Optimising collagen scaffold architecture for enhanced periodontal ligament fibroblast migration.

Design of cell-free scaffolds for endogenous cell recruitment requires an intimate knowledge of precise relationships between structure and biological function. Here, we use morphological analysis by Micro-CT to identify the key structural features necessary for periodontal ligament fibroblast recruitment into collagen scaffolds. By the combined use of time-lapse imaging and end-point invasion analysis, we distinguish the influences of pore size, pore wall alignment, and pore transport pathways (percolation diameter) on the individual cell migration and bulk invasion characteristics of these fibroblasts.

BMP signaling regulates the fate of chondro-osteoprogenitor cells in facial mesenchyme in a stage-specific manner.

Background: Lineage tracing has shown that most of the facial skeleton is derived from cranial neural crest cells. However, the local signals that influence postmigratory, neural crest-derived mesenchyme also play a major role in patterning the skeleton. Here, we study the role of BMP signaling in regulating the fate of chondro-osteoprogenitor cells in the face.

Parameterizing the Transport Pathways for Cell Invasion in Complex Scaffold Architectures.

Interconnecting pathways through porous tissue engineering scaffolds play a vital role in determining nutrient supply, cell invasion, and tissue ingrowth. However, the global use of the term "interconnectivity" often fails to describe the transport characteristics of these pathways, giving no clear indication of their potential to support tissue synthesis. This article uses new experimental data to provide a critical analysis of reported methods for the description of scaffold transport pathways, ranging from qualitative image analysis to thorough structural parameterization using X-ray Micro-Computed Tomography.

Cell Invasion in Collagen Scaffold Architectures Characterized by Percolation Theory.

The relationship between biological scaffold interconnectivity and cell migration is an important but poorly understood factor in tissue regeneration. Here a scale-independent technique for characterization of collagen scaffold interconnectivity is presented, using a combination of X-ray microcomputed tomography and percolation theory. Confocal microscopy of connective tissue cells reveals this technique as highly relevant for determining the extent of cell invasion.

Small molecule stimulation enhances bone regeneration but not titanium implant osseointegration.

The osteogenic and osseointegrative potential of a small molecule was examined to assess its usefulness in regenerative procedures. Purmorphamine was used to stimulate bone growth and repair in an in vitro cell-based assay and an in vivo chick embryo CAM-assay with and without the presence of an implant. Purmorphamine adhered to precipitated hydroxyapatite coating, could activate the sonic hedgehog pathway and thereby stimulated osteodifferentiation.

Cell attachment and response to photocured, degradable bone adhesives containing tricalcium phosphate and purmorphamine.

The aim of this study was to quantify and provide evidence as to how addition of tricalcium phosphate (β-TCP) and the Hedgehog agonist purmorphamine to a degradable bone adhesive affects cell attachment/proliferation and Hedgehog pathway activation. Fourier transform infrared spectroscopy demonstrated that high levels (75 wt.%) of β-TCP addition reduced the photocure rate of the chosen poly(propylene glycol-co-lactide) dimethacrylate (PPLM) bone adhesive, but this problem was overcome by increased light exposure.

Reactive calcium-phosphate-containing poly(ester-co-ether) methacrylate bone adhesives: chemical, mechanical and biological considerations.

A poly(propylene glycol-co-lactide) dimethacrylate adhesive with monocalcium phosphate monohydrate (MCPM)/beta-tricalcium phosphate (beta-TCP) fillers in various levels has been investigated. Water sorption by the photo-polymerized materials catalyzed varying filler conversion to dicalcium phosphate (DCP). Polymer modulus was found to be enhanced upon raising total calcium phosphate content.

Mechanical regulation of secondary chondrogenesis.

The development of the skull is characterised by its dependence upon epigenetic influences. One of the most important of these is secondary chondrogenesis, which occurs following ossification within certain membrane bone periostea, as a result of biomechanical articulation. We have studied the genesis, character and function of the secondary chondrocytes of the quadratojugal of the chick between embryonic days 11 and 14.

The chicken talpid3 gene encodes a novel protein essential for Hedgehog signaling.

Talpid3 is a classical chicken mutant with abnormal limb patterning and malformations in other regions of the embryo known to depend on Hedgehog signaling. We combined the ease of manipulating chicken embryos with emerging knowledge of the chicken genome to reveal directly the basis of defective Hedgehog signal transduction in talpid3 embryos and to identify the talpid3 gene. We show in several regions of the embryo that the talpid3 phenotype is completely ligand independent and demonstrate for the first time that talpid3 is absolutely required for the function of both Gli repressor and activator in the intracellular Hedgehog pathway.

Muscling in on stem cells.

Skeletal muscle is one of the few adult tissues that possesses the capacity for regeneration (restoration of lost functional tissue) as opposed to repair. This capacity is due to the presence of 'muscle stem cells' known as satellite cells. Detailed investigation of these cells over the past 50 years has revealed that both these and other cells within the skeletal muscle complex are capable of regenerating both muscle and other cell types as well.

Craniofacial development in the talpid3 chicken mutant.

The talpid(3) chicken mutant has a pleiotropic phenotype including polydactyly and craniofacial abnormalities. Limb polydactyly in talpid(3) suggests a gain of Hedgehog (Hh) signaling, whereas, paradoxically, absence of midline facial structures suggests a loss of Hh function. Here we analyze the status of Shh signaling in the talpid(3) mutant head.

Secondary chondrocyte-derived Ihh stimulates proliferation of periosteal cells during chick development.

The development of the skull is characterised by its dependence upon epigenetic influences. One of the most important of these is secondary chondrogenesis, which occurs following ossification within certain membrane bone periostea, as a result of biomechanical articulation. We have studied the genesis, character and function of the secondary chondrocytes of the quadratojugal of the chick between embryonic days 11 and 14.

Wnt signalling regulates myogenic differentiation in the developing avian wing.

The limb musculature arises by delamination of premyogenic cells from the lateral dermomyotome. Initially the cells express Pax3 but, upon entering the limb bud, they switch on the expression of MyoD and Myf5 and undergo terminal differentiation into slow or fast fibres, which have distinct contractile properties that determine how a muscle will function. In the chick, the premyogenic cells express the Wnt antagonist Sfrp2, which is downregulated as the cells differentiate, suggesting that Wnts might regulate myogenic differentiation.