Mechanical and Chemical Stability of Injection-Molded Microcantilevers Used for Sensing

Ultraviolet-ozone treatment is used as a standard surface cleaning procedure for removal of molecular organic contamination from analytical and sensing devices. Here, it is applied for injection-molded polymer microcantilevers before characterization and sensing experiments. This article examines the effects of the surface cleaning process using commercial equipment, in particular on the performance and mechanical properties of the cantilevers. It can be shown that the first chemical aging process essentially consist of the cross linking of the polymer chains together with a physical aging of the material. For longer exposure, the expected thermo-oxidative formation of carbonyl groups sets in and an exposure dependent chemical degradation can be detected. A process time of 20 min was found suitable as a trade-off between cleaning and stability

Numerical model of the human cornea based on stromal microstructure: identification of mechanical properties for two age groups

The optical quality of the human eye mainly depends on the refractive performance of the cornea. The shape of the cornea is a mechanical balance between intraocular pressure and tissue intrinsic stiffness. Several surgical procedures in ophthalmology alter the biomechanics of the cornea to provoke local or global curvature changes for vision correction. Legitimated by the large number of surgical interventions performed every day, the demand for a deeper understanding of corneal biomechanics is rising to improve the safety of procedures and medical devices. The aim of our work is to propose a numerical model of corneal biomechanics, based on the stromal microstructure. Our novel anisotropic constitutive material law features a probabilistic weighting approach to model collagen fiber distribution as observed on human cornea by Xray scattering analysis (Aghamohammadzadeh et. al., Structure, February 2004). Furthermore, collagen cross-linking was explicitly included in the strain energy function. Results showed that the proposed model is able to successfully reproduce both inflation and extensiometry experimental data (Elsheikh et. al., Curr Eye Res, 2007; Elsheikh et. al., Exp Eye Res, May 2008). In addition, the mechanical properties calculated for patients of different age groups (Group A: 65-79 years; Group B: 80-95 years) demonstrate an increased collagen cross-linking, and a decrease in collagen fiber elasticity from younger to older specimen. These findings correspond to what is known about maturing fibrous biological tissue. Since the presented model can handle different loading situations and includes the anisotropic distribution of collagen fibers, it has the potential to simulate clinical procedures involving nonsymmetrical tissue interventions. In the future, such mechanical model can be used to improve surgical planning and the design of next generation ophthalmic devices.

Improving chondrogenesis: potential and limitations of SOX9 gene transfer and mechanical stimulation for cartilage tissue engineering

Articular cartilage injuries and degeneration affect a large proportion of the population in developed countries world wide. Stem cells can be differentiated into chondrocytes by adding transforming growth factor-beta1 and dexamethasone to a pellet culture, which are unfeasible for tissue engineering purposes. We attempted to achieve stable chondrogenesis without any requirement for exogenous growth factors. Human mesenchymal stem cells were transduced with an adenoviral vector containing the SRY-related HMG-box gene 9 (SOX9), and were cultured in a three-dimensional (3D) hydrogel scaffold composite. As an additional treatment, mechanical stimulation was applied in a custom-made bioreactor. SOX9 increased the expression level of its known target genes, as well as its cofactors: the long form of SOX5 and SOX6. However, it was unable to increase the synthesis of sulfated glycosaminoglycans (GAGs). Mechanical stimulation slightly enhanced collagen type X and increased lubricin expression. The combination of SOX9 and mechanical load boosted GAG synthesis as shown by (35)S incorporation. GAG production rate corresponded well with the amount of (endogenous) transforming growth factor-beta1. Finally, cartilage oligomeric matrix protein expression was increased by both treatments. These findings provide insight into the mechanotransduction of mesenchymal stem cells and demonstrate the potential of a transcription factor in stem cell therapy.

Cartilage tissue engineering for degenerative joint disease

Pain in the joint is often due to cartilage degeneration and represents a serious medical problem affecting people of all ages. Although many, mostly surgical techniques, are currently employed to treat cartilage lesions, none has given satisfactory results in the long term. Recent advances in biology and material science have brought tissue engineering to the forefront of new cartilage repair techniques. The combination of autologous cells, specifically designed scaffolds, bioreactors, mechanical stimulations and growth factors together with the knowledge that underlies the principles of cell biology offers promising avenues for cartilage tissue regeneration. The present review explores basic biology mechanisms for cartilage reconstruction and summarizes the advances in the tissue engineering approaches. Furthermore, the limits of the new methods and their potential application in the osteoarthritic conditions are discussed.

Cell therapies for heart function recovery: focus on myocardial tissue engineering and nanotechnologies

Cell therapies have gained increasing interest and developed in several approaches related to the treatment of damaged myocardium. The results of multiple clinical trials have already been reported, almost exclusively involving the direct injection of stem cells. It has, however, been postulated that the efficiency of injected cells could possibly be hindered by the mechanical trauma due to the injection and their low survival in the hostile environment. It has indeed been demonstrated that cell mortality due to the injection approaches 90%. Major issues still need to be resolved and bed-to-bench followup is paramount to foster clinical implementations. The tissue engineering approach thus constitutes an attractive alternative since it provides the opportunity to deliver a large number of cells that are already organized in an extracellular matrix. Recent laboratory reports confirmed the interest of this approach and already encouraged a few groups to investigate it in clinical studies. We discuss current knowledge regarding engineered tissue for myocardial repair or replacement and in particular the recent implementation of nanotechnological approaches.

