range 2-79). We found a negative correlation between reported success rate and overall methodology scores(r =-0.40, P < 0.001), and a positive correlation between year of publication and overall methodology scores(r = 0.46, P < 0.001). CONCLUSION: We conclude that although the success rate of surgery for chronic Acilles tendinopathy described in the literature has fallen over the last 50 years, this is probably due to a more rigorous methodology of the studies.

Polycaprolactone-carboxymethyl cellulose composites for manufacturing porous scaffolds by material extrusion

Polycaprolactone-carboxymethyl cellulose composites have been obtained and used to print porous structures by material extrusion.The materials used contained 0,2 and 5% w/w of the carboxymethyl cellulose additive.These structures have been analyzed in terms of their morphology (including the evaluation of their porosity),mechanical properties under compression load and cell affinity.Cell affinity has been evaluated by culturing sheep mesenchymal stem cells and analyzing their viability by the Alamar Blue(R)assay at days 1,3,6 and 8.The results show that composites samples have similar values of porosity and apparent density than pure polycaprolactone ones.However,samples containing 5%w/w of carboxymethyl cellulose have micropores on the filaments due to a hindered deposition process.This characteristic affects the mechanical properties of the structures,so these ones have a mean compression modulus significantly lower than pure polycaprolactone scaffolds.However, the samples containing 2%w/w of carboxymethyl cellulose show no significant difference with the pure polycaprolactone ones in terms of their mechanical properties.Moreover,the presence of 2%w/w of additive improves cell proliferation on the surface of the porous structures.As complementary information,the flow properties of the composite materials were studied and the power law equations at 210℃ obtained,as this temperature was the 3D printing temperature.These equations can be useful for simulation and designing purposes of other manufacturing processes.

Foot and ankle history and clinical examination:A guide to everyday practice

This review summarises the key points in taking a history and performing a comprehensive clinical examination for patients with foot and/or ankle problems. It is a useful guide for residents who are preparing for their specialty exams, as well as family doctors and any other doctor who has to deal with foot and ankle problems in adults.

In vivo evaluation of additively manufacturedmulti-layered scaffold for the repair of large osteochondral defects

The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects.However,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue.In this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques.The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite system.The microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model.The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage formation.The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group.Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group.The findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.

Constrained fixed-fulcrum reverse shoulder arthroplasty improves functional outcome in epileptic patients with recurrent shoulder instability

AIM: To report the results of fixed-fulcrum fully constrained reverse shoulder arthroplasty for the treatment of recurrent shoulder instability in patients with epilepsy. METHODS: A retrospective review was conducted at a single facility. Cases were identified using a com-puterized database and all clinic notes and operative reports were reviewed. All patients with epilepsy and recurrent shoulder instability were included for study. Between July 2003 and August 2011 five shoulders in five consecutive patients with epilepsy underwent fixed-fulcrum fully constrained reverse shoulder arthroplasty for recurrent anterior shoulder instability. The mean duration of epilepsy in the cohort was 21 years(range, 5-51) and all patients suffered from grand mal seizures. RESULTS: Mean age at the time of surgery was 47 years(range, 32-64). The cohort consisted of four males and one female. Mean follow-up was 4.7 years(range, 4.3-5 years). There were no further episodes of instability, and no further stabilisation or revision procedures were performed. The mean Oxford shoulder instability score improved from 8 preoperatively(range, 5-15) to 30 postoperatively(range, 16-37)(P = 0.015) and the mean subjective shoulder value improved from 20(range, 0-50) preoperatively to 60(range, 50-70) postoperatively(P = 0.016). Mean active forward elevation improved from 71° preoperatively(range,45°-130°) to 100° postoperatively(range, 80°-90°) and mean active external rotation improved from 15° preoperatively(range, 0°-30°) to 40°(20°-70°) postoperatively. No cases of scapular notching or loosening were noted. CONCLUSION: Fixed-fulcrum fully constrained reverse shoulder arthroplasty should be considered for the treatment of recurrent shoulder instability in patients with epilepsy.

