Efficient differentiation of human embryonic stem cells to retinal pigment epithelium under defined conditions.

Unlabelled: Age-related macular degeneration (AMD) is a highly prevalent form of blindness caused by loss death of cells of the retinal pigment epithelium (RPE). Transplantation of pluripotent stem cell (PSC)-derived RPE cells is considered a promising therapy to regenerate cell function and vision.

Objective: The objective of this study is to develop a rapid directed differentiation method for production of RPE cells from PSC which is rapid, efficient, and fully defined and produces cells suitable for clinical use.

Hydrogels with Cell Adhesion Peptide-Decorated Channel Walls for Cell Guidance.

A method is reported for making hollow channels within hydrogels decorated with cell-adhesion peptides exclusively at the channel surface. Sacrificial fibers of different diameters are used to introduce channels within poly(ethylene glycol) hydrogels crosslinked with maleimide-thiol chemistry, which are backfilled with a cysteine-containing peptide solution which is conjugated to the lumen with good spatial efficiency. This allows for peptide patterning in only the areas of the hydrogel where they are needed when used as cell-guides, reducing the amount of required peptide 20-fold when compared to bulk functionalization.

Going beyond RGD: screening of a cell-adhesion peptide library in 3D cell culture.

In tissue engineering, cell-adhesion peptides (CAPs) such as the ubiquitous arginine-glycine-aspartic acid (RGD) sequence have allowed the functionalization of synthetic materials to mimic macromolecules of the extracellular matrix (ECM). However, the variety of ECM macromolecules makes it challenging to reproduce all of the native tissue functions with only a limited variety of CAPs. Screening of libraries of CAPs, analogous to high-throughput drug discovery assays, can help to identify new sequences directing cell organization.

Design, development and characterization of synthetic Bruch's membranes.

Unlabelled: Age-related macular degeneration (AMD) is a leading cause of blindness, and dry AMD has no effective treatment. Retinal constructs comprising retinal pigment epithelium (RPE) cells supported by electrospun scaffolds have been investigated to treat dry AMD. However, electrospun scaffolds studied to-date do not mimic the structural microenvironment of human Bruch's membrane (BM), essential for native-like RPE monolayers.

Large-scale expansion of human skin-derived precursor cells (hSKPs) in stirred suspension bioreactors.

Human skin-derived precursor cells (hSKPs) are multipotent adult stem cells found in the dermis of human skin. Incorporation of hSKPs into split-thickness skin grafts (STSGs), the current gold standard to treat severe burns or tissue resections, has been proposed as a treatment option to enhance skin wound healing and tissue function. For this approach to be clinically viable substantial quantities of hSKPs are required, which is the rate-limiting step, as only a few thousand hSKPs can be isolated from an autologous skin biopsy without causing donor site morbidity.

Biomimetic poly(lactide) based fibrous scaffolds for ligament tissue engineering.

The aim of this study was to fabricate a fibrous scaffold that closely resembled the micro-structural architecture and mechanical properties of collagen fibres found in the anterior cruciate ligament (ACL). To achieve this aim, fibrous scaffolds were made by electrospinning L-lactide based polymers. L-Lactide was chosen primarily due to its demonstrated biocompatibility, biodegradability and high modulus.

A crimp-like microarchitecture improves tissue production in fibrous ligament scaffolds in response to mechanical stimuli.

The aim of this study was to determine the influence of a crimp-like microarchitecture within electrospun polymer scaffolds on fibroblast extracellular matrix (ECM) production when cultured under dynamic conditions. Electrospun poly(L-lactide-co-D,L-lactide) scaffolds possessing a wave pattern similar to collagen crimp (amplitude: 5 μm and wavelength: 46 μm) were seeded with bovine fibroblasts and mechanically stimulated under dynamic uniaxial tension. The effect of strain amplitude (5%, 10% and 20%) was investigated in a short-term stimulation study.

The importance of bicarbonate and nonbicarbonate buffer systems in batch and continuous flow bioreactors for articular cartilage tissue engineering.

In cartilage tissue engineering an optimized culture system, maintaining an appropriate extracellular environment (e.g., pH of media), can increase cell proliferation and extracellular matrix (ECM) accumulation.

Can microcarrier-expanded chondrocytes synthesize cartilaginous tissue in vitro?

Tissue engineering is a promising approach for articular cartilage repair; however, it is challenging to produce adequate amounts of tissue in vitro from the limited number of cells that can be extracted from an individual. Relatively few cell expansion methods exist without the problems of de-differentiation and/or loss of potency. Recently, however, several studies have noted the benefits of three-dimensional (3D) over monolayer expansion, but the ability of 3D expanded chondrocytes to synthesize cartilaginous tissue constructs has not been demonstrated.

Self-crimping, biodegradable, electrospun polymer microfibers.

Semicrystalline poly(l-lactide-co-ε-caprolactone) (P(LLA-CL)) was used to produce electrospun fibers with diameters on the subcellular scale. P(LLA-CL) was chosen because it is biocompatible and its chemical and physical properties are easily tunable. The use of a rotating wire mandrel as a collection device in the electrospinning process, along with high collection speeds, was used to align electrospun fibers.

Design and characterization of a biodegradable composite scaffold for ligament tissue engineering.

Herein we report on the development and characterization of a biodegradable composite scaffold for ligament tissue engineering based on the fundamental morphological features of the native ligament. An aligned fibrous component was used to mimic the fibrous collagen network and a hydrogel component to mimic the proteoglycan-water matrix of the ligament. The composite scaffold was constructed from cell-adherent, base-etched, electrospun poly(epsilon-caprolactone-co-D,L-lactide) (PCLDLLA) fibers embedded in a noncell-adherent photocrosslinked N-methacrylated glycol chitosan (MGC) hydrogel seeded with primary ligament fibroblasts.