Intervertebral disc regeneration or repair with biomaterials and stem cell therapy--feasible or fiction?

The "gold standard" for treatment of intervertebral disc herniations and degenerated discs is still spinal fusion, corresponding to the saying "no disc - no pain". Mechanical prostheses, which are currently implanted, do only have medium outcome success and have relatively high re-operation rates. Here, we discuss some of the biological intervertebral disc replacement approaches, which can be subdivided into at least two classes in accordance to the two different tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). On the side of NP replacement hydrogels have been extensively tested in vitro and in vivo. However, these gels are usually a trade-off between cell biocompatibility and load-bearing capacity, hydrogels which fulfill both are still lacking. On the side of AF repair much less is known and the question of the anchoring of implants is still to be addressed. New hope for cell therapy comes from developmental biology investigations on the existence of intervertebral disc progenitor cells, which would be an ideal cell source for cell therapy. Also notochordal cells (remnants of the embryonic notochord) have been recently pushed back into focus since these cells have regenerative potential and can activate disc cells. Growth factor treatment and molecular therapies could be less problematic. The biological solutions for NP and AF replacement are still more fiction than fact. However, tissue engineering just scratched the tip of the iceberg, more satisfying solutions are yet to be added to the biomedical pipeline.

Genetic engineering and the world trade system

While the WTO agreements do not regulate the use of biotechnology per se, their rules can have a profound impact on the use of the technology for both commercial and non-commercial purposes. This book seeks to identify the challenges to international trade regulation that arise from biotechnology. The contributions examine whether existing international obligations of WTO Members are appropriate to deal with the issues arising for the use of biotechnology and whether there is a need for new international legal instruments, including a potential WTO Agreement on Biotechnology. They combine various perspectives on and topics relating to genetic engineering and trade, including human rights and gender; intellectual property rights; traditional knowledge and access and benefit sharing; food security, trade and agricultural production and food safety; and medical research, cloning and international trade.

Electrospinning Auricular Shaped Scaffolds for Tissue Engineering

Poly(ɛ)caprolactone scaffolds have been electrospun directly into an auricular shaped conductive mould. Bovine chondrocytes were harvested from articular cartilage and seeded onto 16 of the produced scaffolds, which received either an ethanol (group A) or a plasma treatment (group B) for sterilisation before seeding. The seeded scaffolds were cultured for 3 weeks in vitro and analysed with regard to total DNA and GAG content as well as the expression of AGG, COL1, COL2, MMP3 and MMP13. Rapid cell proliferation and GAG accumulation was observed until week 2. However, total DNA and GAG content decreased again in week 3. qPCR data shows a slight increase in the expression of anabolic genes and a slight decrease for the catabolic genes, with a significant difference between the groups A and B only for COL2 and MMP13.

DXA predictions of human femoral mechanical properties depend on the load configuration

The aim of this study was to evaluate the ability of dual energy X-rays absorptiometry (DXA) areal bone mineral density (aBMD) measured in different regions of the proximal part of the human femur for predicting the mechanical properties of matched proximal femora tested in two different loading configurations. 36 pairs of fresh frozen femora were DXA scanned and tested until failure in two loading configurations: a fall on the side or a one-legged standing. The ability of the DXA output from four different regions of the proximal femur in predicting the femoral mechanical properties was measured and compared for the two loading scenarios. The femoral neck DXA BMD was best correlated to the femoral ultimate force for both configurations and predicted significantly better femoral failure load (R2=0.80 vs. R2=0.66, P<0.05) when simulating a side than when simulating a standing configuration. Conversely, the work to failure was predicted similarly for both loading configurations (R2=0.54 vs. R2=0.53, P>0.05). Therefore, neck BMD should be considered as one of the key factors for discriminating femoral fracture risk in vivo. Moreover, the better predictive ability of neck BMD for femoral strength if tested in a fall compared to a one-legged stance configuration suggests that DXA's clinical relevance may not be as high for spontaneous femoral fractures than for fractures associated to a fall.

Nano-mechanical transduction of polymer micro-cantilevers to detect bio-molecular interactions

Using variothermal polymer micro-injection molding, disposable arrays of eight polymer micro-cantilevers each 500 μm long, 100 μm wide and 25 μm thick were fabricated. The present study took advantage of an easy flow grade polypropylene. After gold coating for optical read-out and asymmetrical sensitization, the arrays were introduced into the Cantisens(®) Research system to perform mechanical and functional testing. We demonstrate that polypropylene cantilevers can be used as biosensors for medical purposes in the same manner as the established silicon ones to detect single-stranded DNA sequences and metal ions in real-time. A differential signal of 7 nm was detected for the hybridization of 1 μM complementary DNA sequences. For 100 nM copper ions the differential signal was found to be (36 ± 5) nm. Nano-mechanical sensing of medically relevant, nanometer-size species is essential for fast and efficient diagnosis.