A new biodegradable nanocomposite based on polyhedral oligomeric silsesquioxane nanocages: cytocompatibility and investigation into electrohydrodynamic jet fabrication techniques for tissue-engineered scaffolds.

Our group has developed a non-biodegradable nanocomposite based on POSS (polyhedral oligomeric silsesquioxane) nanocages with PCU [poly(carbonate urethane)] and previous studies have shown good cell-compatibility and antithrombogenic properties. The latest biodegradable formulation is a POSS-modified poly(hexanolactone/carbonate)urethane/urea containing 80% hexanolactone (caprolactone) with the tradename UCL-NanoBio. The direct effect of the polymer on cells was investigated by seeding stem cells on to circular discs of the polymer in 24-well plates; these discs were prepared mainly by electrohydrodynamic jetting.

Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans.

Objective: Little is known about the capacity, mechanisms, or timing of growth in beta-cell mass in humans. We sought to establish if the predominant expansion of beta-cell mass in humans occurs in early childhood and if, as in rodents, this coincides with relatively abundant beta-cell replication. We also sought to establish if there is a secondary growth in beta-cell mass coincident with the accelerated somatic growth in adolescence.

Bioengineering and Bioinformatics Summer Institutes: meeting modern challenges in undergraduate summer research.

Summer undergraduate research programs in science and engineering facilitate research progress for faculty and provide a close-ended research experience for students, which can prepare them for careers in industry, medicine, and academia. However, ensuring these outcomes is a challenge when the students arrive ill-prepared for substantive research or if projects are ill-defined or impractical for a typical 10-wk summer. We describe how the new Bioengineering and Bioinformatics Summer Institutes (BBSI), developed in response to a call for proposals by the National Institutes of Health (NIH) and the National Science Foundation (NSF), provide an impetus for the enhancement of traditional undergraduate research experiences with intense didactic training in particular skills and technologies.

Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis.

Type 2 diabetes (T2DM) is characterized by insulin resistance, defective insulin secretion, loss of beta-cell mass with increased beta-cell apoptosis and islet amyloid. The islet amyloid is derived from islet amyloid polypeptide (IAPP, amylin), a protein coexpressed and cosecreted with insulin by pancreatic beta-cells. In common with other amyloidogenic proteins, IAPP has the propensity to form membrane permeant toxic oligomers.

(η-Cyclo-penta-dien-yl){[3-(2,2-dicyano-ethen-yl)bicyclo-[2.2.1]hepta-2,5-dien-2-yl]ethyn-yl}(triphenyl-phosphine)nickel(II).

The title compound, [Ni(C(5)H(5))(C(13)H(7)N(2))(C(18)H(15)P)] or (η(5)-C(5)H(5))(PPh(3))Ni-C C-C(7)H(6)-C(H)=C(CN)(2), contains an unusual disubstituted norbornadienyl (NBD) ligand containing ethynyl (-C C-) and dicyano-vinyl [-C(H)=C(CN)(2)] groups. Disorder is present in the NBD group with site occupancies of 0.636 (10) and 0.

A mathematical risk-benefit analysis of composite tissue allotransplantation.

Background: Composite tissue allotransplantation (CTA) represents a surgical technology whose risks and benefits are unclear. This is problematic for clinicians with respect to patient selection and counseling, and for policy makers in evaluating its merits. Our analysis represents a mathematical approach to risk and benefit estimation in CTA.

Does severity predict distress? The relationship between subjective and objective measures of appearance and psychological adjustment, during treatment for facial lipoatrophy.

The intuitive or lay belief that the severity of a disfiguring condition predicts psychological distress is not demonstrated in clinical practice, nor in research studies. This within group study used standardised measures repeated at six month intervals, to investigate the relationship between subjective and objective measures of appearance and psychological adjustment in 51 patients undergoing treatment for facial lipoatrophy using a synthetic filler, Newfill. Results demonstrate a dissociation between objective and subjective measures with only subjective assessment predicting psychological outcomes.

Psychological management and body image issues in facial transplantation.

Facial transplantation, although controversial, is proposed as a major advance in facial reconstructive surgery, with the first partial transplant having taken place in France in November 2005. Although the psychological impact of facial transplantation will not be understood until several procedures have been carried out, this article examines the psychological issues likely to arise with particular reference to body image. A detailed framework for anticipation and management of psychological change is proposed.

The replication of beta cells in normal physiology, in disease and for therapy.

Replication of beta cells is an important source of beta-cell expansion in early childhood. The recent linkage of type 2 diabetes with several transcription factors involved in cell cycle regulation implies that growth of the beta-cell mass in early childhood might be an important determinant of risk for type 2 diabetes. Under some circumstances, including obesity and pregnancy, the beta-cell mass is adaptively increased in adult humans.

Transplant professionals' attitudes toward facial transplantation in the United Kingdom.

Background: In November 2005, the world's first partial facial transplantation positioned this treatment at the forefront in the development of facial reconstructive techniques.

Objective: Because the procedure is dependent on donation of facial tissue, we sought to understand the attitudes and beliefs of the general public and transplant professionals toward this treatment.

Methods: This research reports the results of a survey of 170 transplant professionals sampled by means of a questionnaire generated by a focus group of transplant coordinators.

