Advances in the Development of Gradient Scaffolds Made of Nano‑Micromaterials for Musculoskeletal Tissue Regeneration

The intricate hierarchical structure of musculoskeletal tissues,including bone and interface tissues,necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes.This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes.Building on the anatomical characteristics of bone and interfacial tissues,this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues,specifically focusing on methods used to construct compositional and structural gradients within the scaffolds.The latest applications of gradient scaffolds for the regeneration of bone,osteochondral,and tendon-to-bone interfaces are presented.Furthermore,the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed,as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.

3D Printing of Tough Hydrogel Scaffolds with Functional Surface Structures for Tissue Regeneration

Hydrogel scaffolds have numerous potential applications in the tissue engineering field.However,tough hydrogel scaffolds implanted in vivo are seldom reported because it is difficult to balance biocompatibility and high mechanical properties.Inspired by Chinese ramen,we propose a universal fabricating method(printing-P,training-T,cross-linking-C,PTC&PCT)for tough hydrogel scaffolds to fill this gap.First,3D printing fabricates a hydrogel scaffold with desired structures(P).Then,the scaffold could have extraordinarily high mechanical properties and functional surface structure by cycle mechanical training with salting-out assistance(T).Finally,the training results are fixed by photo-cross-linking processing(C).The tough gelatin hydrogel scaffolds exhibit excellent tensile strength of 6.66 MPa(622-fold untreated)and have excellent biocompatibility.Furthermore,this scaffold possesses functional surface structures from nanometer to micron to millimeter,which can efficiently induce directional cell growth.Interestingly,this strategy can produce bionic human tissue with mechanical properties of 10 kPa-10 MPa by changing the type of salt,and many hydrogels,such as gelatin and silk,could be improved with PTC or PCT strategies.Animal experiments show that this scaffold can effectively promote the new generation of muscle fibers,blood vessels,and nerves within 4 weeks,prompting the rapid regeneration of large-volume muscle loss injuries.

Application of Scaffolding Theory to Higher Vocational Students Classroom Interaction in English Teaching

Scaffolding theory is one of the mature teaching methods of constructivism model . The effective interaction between teachers and students is one characteristic of scaffold teaching. This paper aims at combining scaffolding theory with classroom interaction in teaching higher vocational students English to help students arouse interest and enhance their comprehensive ability in English learning.

Effective Teaching and Learning: Scaffolding in Reading Class

This paper explores a teaching method—scaffolding in reading class, and also studies its background theories and proposes effective plans to carry out the scaffolding method. By this cooperative teaching and learning, students can not only complete teaching activities with the help of the teacher and students themselves, but also cultivate their abilities to use English and think critically.

Smart scaffolds in bone tissue engineering: A systematic review of literature

AIM: To improve osteogenic differentiation and attachment of cells.METHODS: An electronic search was conducted inPub Med from January 2004 to December 2013. Studies which performed smart modifications on conventional bone scaffold materials were included. Scaffolds with controlled release or encapsulation of bioactive molecules were not included. Experiments which did not investigate response of cells toward the scaffold(cell attachment, proliferation or osteoblastic differentiation) were excluded. RESULTS: Among 1458 studies, 38 met the inclusion and exclusion criteria. The main scaffold varied extensively among the included studies. Smart modifications included addition of growth factors(group Ⅰ-11 studies), extracellular matrix-like molecules(group Ⅱ-13 studies) and nanoparticles(nano-HA)(group Ⅲ-17 studies). In all groups, surface coating was the most commonly applied approach for smart modification of scaffolds. In group I, bone morphogenetic proteins were mainly used as growth factor stabilized on polycaprolactone(PCL). In group Ⅱ, collagen 1 in combination with PCL, hydroxyapatite(HA) and tricalcium phosphate were the most frequent scaffolds used. In the third group, nano-HA with PCL and chitosan were used the most. As variable methods were used, a thorough and comprehensible compare between the results and approaches was unattainable.CONCLUSION: Regarding the variability in methodology of these in vitro studies it was demonstrated that smart modification of scaffolds can improve tissue properties.