Systematic review on the use of autologous matrix-induced chondrogenesis for the repair of articular cartilage defects in patients

AIM To systematically review the results of studies looking at autologous matrix-induced chondrogenesis(AMIC) in humans. METHODS A literature search was performed, adhering to the PRISMA guidelines, to review any studies using such techniques in humans. Our initial search retrieved 297 articles listed on MEDLINE, Google Scholar, CINHal and EMBASE. From these studies, 15 studies meeting the eligibility criteria were selected and formed the basis of our systematic review.RESULTS The study designs, surgical techniques and outcome measures varied between the studies. Although all studies reported improvements in patient outcome measures, this was not necessarily correlated with magnetic resonance imaging findings. Although there were many additional procedures performed, when AMIC was performed in isolation, the results tended to peak at 24 mo before declining. CONCLUSION Although short-term studies suggest improved patient reported outcomes with a variety of scaffolds, surgical techniques and rehabilitation regimes, the literature remains equivocal on whether the defect size and location, and patient factors affect the outcome. Patientbenefit appears to be maintained in the short-tomedium term but more high level studies with extensive and robust validated outcome measures should be conducted to evaluate the medium-and long-term effect of the AMIC procedure.

Measurement of forces generated during distraction of growing-rods in early onset scoliosis

AIM: To measure the forces applied during distraction of growing-rods in early onset scoliosis(EOS), aimed at developing a motorized elongation device.METHODS: A consecutive series of measurements were carried out to analyze the forces applied by the surgeon during distraction of single growing-rods in 10 patients affected by EOS(mean age 8.3 years; range 6 to 10 years) undergoing the first distraction 6 months following implantation of the rods. For each measurement, output from the transducer of a dedicated pair of distraction calipers was recorded at zero load status and at every 1 mm of distraction, up to a maximum of 12 mm for each of the two connected rods.RESULTS: Twenty measurements were obtained showing a linear increase of the load with increasing distraction, with a mean peak force of 485 N at 12 mm distraction and a single reading over 500 N. We did not observe bone fractures or ligament disruptions during or after rod elongations. There was one case of superficial wound infection in the cohort.CONCLUSION: The safe peak force carrying capacity of a motorized device for distraction of growing-rods is 500 N.

Anthropometric method for estimating component sizes in total hip arthroplasty

BACKGROUND Preoperative templating is essential in total hip arthroplasty(THA)as it not only helps to facilitate the correct implant type and size but also determines the postoperative biomechanics.Templating is also increasingly important from a medicolegal perspective and recommended in the British Orthopaedic Association Guide to Good Practice.Although templating has become increasingly digitised,there are no simple anthropometric models to predict implant sizes in the absence of digital methods.AIM To assess the accuracy of using an easily obtainable measurement(shoe size)to predict component sizes in THA compared with digital templating.METHODS Digital radiographs from a cohort of 102 patients(40 male,62 female)who had undergone uncemented or hybrid THA at a single centre were retrospectively templated to desired cup and stem sizes using TraumaCad■.We compared the templated size to the actual size of the implant and assessed if there was any correlation with the patient’s shoe size.RESULTS Statistically significant positive correlations were observed between:shoe size and templated cup size(ρ=0.92,P<0.001);shoe size with implanted cup size(ρ=0.71,P<0.001);shoe size and templated stem size(ρ=0.87,P<0.001);and shoe size with implanted stem size(ρ=0.57,P<0.001).Templated and implanted acetabular cup sizes were positively correlated(ρ=0.76,P<0.001)and were exact in 43.1%cases;80.4% of implanted cup sizes were within 1 size(+/-2 mm)of the template and 100% within 2 sizes(+/-4 mm).Positive correlation was also demonstrated between templated and implanted femoral stem sizes(ρ=0.69,P<0.001)and were exact in 52.6% cases;92.6% were within 1 size of the template and 98% within 2 sizes.CONCLUSION This study has shown there to be a significant positive correlation between shoe size and templated size.Anthropometric measurements are easily obtainable and can be used to predict uncemented component sizes in the absence of digital methods.

