Electrospun PLLA Nanofiber Scaffolds and Their Use in Combination with BMP-2 for Reconstruction of Bone Defects

Introduction Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM). Materials and Methods The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5). Results PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups. Conclusion Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus

Functionalisation of PLLA nanofiber scaffolds using a possible cooperative effect between collagen type I and BMP-2: impact on growth and osteogenic differentiation of human mesenchymal stem cells

Mesenchymal stem cell differentiation of osteoblasts is triggered by a series of signaling processes including integrin and bone morphogenetic protein (BMP), which therefore act in a cooperative manner. The aim of this study was to analyze whether these processes can be remodeled in an artificial poly-(l)-lactide acid (PLLA) based nanofiber scaffold. Matrices composed of PLLA-collagen type I or BMP-2 incorporated PLLA-collagen type I were seeded with human mesenchymal stem cells (hMSC) and cultivated over a period of 22 days, either under growth or osteoinductive conditions. During the course of culture, gene expression of alkaline phosphatase (ALP), osteocalcin (OC) and collagen I (COL-I) as well as Smad5 and focal adhesion kinase (FAK), two signal transduction molecules involved in BMP-2 or integrin signaling were analyzed. Furthermore, calcium and collagen I deposition, as well as cell densities and proliferation, were determined using fluorescence microscopy. The incorporation of BMP-2 into PLLA-collagen type I nanofibers resulted in a decrease in diameter as well as pore sizes of the scaffold. Mesenchymal stem cells showed better adherence and a reduced proliferation on BMP-containing scaffolds. This was accompanied by an increase in gene expression of ALP, OC and COL-I. Furthermore the presence of BMP-2 resulted in an upregulation of FAK, while collagen had an impact on the gene expression of Smad5. Therefore these different strategies can be combined in order to enhance the osteoblast differentiation of hMSC on PLLA based nanofiber scaffold. By doing this, different signal transduction pathways seem to be up regulated

How did the latest increase in fees in England affect student enrolment and inequality?

This paper presents a first analysis of the increase of undergraduate tuition fees to £9,000 (€11.000) in English higher education in 2012. I use a semi-experimental research design to estimate the effect of the reforms, based on student enrolment data drawn from the Higher Education Statistics Agency (HESA). Taking into account possible anticipation effects of the fee increase, I find that enrolment declined by 15 % in the treated groups as a result of the tuition fee increase. This number is almost three times higher than what previous studies have found, and may represent a serious long term cost for the English economy. The decline in enrolments is particularly pronounced for students in older age groups and students from the service class and the middle class. No effect is visible for students from the working class, indicating that the reforms did not lead to a much-feared increase in class bias in higher education enrolment. The reforms also seem not to have exacerbated ethnic inequality in higher education, as all ethnic groups were negatively affected by the reforms. These results are consistent with earlier research in the United States and the United Kingdom, although they expand our understanding of student price responsiveness in other important ways. The paper argues that younger and older students face different costs and benefits. Older students may be less certain about their benefits, and therefore be more sensitive towards price increases. The strong decrease in mature learners may require a policy response, taking into account these differing incentives

Non-Anatomic Proximal Realignment for Recurrent Patellar Dislocation Does Not Sufficiently Prevent Redislocation

Several operative techniques have been described for recurrent patellar dislocation. Clinical results vary depending on the procedure and indication. The present study aimed to evaluate the clinical outcome of Insall’s proximal realignment for recurrent patellar dislocation at mid-term follow-up. Forty-five patients were reviewed with a mean follow-up period of 49 months after having undergone Insall’s procedure. Outcome measures included reports of redislocations, complications, patient-reported outcome scores (Kujala, Tegner activity scale) and subjective assessment. No statistically significant improvements (p < 0.05) in patient-reported outcome measures were noted. Sixteen patients (35%) had poor to fair results using the Kujala score. Subjective assessment revealed that 12 patients (27%) were dissatisfied with the outcome of their surgery and would not undergo the same procedure. Ten patients (22%) had suffered from redislocation at the latest follow-up. In 4 cases (9%), intra-articular knee hematoma occurred which required arthroscopic intervention. The overall mid-term outcome of the present study shows low patient satisfaction. Non-anatomic realignment for recurrent patellar dislocation does not adequately prevent redislocation