The “Wrong Love” Between the Zone of Proximal Development and Scaffolding:An Interview With Prof.James P.Lantolf

The zone of proximal development(ZPD) and the scaffolding theory are very different,both in terms of their theoretical origins and connotations,and can even be said to be very different.However,during the development of the two concepts,some scholars have misunderstood them,resulting in the two being mistaken for similar concepts and therefore often confused.Professor James Lantolf from Pennsylvania State University(State College,USA) was interviewed by Professor Lili Qin from Dalian University of Foreign Studies(Dalian,China) and provides an indepth analysis of these issues.The interview begins with the theoretical roots,connotations and definitions of the ZPD and scaffolding concepts,and then unravels the story of how they have been“mistakenly loved for life”,and ultimately it is made clear that the two concepts are completely different in their practical application to language teaching and should not continue to be used interchangeably.

Restoring nervous system structure and function using tissue engineered living scaffolds

Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner- vous system injury or neurodegenerative disease. Disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regenera- tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi- neered ＂living scaffolds＂, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal dusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in predinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

Scaffolds based therapy for osteochondral lesions of the talus:A systematic review

AIM To clarify the effectiveness of scaffold-based therapy for osteochondral lesions of the talus(OLT). METHODS A systematic search of MEDLINE and EMBASE databases was performed during August 2016 and updated in January 2017. Included studies were evaluated with regard to the level of evidence(LOE) and quality of evidence(QOE) using the Modified Coleman Methodology Score. Variable reporting outcome data, clinical outcomes, and the percentage of patients who returned to sport at previous level were also evaluated. RESULTS Twenty-eight studies for a total of 897 ankles were included; 96% were either LOE Ⅲ or Ⅳ. Studies were designated as either of poor or fair quality. There were 30 treatment groups reporting six different scaffold repair techniques: 13 matrix-induced autologous chondrocyte transplantation(MACT), nine bone marrow derived cell transplantation(BMDCT), four autologous matrixinduced chondrogeneis(AMIC), and four studies of other techniques. The categories of general demographics(93%) and patient-reported outcome data(85%) were well reported. Study design(73%), imaging data(73%), clinical variables(49%), and patient history(30%) were also included. The weighted mean American Orthopaedic Foot and Ankle Society(AOFAS) score at final follow-up was: 86.7 in MACT, 88.2 in BMDCT, and 82.3 in AMIC. Eight studies reported that a weighted mean of 68.3% ofpatients returned to a previous level of sport activity. CONCLUSION Scaffold-based therapy for OLT may produce favorable clinical outcomes, but low LOE, poor QOE, and variability of the data have confounded the effectiveness of this treatment.

Novel alternative transplantation therapy for orthotopic liver transplantation in liver failure:A systematic review

BACKGROUND Orthotopic liver transplantation(OLT)is the only treatment for end-stage liver failure;however,graft shortage impedes its applicability.Therefore,studies investigating alternative therapies are plenty.Nevertheless,no study has comprehensively analyzed these therapies from different perspectives.AIM To summarize the current status of alternative transplantation therapies for OLT and to support future research.METHODS A systematic literature search was performed using PubMed,Cochrane Library and EMBASE for articles published between January 2010 and 2018,using the following MeSH terms:[(liver transplantation)AND cell]OR[(liver transplantation)AND differentiation]OR[(liver transplantation)AND organoid]OR[(liver transplantation)AND xenotransplantation].Various types of studies describing therapies to replace OLT were retrieved for full-text evaluation.Among them,we selected articles including in vivo transplantation.RESULTS A total of 89 studies were selected.There are three principle forms of treatment for liver failure:Xeno-organ transplantation,scaffold-based transplantation,and cell transplantation.Xeno-organ transplantation was covered in 14 articles,scaffold-based transplantation was discussed in 22 articles,and cell transplantation was discussed in 53 articles.Various types of alternative therapies were discussed:Organ liver,25 articles;adult hepatocytes,31 articles;fetal hepatocytes,three articles;mesenchymal stem cells(MSCs),25 articles;embryonic stem cells,one article;and induced pluripotent stem cells,three articles and other sources.Clinical applications were discussed in 12 studies:Cell transplantation using hepatocytes in four studies,five studies using umbilical cord-derived MSCs,three studies using bone marrow-derived MSCs,and two studies using hematopoietic stem cells.CONCLUSION The clinical applications are present only for cell transplantation.Scaffold-based transplantation is a comprehensive treatment combining organ and cell transplantations,which warrants future research to find relevant clinical applications.

