Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast.

Transplantation of functional islets encapsulated in stable biomaterials has the potential to cure Type I diabetes. However, the success of these materials requires the ability to quantitatively evaluate their stability. Imaging techniques that enable monitoring of biomaterial performance are critical to further development in the field.

X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants.

Three dimensional imaging techniques are needed for the evaluation and assessment of biomaterials used for tissue engineering and drug delivery applications. Hydrogels are a particularly popular class of materials for medical applications but are difficult to image in tissue using most available imaging modalities. Imaging techniques based on X-ray Phase Contrast (XPC) have shown promise for tissue engineering applications due to their ability to provide image contrast based on multiple X-ray properties.

Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation.

Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro, but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system.

Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in Sphere-Templated Hydrogels.

Rapid and controlled vascularization within biomaterials is essential for many applications in regenerative medicine. The extent of vascularization is influenced by a number of factors, including scaffold architecture. While properties such as pore size and total porosity have been studied extensively, the importance of controlling the interconnectivity of pores has received less attention.

X-ray phase contrast imaging of calcified tissue and biomaterial structure in bioreactor engineered tissues.

Tissues engineered in bioreactor systems have been used clinically to replace damaged tissues and organs. In addition, these systems are under continued development for many tissue engineering applications. The ability to quantitatively assess material structure and tissue formation is critical for evaluating bioreactor efficacy and for preimplantation assessment of tissue quality.

Label-free nondestructive imaging of vascular network structure in 3D culture.

Three-dimensional (3D) cell culture assays are important tools in the study of vessel assembly. Current techniques for quantitative analysis of vascular network structure have provided important insight into 3D vessel assembly. However, these methods typically require immunohistochemical staining, which requires sample destruction, or fluorescent cell labeling, which may alter cell behavior.

Imaging challenges in biomaterials and tissue engineering.

Biomaterials are employed in the fields of tissue engineering and regenerative medicine (TERM) in order to enhance the regeneration or replacement of tissue function and/or structure. The unique environments resulting from the presence of biomaterials, cells, and tissues result in distinct challenges in regards to monitoring and assessing the results of these interventions. Imaging technologies for three-dimensional (3D) analysis have been identified as a strategic priority in TERM research.

Evaluation of physical and mechanical properties of porous poly (ethylene glycol)-co-(L-lactic acid) hydrogels during degradation.

Porous hydrogels of poly(ethylene glycol) (PEG) have been shown to facilitate vascularized tissue formation. However, PEG hydrogels exhibit limited degradation under physiological conditions which hinders their ultimate applicability for tissue engineering therapies. Introduction of poly(L-lactic acid) (PLLA) chains into the PEG backbone results in copolymers that exhibit degradation via hydrolysis that can be controlled, in part, by the copolymer conditions.

MMP-sensitive PEG diacrylate hydrogels with spatial variations in matrix properties stimulate directional vascular sprout formation.

The spatial presentation of immobilized extracellular matrix (ECM) cues and matrix mechanical properties play an important role in directed and guided cell behavior and neovascularization. The goal of this work was to explore whether gradients of elastic modulus, immobilized matrix metalloproteinase (MMP)-sensitivity, and YRGDS cell adhesion ligands are capable of directing 3D vascular sprout formation in tissue engineered scaffolds. PEGDA hydrogels were engineered with mechanical and biofunctional gradients using perfusion-based frontal photopolymerization (PBFP).

Influence of crosslinking on the stiffness and degradation of dermis-derived hydrogels.

Natural hydrogels have been investigated for three-dimensional tissue reconstruction and regeneration given their ability to emulate the structural complexity of multi-component extracellular matrices (ECM). Hydrogels rich in ECM can be extracted and assembled from soft tissues, retain a composition specific to the tissue source, and stimulate vascularized tissue formation. However, poor mechanical properties and rapid degradation hinder their performance in regenerative applications.

Effective tuning of ligand incorporation and mechanical properties in visible light photopolymerized poly(ethylene glycol) diacrylate hydrogels dictates cell adhesion and proliferation.