Osteochondral tissue repair in osteoarthritic joints： clinical challenges and opportunities in tissue engineering

Osteoarthritis （OA）, identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA usually stems from repetitive overloading to the osteochondral （OC） unit, which could result in cartilage damage and changes in the subchondral bone, leading to mechanical instability of the joint and loss of joint function. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bone in the early stages of OA and have shown potential in restoring the joint＇s function. In this approach, the use of three-dimensional scaffolds （with or without cells） provides support for tissue growth. Commercially available OC scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, none of these scaffolds has shown satisfactory clinical results. This article reviews the OC tissue structure and the design, manufacturing and performance of current OC scaffolds in treatment of OA. The findings demonstrate the importance of biological and biomechanical fixations of OC scaffolds to the host tissue in achieving an improved cartilage fill and a hyaline-like tissue formation. Achieving a strong and stable subchondral bone support that helps the regeneration of overlying cartilage seems to be still a grand challenge for the early treatment of OA.

Substitution for In Vitro and In Vivo Tests:Computational Models from Cell Attachment to Tissue Regeneration

To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trialand-error analyses to investigate suitable product’s material,structure,mechanical properites etc.The whole process from in vivo tests to clinical trials is expensive and time-consuming.Computational model is seen as a useful analysis tool to make the product development.A series of models for simulating tissue engineering process from cell attachment to tissue regeneration are reviewed.The challenging is that models for simulating tissue engineering processes are developed separately.From cell to tissue regeneration,it would go through blood injection after moving out the defect;to cell disperse and attach on the scaffold;to proliferation,migration and differentiation;and to the final part-becoming mature tissues.This paper reviewed models that related to tissue engineering process,aiming to provide an opportunity for researchers to develop a mature model for whole tissue engineering process.This article focuses on the model analysis methods of cell adhesion,nutrient transport and cell proliferation,differentiation and migration in tissue engineering.In cell adhesion model,one of the most accurate method is to use discrete phase model to govern cell movement and use Stanton-Rutland model for simulating cell attachment.As for nutrient transport model,numerical model coupling with volume of fluid model and species transport model together is suitable for predicting nutrient transport process.For cell proliferation,differentiation and migration,finite element method with random-walk algorithm is one the most advanced way to simulate these processes.Most of the model analysis methods require further experiments to verify the accuracy and effectiveness.Due to the lack of technology to detect the rate of nutrient diffusion,there are especially few researches on model analysis methods in the area of blood coagulation.Therefore,there is still a lot of work to be done in the research of the whole process model method of tissue engineering.In the future,the numerical model would be seen as an optimal way to investigate tissue engineering products bioperformance and also enable to optimize the parameters and material types of the tissue engineering products.

Management of metal-on-metal hip implant patients: Who,when and how to revise?

The debate on how best to manage patients with metal-on-metal(MOM) hip implants continues. With over 1 million patients affected worldwide, the impact is far reaching. The majority of the aggressive failures of MOM hip implants have been dealt with by revision hip surgery, leaving patients with a much more indolent pattern of failure of devices that have been in situ for more than 10 years. The longer-term outcome for such patients remains unknown, and much debate exists on how best to manage these patients. Regulatory guidance is available but remains open to interpretation due to the lack of current evidence and long-term studies. Metal ion thresholds for concern have been suggested at 7 ppb for hip resurfacing arthroplasty and below this level for large diameter total hip arthroplasties. Soft tissue changes including pseudotumours and muscle atrophy have been shown to progress, but this is not consistent. New advanced imaging techniques are helping to diagnose complications with metal hips and the reasons for failure, however these are not widely available. This has led to some centres to tackle difficult cases through multidisciplinary collaboration, for both surgical management decisions and also follow-up decisions. We summarise current evidence and consider who is at risk, when revision should be undertaken and how patients should be managed.