Inequalities in higher education in low‐ and middle‐income countries:A scoping review of the literature

Motivation:  Higher  education  is  regarded  as  a  key  instrument  to  enhance  socioeconomic  mobility  andreduce inequalities. Recent literature reviews have examined inequalities in the higher education systemsof  high-income  countries,  but  less  is  known  about  the  situation  in  low-  and  middle-income  countries,where higher education is expanding fast.Purpose:  The  article  reviews  the  academic  literature  on  higher  education  in  low-  and  middle-incomecountries using a research framework inspired by social justice and capability approaches. It considers the financial,  socio-cultural,  human,  and  political  resource  domains  on  which  people  draw,  and  how  they relate to access, participation, and outcomes in higher education.Methods: A literature search for studies explicitly discussing in-country  inequalities  in  higher  education revealed  22  publications. Substantial  knowledge  gaps remain,  especially  regarding  the  political  (and decision-making)  side  of  inequalities;  the  ideologies  and  philosophies  underpinning  higher  education systems; and the linkages between resource domains, both micro and macro.Findings:  The  review  highlights  key  elements  for  policy-makers  and  researchers:  (1)  the  financial  lens alone  is  insufficient  to  understand  and  tackle  inequalities,  since  these  are  also  shaped  by  human  and other non-financial factors; (2) socio-cultural constructs are central in explaining unequal outcomes; and (3) inequalities develop throughout one’s life and need to be considered during, but also before and afterhigher education.  The scope  of  inequalities  is  wide, and  the literature  offers a  few ideas  for short-term fixes such as part-time and online education.Policy implications: Inclusive policy frameworks for higher education should include explicit goals related to (in)equality,  which  are  best  measured in  terms  of  the  extent  to  which  certain  actions  or  choices are feasible for all. Policies in these frameworks, we argue, should go beyond providing financial support, and also address socio-cultural and human resource constraints and challenges in retention, performance, and labour market outcomes. Finally, they should consider relevant contextual determinants of inequalities.</p

Universities’ pursuit of inclusion and its effects on professional staff: the case of the United Kingdom

This paper explores the proliferation of non-academic professionals as a cultural response to universities’ mission of inclusion. Departing from a neo-institutionalist perspective, the author argues that the diffusion of highly rationalised models of institutional action shapes universities as formal organisations who engage with new levels of professional expertise in the pursuit of goals and missions. The United Kingdom (UK) offers an illustrative example, the emergence of statutory equality duties on public institutions (race equality duty 2001, disability equality duty 2006 and gender equality duty 2007) nurturing an image of universities as strategic for the pursuit of demographic inclusion. Using yearly longitudinal data on 109 UK universities from 2003 to 2011, the author shows that universities increase their professional staff in catering for demographic inclusion in terms of ethnicity and disability, revealing highly rationalised institutional responses to the aforementioned equality duties. The findings contribute to the neo-institutionalist literature drawing attention to the transformation of universities into organisational actors (i.e. highly integrated entities, strategically oriented towards the pursuit of formally articulated goals and targets), which contrasts with traditional conceptions of the university as an institution with a taken-for-granted societal role and loosely defined organisational backbone. The findings provide the impetuous for further empirical research into the role of professional staff as universities assimilate new goals and missions

Localization of spin waves in the quantum Hall ferromagnet

The topological nature of the quantized Hall plateau has a number of remarkable consequences. For the quantum Hall ferromagnet (QHF), it leads to the identification of the topological charge density of a spin distortion with the associated electrical charge density. Spin waves may couple to a scalar disorder potential via their topological density. This interaction is very similar to minimal coupling of quantum particles to a random fur. It leads to the localization of spin waves in the QHF. We derive a low-energy description of the system in terms of a nonlinear sigma-model of unitary supermatrices. A possible experimental signature of these effects in photoemission is suggested