Cell behavior is guided by the complex interplay of matrix mechanical properties as well as soluble and immobilized biochemical signals. The development of synthetic scaffolds that incorporate key functionalities of the native extracellular matrix (ECM) for support of cell proliferation and tissue regeneration requires that stiffness and immobilized concentrations of ECM signals within these biomaterials be tuned and optimized prior to in vitro and in vivo studies. A detailed experimental sensitivity analysis was conducted to identify the key polymerization conditions that result in significant changes in both elastic modulus and immobilized YRGDS within visible light photopolymerized poly(ethylene glycol) diacrylate hydrogels.

Analyzer-based phase-contrast x-ray imaging of carotid plaque microstructure.

Background: Plaque vulnerability depends, in part, on composition. Imaging techniques are needed that can aid the prediction of plaque stability. High-contrast images of soft-tissue structure have been obtained with x-ray phase-contrast (PC) imaging.

Fibrin-loaded porous poly(ethylene glycol) hydrogels as scaffold materials for vascularized tissue formation.

Vascular network formation within biomaterial scaffolds is essential for the generation of properly functioning engineered tissues. In this study, a method is described for generating composite hydrogels in which porous poly(ethylene glycol) (PEG) hydrogels serve as scaffolds for mechanical and structural support, and fibrin is loaded within the pores to induce vascularized tissue formation. Porous PEG hydrogels were generated by a salt leaching technique with 100-150-μm pore size and thrombin (Tb) preloaded within the scaffold.

Generation of alginate microspheres for biomedical applications.

Alginate-based materials have received considerable attention for biomedical applications because of their hydrophilic nature, biocompatibility, and physical architecture. Applications include cell encapsulation, drug delivery, stem cell culture, and tissue engineering scaffolds. In fact, clinical trials are currently being performed in which islets are encapsulated in PLO coated alginate microbeads as a treatment of type I diabetes.

Imaging of poly(α-hydroxy-ester) scaffolds with X-ray phase-contrast microcomputed tomography.

Porous scaffolds based on poly(α-hydroxy-esters) are under investigation in many tissue engineering applications. A biological response to these materials is driven, in part, by their three-dimensional (3D) structure. The ability to evaluate quantitatively the material structure in tissue-engineering applications is important for the continued development of these polymer-based approaches.

Investigation of lysine acrylate containing poly(N-isopropylacrylamide) hydrogels as wound dressings in normal and infected wounds.

The design of materials for cutaneous wound dressings has advanced from passive wound covers to bioactive materials that promote skin regeneration and prevent infection. Crosslinked poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogels have been investigated for a number of biomedical applications. While these materials can be used for drug delivery, limited cell interactions restrict their biological activity.

The role of pore size on vascularization and tissue remodeling in PEG hydrogels.

Vascularization is influenced by the physical architecture of a biomaterial. The relationship between pore size and vascularization has been examined for hydrophobic polymer foams, but there has been little research on tissue response in porous hydrogels. The goal of this study was to examine the role of pore size on vessel invasion in porous poly(ethylene glycol) (PEG) hydrogels.

Collagen glycation alters neovascularization in vitro and in vivo.

Microvascular network formation is required for the success of many therapies in regenerative medicine. The process of vessel assembly is fundamentally altered, however, in many people within the potential patient population, including the elderly and people with diabetes. Significant research has been performed to determine how cellular dysfunction contributes to this inadequate neovascularization, but alterations in the extracellular matrix (ECM) may also influence this process.

Generation of porous poly(ethylene glycol) hydrogels by salt leaching.

Poly(ethylene glycol) (PEG) hydrogels have been investigated for a number of applications in tissue engineering. The hydrogels can be designed to mimic tissues that have desired chemical and mechanical properties, but their physical structure can hinder cell migration, tissue invasion, and molecular transport. Synthesis of porous PEG hydrogels could improve transport, enhance cell behavior, and increase the surface area available for cell adhesion.

Characterization of type I collagen gels modified by glycation.

Chronic exposure to reducing sugars due to diabetes, aging, and diet can permanently modify extracellular matrix (ECM) proteins. This non-enzymatic glycosylation, or glycation, can lead to the formation of advanced glycation end products (AGE) and crosslinking of the ECM. This study investigates the effects of glycation on the properties of type I collagen gels.