Induction of endoplasmic reticulum stress-induced beta-cell apoptosis and accumulation of polyubiquitinated proteins by human islet amyloid polypeptide.

The islet in type 2 diabetes is characterized by an approximately 60% beta-cell deficit, increased beta-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (hIAPP) but not rodent IAPP (rIAPP) forms toxic oligomers and amyloid fibrils in an aqueous environment. We previously reported that overexpression of hIAPP in transgenic rats triggered endoplasmic reticulum (ER) stress-induced apoptosis in beta-cells.

Skin tolerance: in search of the Holy Grail.

In 1943, Gibson and Medawar opened the modern era of transplantation research with a paper on the problem of skin allograft rejection. Ten years later Billingham, Brent and Medawar demonstrated that it was possible to induce selective immune acceptance of skin grafts in mice, a state of tolerance. After over six decades, however, the precise mechanism of skin allograft rejection remains still ill-defined.

Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers.

Background: Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular Abeta and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils.

Assessing surgical skill using bench station models.

Background: The acquisition of surgical skill is one of the essentials of good surgical practice. The training of plastic surgeons is presently unstructured, with few objective measures of surgical skill. The trainee's time to acquire skills may be inadequate because of the shortened time for training with the Calman system.

Macrorheology and adaptive microrheology of endothelial cells subjected to fluid shear stress.

Vascular endothelial cells (ECs) respond to temporal and spatial characteristics of hemodynamic forces by alterations in their adhesiveness to leukocytes, secretion of vasodilators, and permeability to blood-borne constituents. These physiological and pathophysiological changes are tied to adaptation of cell mechanics and mechanotransduction, the process by which cells convert forces to intracellular biochemical signals. The exact time scales of these mechanical adaptations, however, remain unknown.

Finite element analysis of microelectrotension of cell membranes.

Electric fields can be focused by micropipette-based electrodes to induce stresses on cell membranes leading to tension and poration. To date, however, these membrane stress distributions have not been quantified. In this study, we determine membrane tension, stress, and strain distributions in the vicinity of a microelectrode using finite element analysis of a multiscale electro-mechanical model of pipette, media, membrane, actin cortex, and cytoplasm.

An artificial prosthesis to reconstruct donor defects following facial transplantation.

Post-harvest donor facial appearance is likely to have an impact on both the donor family and the transplant harvest team. We describe a method of fabricating a donor-specific artificial prosthesis, which can be constructed within the time frame of the facial graft harvest.

The use of color Doppler ultrasound in the assessment of vessels for facial transplantation.

The facial artery has been proposed as the main vascular pedicle in facial transplantation. An anatomic study of 200 consecutive facial and transverse facial vessels in 100 normal individuals was performed using color Doppler ultrasound. The diameter and course of each facial vessel were measured at 3 fixed landmarks, and the branching pattern was documented up to the level of the nasal ala.

Modulation of intracellular reactive oxygen species level in chondrocytes by IGF-1, FGF, and TGF-beta1.

Growth factors are important in the development, maintenance and repair of cartilage. The principal aim of this study was to test the capacity of three growth factors with established roles in cartilage, namely insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF) and transforming growth factor (TGF)-beta 1, to alter intracellular reactive oxygen species (ROS) levels. Explants of articular cartilage from young, mature, and aged rats were pretreated with IGF-1, FGF, or TGF-beta 1 and intracellular ROS levels were quantified using the free radical sensing probe dihydrorhodamine 123 (DHR 123), confocal microscopy, and densitometric image analysis.

High expression rates of human islet amyloid polypeptide induce endoplasmic reticulum stress mediated beta-cell apoptosis, a characteristic of humans with type 2 but not type 1 diabetes.

Objective: Endoplasmic reticulum (ER) stress-induced apoptosis may be a common cause of cell attrition in diseases characterized by misfolding and oligomerisation of amyloidogenic proteins. The islet in type 2 diabetes is characterized by islet amyloid derived from islet amyloid polypeptide (IAPP) and increased beta-cell apoptosis. We questioned the following: 1) whether IAPP-induced beta-cell apoptosis is mediated by ER stress and 2) whether beta-cells in type 2 diabetes are characterized by ER stress.

Hematopoietic stem cells derived from adult donors are not a source of pancreatic beta-cells in adult nondiabetic humans.

Objective: Type 1 and type 2 diabetes are characterized by an approximately 98 and approximately 65% loss of pancreatic beta-cells, respectively. Efforts to reverse either form of diabetes increasingly focus on the possibility of promoting beta-cell replacement and/or regeneration. Islet transplantation has been explored, but it does not provide long-term insulin independence.

Vascular delay revisited.

The technique of vascular delay has been used by plastic surgeons for nearly 500 years and has proven useful for reliably transferring tissue and allowing for a greater volume of tissue to be reliably harvested. Delay procedures are an essential plastic surgical tool for a variety of aesthetic and reconstructive procedures. Despite the widespread use of vascular delay procedures, the mechanism by which this phenomenon occurs remains unclear.

Silsesquioxane nanocomposites as tissue implants.

Background: Silicone implants are being used increasingly worldwide, especially in breast augmentation procedures. The most common morbidity observed is capsular contracture, which occurs in 15 percent of cases. To overcome this problem, the authors have developed a novel nanocomposite based on polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU) for use as tissue implants.