Neuron-fibrous scaffold interfaces in the peripheral nervous system: a perspective on the structural requirements

The nerves of the peripheral nervous system are not able to effectively regenerate in cases of severe neural injury.This can result in debilitating consequences,including morbidity and lifelong impairments affecting the quality of the patient’s life.Recent findings in neural tissue engineering have opened promising avenues to apply fibrous tissue-engineered scaffolds to promote tissue regeneration and functional recovery.These scaffolds,known as neural scaffolds,are able to improve neural regeneration by playing two major roles,namely,by being a carrier for transplanted peripheral nervous system cells or biological cues and by providing structural support to direct growing nerve fibers towards the target area.However,successful implementation of scaffold-based therapeutic approaches calls for an appropriate design of the neural scaffold structure that is capable of up-and down-regulation of neuron-scaffold interactions in the extracellular matrix environment.This review discusses the main challenges that need to be addressed to develop and apply fibrous tissue-engineered scaffolds in clinical practice.It describes some promising solutions that,so far,have shown to promote neural cell adhesion and growth and a potential to repair peripheral nervous system injuries.

Customizable design ofmultiple-biomolecule delivery platform for enhanced osteogenic responses via‘tailored assembly system’

Porous titanium(Ti)scaffolds have been extensively utilized as bone substitute scaffolds due to their superior biocompatibility and excellent mechanical properties.However,naturally formed TiO2 on the surface limits fast osseointegration.Different biomolecules have been widely utilized to overcome this issue;however,homogeneous porous Ti scaffolds could not simultaneously deliver multiple biomolecules that have different release behaviors.In this study,functionally graded porous Ti scaffolds(FGPTs)with dense inner and porous outer parts were fabricated using a two-body combination and densification procedure.FGPTs with growth factor(BMP-2)and antibiotics(TCH)exhibited suitable mechanical properties as bone substituting material and presented good structural stability.The release of BMP-2 was considerably prolonged,whereas the release of TCH was comparable to that of homogenous porous titanium scaffolds(control group).The osteogenic differentiation obtained using FGPTs was maintained due to the prolonged release of BMP-2.The antimicrobial properties of these scaffolds were verified using S.aureus in terms of prior release time.In addition,various candidates for graded porous Ti scaffolds with altered pore characteristics were presented.

A Systematic Review of Animal and Clinical Studies on the Use of Scaffolds for Urethral Repair

Replacing urethral tissue with functional scaffolds has been one of the challenging problems in the field of urethra reconstruction or repair over the last several decades. Various scaffold materials have been used in animal studies, but clinical studies on use of scaffolds for urethral repair are scarce. The aim of this study was to review recent animal and clinical studies on the use of different scaffolds for urethral repair, and to evaluate these scaffolds based on the evidence from these studies. Pub Med and OVID databases were searched to identify relevant studies, in conjunction with further manual search. Studies that met the inclusion criteria were systematically evaluated. Of 555 identified studies, 38 were included for analysis. It was found that in both animal and clinical studies, scaffolds seeded with cells were used for repair of large segmental defects of the urethra, such as in tubular urethroplasty. When the defect area was small, cell-free scaffolds were more likely to be applied. A lot of pre-clinical and limited clinical evidence showed that natural or artificial materials could be used as scaffolds for urethral repair. Urinary tissue engineering is still in the immature stage, and the safety, efficacy, cost-effectiveness of the scaffolds are needed for further study.