The molecular profile of nerve repair: humans mirror rodents

Peripheral nerve injuries(PNI)are common following blunt or penetrating trauma and can lead to disability and chronic pain in affected individuals,with limited options available to promote regeneration and functional recovery.From animal models,it is known that the regenerative capacity of the peripheral nervous system(PNS)is heavily dependent upon the remarkable ability of Schwann cells to undergo a phenotypic shift from a supportive/myelinating/maintaining phenotype to one that encourages neural regeneration.

Effects of bionic mechanical stimulation on the properties of engineered cartilage tissue

Tissue-engineered cartilage(TEC)remains a potential alternative for the repair of articular cartilage defects.However,there has been a significant different between the properties of TEC and those of natural cartilage.Studies have shown that mechanical stimulation such as compressive load can help regulate matrix remodelling in TEC,thus affecting its biomechanical properties.However,the influences of shear induced from the tissue fluid phase have not been well studied and may play an important role in tissue regeneration especially when integrated with the compressive load.Therefore,the aim of this study was to quantitatively investigate the effects of combined loading mechanisms on TEC in vitro.A bespoke biosimulator was built to incorporate the coupled motion of compression,friction and shear.The specimens,encapsulating freshly isolated rabbit chondrocytes in a hydrogel,were cultured within the biosimulator under various mechanical stimulations for 4 weeks,and the tissue activity,matrix contents and the mechanical properties were examined.Study groups were categorized according to different mechanical stimulation combinations,including strain(5-20%at 5%intervals)and frequency(0.25 Hz,0.5 Hz,1 Hz),and the effects on tissue behaviour were investigated.During the dynamic culture process,a combined load was applied to simulate the combined effects of compression,friction and shear on articular cartilage during human movement.The results indicated that a larger strain and higher frequency were more favourable for the specimen in terms of the cell proliferation and extracellular matrix synthesis.Moreover,the combined mechanical stimulation was more beneficial to matrix remodelling than the single loading motion.However,the contribution of the combined mechanical stimulation to the engineered cartilaginous tissue matrix was not sufficient to impede biodegradation of the tissue with culture time.

Myeloid sarcoma with ulnar nerve entrapment:A case report

BACKGROUND Myeloid sarcoma(MS) is relatively rare,occurring mainly in the skin and lymph nodes,and MS invasion of the ulnar nerve is particularly unusual.The main aim of this article is to present a case of MS invading the brachial plexus,causing ulnar nerve entrapment syndrome,and to further clinical understanding of the possibility of MS invasion of peripheral nerves.CASE SUMMARY We present the case of a 46-year-old man with a 13-year history of well-treated acute nonlymphocytic leukaemia who was admitted to the hospital after presenting with numbness and pain in his left little finger.The initial diagnosis was considered a simple case of nerve entrapment disease,with magnetic resonance imaging showing slightly abnormal left brachial plexus nerve alignment with local thickening,entrapment,and high signal on compression lipid images.Due to the severity of the ulnar nerve compression,we surgically investigated and cleared the entrapment and nerve tissue hyperplasia;however,subsequent pathological biopsy results revealed evidence of MS.The patient had significant relief from his neurological symptoms,with no postoperative complications,and was referred to the haemato-oncology department for further consultation about the primary disease.This is the first report of safe treatment of ulnar nerve entrapment from MS.It is intended to inform hand surgeons that nerve entrapment may be associated with extramedullary MS,as a rare presenting feature of the disease.CONCLUSION MS invasion of the brachial plexus and surrounding tissues of the upper arm,resulting in ulnar nerve entrapment and degeneration with significant neurological pain and numbness in the little finger,is uncommon.Surgical treatment significantly relieved the patient’s nerve entrapment symptoms and prevented further neurological impairment.This case is reported to highlight the rare presenting features of MS.