Improving cartilage phenotype from differentiated pericytes in tunable peptide hydrogels

Differentiation of stem cells to chondrocytes in vitro usually results in a heterogeneous phenotype. This is evident in the often detected over expression of type X collagen which, in hyaline cartilage structure is not characteristic of the mid-zone but of the deep-zone ossifying tissue. Methods to better match cartilage developed in vitro to characteristic in vivo features are therefore highly desirable in regenerative medicine. This study compares phenotype characteristics between pericytes, obtained from human adipose tissue, differentiated using diphenylalanine/serine (F2/S) peptide hydrogels with the more widely used chemical induced method for chondrogenesis. Significantly higher levels of type II collagen were noted when pericytes undergo chondrogenesis in the hydrogel in the absence of induction media. There is also a balanced expression of collagen relative to aggrecan production, a feature which was biased toward collagen production when cells were cultured with induction media. Lastly, metabolic profiles of each system show considerable overlap between both differentiation methods but subtle differences which potentially give rise to their resultant phenotype can be ascertained. The study highlights how material and chemical alterations in the cellular microenvironment have wide ranging effects on resultant tissue type

Bioresponsive hydrogels

We highlight recent developments in hydrogel materials with biological responsiveness built in. These ‘smart’ biomaterials change properties in response to selective biological recognition events. When exposed to a biological target (nutrient, growth factor, receptor, antibody, enzyme, or whole cell), molecular recognition events trigger changes in molecular interactions that translate into macroscopic responses, such as swelling/collapse or solution-to-gel transitions. The hydrogel transitions may be used directly as optical readouts for biosensing, linked to the release of actives for drug delivery, or instigate biochemical signaling events that control or direct cellular behavior. Accordingly, bioresponsive hydrogels have gained significant interest for application in diagnostics, drug delivery, and tissue regeneration/wound healing

Using Rheo-Small-Angle Neutron Scattering to Understand How Functionalised Dipeptides Form Gels

We explore the use of rheo-small-angle neutron scattering as a method to collect structural information from neutron scattering simultaneously with rheology to understand how low-molecular-weight hydrogels form and behave under shear. We examine three different gelling hydrogel systems to assess what structures are formed and how these influence the rheology. Furthermore, we probe what is happening to the network during syneresis and why the gels do not recover after an applied strain. All this information is vital when considering gels for applications such as 3D-printing and injection

Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that are of considerable clinical potential in transplantation and anti-inflammatory therapies due to their capacity for tissue repair and immunomodulation. However, MSCs rapidly differentiate once in culture, making their large-scale expansion for use in immunomodulatory therapies challenging. Although the differentiation mechanisms of MSCs have been extensively investigated using materials, little is known about how materials can influence paracrine activities of MSCs. Here, we show that nanotopography can control the immunomodulatory capacity of MSCs through decreased intracellular tension and increasing oxidative glycolysis. We use nanotopography to identify bioactive metabolites that modulate intracellular tension, growth and immunomodulatory phenotype of MSCs in standard culture and during larger scale cell manufacture. Our findings demonstrate an effective route to support large-scale expansion of functional MSCs for therapeutic purposes

Collaborating for Innovation: the socialised management of knowledge

Although the importance of diverse knowledge is widely recognised for open innovation, there may be a gap in our understanding of the social processes that shape how collaborators engage in knowledge exchange. This social gap may be significant because of the powerful, but largely unexplained, role attributed to trust as a social artefact. Moreover, we see trust as a process and that different types of trust are involved in the collaborative process. Thus, this paper uses a qualitative methodology to capture the experiences of innovation collaborators. As explanation of the dynamic interplays of knowledge and trust, we offer a description of phases in the process. Our analysis finds that the relationship moves from transactional to social. The early phases are characterised by technical knowledge, but the later and mature phases are identified with knowledge of the person and by personal trust. The success of innovation is a result of relationships with augmented trust. We found that a fabric of trust is woven from the weft of professional knowledge and the warp of personal knowledge to support innovation. We propose that this developing of relationships might be conceived as becoming more open in the sense of sharing with one another. If so, we seem to have described and offered a social dimension of open innovation

Three-dimensional cell culture of chondrocytes on modified di-phenylaianine scaffolds

The design of self-assembled peptide-based structures for three-dimensional cell culture and tissue repair has been a key objective in biomaterials science for decades. in search of the simplest possible peptide system that can self-assemble, we discovered that combinations of di-peptides that are modified with aromatic stacking ligands could form nanometre-sized fibres when exposed to physiological conditions. For example, we demonstrated that a number of Fmoc (fluoren-9-ylmethyloxycarbonyl) modified di- and tri-peptides form highly ordered hydrogels via hydrogen-bonding and pi-pi interactions from the fluorenyl rings. These highly hydrated gels allowed for cell proliferation of chondrocytes in three dimensions [Jayawarna, Ali, Jowitt, Miller, Sal Gough and Ulijn (2006) Adv. Mater. 18, 611-614]. We demonstrated that fibrous architecture and physical properties of the resulting materials were dictated by the nature of the amino acid building blocks. Here, we report the self-assembly process of three di-phenylalanine analogues, Fmoc-Phe-Phe-OH, Nap (naphthalene)-Phe-Phe-OH and Cbz (benzyloxycarbonyl)-Phe-Phe-OH, to compare and contrast the self-assembly properties and cell culture conditions attributable to their protecting group difference. Fibre morphology analysis of the three structures using cryo-SEM (scanning electron microscopy) and TEM (transmission electron microscopy) suggested fibrous structures with dramatically varying fibril dimensions, depending on the aromatic ligand used. CD and FTIR (Fourier-transform IR) data confirmed beta-sheet arrangements in all three samples in the gel state. The ability of these three new hydrogels to support cell proliferation of chondrocytes was confirmed for all three materials

Enzyme-triggered self-assembly of peptide hydrogels via reversed hydrolysis

This paper looks at enzyme-triggered self-assembly of peptide hydrogels via reversed hydrolysi

Post lumbar puncture headache: diagnosis and management

Lumbar puncture is a frequently performed procedure in medical emergencies and anaesthesia. Headache after lumbar puncture is a common occurrence (32%) and carries a considerable morbidity, with symptoms lasting for several days, at times severe enough to immobilise the patient. If untreated, it can result in serious complications such as subdural haematoma and seizures, which could be fatal. Certain factors contribute to the development of headache after lumbar puncture. If these factors are taken into consideration, the incidence of headache could be markedly reduced. It is therefore important that the doctors are aware of the methods available for reducing the incidence of headaches after lumbar puncture. On the other hand, there are several misconceptions that are thought to decrease the incidence of headaches with no scientific basis. This article reviews the scientific literature and highlights the practical issues involved in the diagnosis and management of headaches after lumbar puncture, including the epidural blood patch treatment