Lexical Chunks as Scaffolding in College English Teaching

Lexical chunks minimize the language learners'burden of memorization and play a very important role in saving language pro cessing efforts so as to improve the learners'language fluency,appropriacy and idiomaticity.Lexical chunks are taken as"scaffolding"in college English teaching to effectively enhance learners'language proficiency.

Undiscovered pathology of transient scaffolding remains a driver of failures in clinical trials

AIM To statistically examine the released clinical trials and meta-analyses of polymeric bioresorbable scaffolds resuming the main accomplishments in the field with a translation to the routine clinical practice. METHODS The statistical power in clinical trials such as ABSORB Japan, ABSORB China, EVERBIO II, AIDA, and few meta-analyses by the post hoc odds ratio-based sample size calculation, and the patterns of artery remodeling published in papers from ABSORB A and B trials were evaluated. RESULTS The phenomenal admiration from the first ABSORB studies in 2006-2013 was replaced by the tremendous disappointment in 2014-2017 due to reported relatively higher rates of target lesion failure(a mean prevalence of 9.16%) and device thrombosis(2.38%) in randomized controlled trials. Otherwise, bioresorbable vascular scaffold(BVS) performs as well as the metallic drugeluting stent(DES) with a trend toward some benefits for cardiac mortality [risk ratio(RR), 0.58-0.94, P > 0.05]. The underpowered design was confirmed for some studies such as ABSORB Japan, ABSORB China, EVERBIO Ⅱ, AIDA trials, and meta-analyses of Polimeni, Collet, and Mahmoud with some unintentional bias(judged by the asymmetrical Funnel plot). Scaffold thrombosis rates with Absorb BRS were comparable with DES performed with a so-called strategy of the BVS implantation with optimized pre-dilation(P), sizing(S) and post-dilation(P)(PSP) implantation(RR, PSP vs no PSP 0.37) achieving 0.35 per 100 patient-years, which is comparable to the RR 0.49 with bare-metal stents and the RR 1.06 with everolimus DES. Both ABSORB Ⅱ and ABSORB Ⅲ trials were powered enough for a five-year follow-up, but the results were not entirely conclusive due to the mostly non-significant fashion of data. The powered metaanalyses were built mostly on statistically poor findings. CONCLUSION The misunderstanding of the pathology of transient scaffolding drives the failures of the clinical trials. More bench studies of the vascular response are required. Several next-generation BVS including multifunctional electronic scaffold grant cardiology with a huge promise to make BVS technology great again.

How to Promote Learner-Learner Scaffolding in ESL Classroom

The current study attempts to investigate learner-learner scaffolding in ESL classroom.Analyzing how learners providing scaffolding with each other,and presenting methods how to promote learner-learner scaffolding.In this paper,discourse analysis methodology utilized to carry out the research.In the study,the data collected from the transcripts of audio and video- recorded interaction during lessons in ESL classrooms at advanced level.The finding indicated that effective scaffolding among learners can promote their metacognition.It is hoped that the present study can serve to raise teachers' awareness of the importance of learner-learner scaffolding in English language teaching and learning.

The famous versus the inconvenient-or the dawn and the rise of 3D-culture systems

One of the greatest impacts on in vitro cell biology was the introduction of three-dimensional(3D)culture systems more than six decades ago and this era may be called the dawn of 3D-tissue culture.Although the advantages were obvious,this field of research was a "sleeping beauty"until the 1970s when multicellular spheroids were discovered as ideal tumor models.With this rebirth,organotypical culture systems became valu-able tools and this trend continues to increase.While in the beginning,simple approaches,such as aggregation culture techniques,were favored due to their simplicity and convenience,now more sophisticated systems are used and are still being developed.One of the boosts in the development of new culture techniques arises from elaborate manufacturing and surface modification tech-niques,especially micro and nano system technologies that have either improved dramatically or have evolved very recently.With the help of these tools,it will soon be possible to generate even more sophisticated and more organotypic-like culture systems.Since 3D per-fused or superfused systems are much more complex to set up and maintain compared to use of petri dishes and culture flasks,the added value of 3D approaches still needs to be demonstrated.

Mesenchymal stem cells in maxillary sinus augmentation: A systematic review with meta-analysis

AIM: To investigate the effectiveness of mesenchymal stem cells(MSCs) in maxillary sinus augmentation(MSA), with various scaffold materials.METHODS: MEDLINE, EMBASE and SCOPUS were searched using keywords such as sinus graft, MSA, maxillary sinus lift, sinus floor elevation, MSC and cellbased, in different combinations. The searches included full text articles written in English, published over a 10-year period(2004-2014). Inclusion criteria were clinical/radiographic and histologic/ histomorphometric studies in humans and animals, on the use of MSCs in MSA. Meta-analysis was performed only for experimental studies(randomized controlled trials and controlled trials) involving MSA, with an outcome measurement of histologic evaluation with histomorphometric analysis reported. Mean and standard deviation values of newly formed bone from each study were used, and weighted mean values were assessed to account for the difference in the number of subjects among the different studies. To compare the results between the test and the control groups, the differences of regenerated bone in mean and 95% confidence intervals were calculated.RESULTS: Thirty-nine studies(18 animal studies and 21 human studies) published over a 10-year period(between 2004 and 2014) were considered to be eligible for inclusion in the present literature review. These studies demonstrated considerable variation with respect to study type, study design, follow-up, and results. Metaanalysis was performed on 9 studies(7 animal studies and 2 human studies). The weighted mean difference estimate from a random-effect model was 9.5%(95%CI: 3.6%-15.4%), suggesting a positive effect of stem cells on bone regeneration. Heterogeneity was measured by the I2 index. The formal test confirmed the presence of substantial heterogeneity(I2 = 83%, P < 0.0001). In attempt to explain the substantial heterogeneity observed, we considered a meta-regression model with publication year, support type(animal vs humans) andfollow-up length(8 or 12 wk) as covariates. After adding publication year, support type and follow-up length to the meta-regression model, heterogeneity was no longer significant(I2 = 33%, P = 0.25).CONCLUSION: Several studies have demonstrated the potential for cell-based approaches in MSA; further clinical trials are needed to confirm these results.

Application of Gliding Scaffold System In Cable-Stayed Bridge Construction

Gonghe bridge is a double level cable-stayed concrete bridge with a single-cable-plane of single cable tower. Its span is 114+120 m and a whole length of 236 m. The gliding scaffold equipment is used for the first time in the long span cable-stayed bridge construction to reduce the construction time limit. In the process of construction, to make sure a safe connection among concrete objects with different ages, the single-supporting and single-suspension system is adopted before the concrete pouring. While the double-supporting and single-suspension system is applied after con- crete pouring. These construction systems with gliding scaffold equipment are first introduced in long span ca- ble-stayed bridge and presented in detail[1]. The practice shows that these gliding scaffold systems have many advan- tages over the traditional ones.

Discussion on Scaffolding Teaching Mode of Traditional Chinese Medicine under the Background of Internet

This study was conducted to explore the construction of scaffolding teaching mode of Traditional Chinese Medicine under the background of"Internet+".The students of Grade 2018 majoring in traditional Chinese medicine were selected as the object,and some chapters of the textbook of traditional Chinese medicine were selected and taught by the traditional teaching mode while interspersing the scaffolding teaching mode,in order to help the implementation of the scaffolding teaching model.We adopted the methods of setting up situational scaffolding,question scaffolding and guide scaffolding to carry out relevant teaching contents.The scaffolding instruction model has a good degree of participation,and to a certain extent,it stimulates students'self-consciousness and enthusiasm,and improves their ability of analyzing and solving problems and their spirit of innovation.

Novel antigen delivery systems

Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies formaking vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a nonpathogenic prokaryotic organism: the "E2 scaffold" of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus.