Evaluation of a transtympanic delivery system in Mus musculus for extended release steroids.

Objective: The current investigation evaluated a novel extended release delivery system for treating inner ear diseases. The platform technology consists of a film forming agent (FFA) and microsphere component to localize and extend drug delivery within the ear.

Study Design: Studies evaluated dissolution kinetics of microspheres with multiple encapsulates, testing of a variety of FFAs, and ability to localize to the round window membrane in mice in vivo.

Palatability of a novel oral formulation of prednisone in healthy young adults.

Objectives: Prednisone is a widely used anti-inflammatory for a variety of conditions. While oral liquid formulations of prednisone enable weight-based dosing, children frequently find them to be objectionable due to bitter taste. This limitation of prednisone can adversely impact patient acceptance and may result in non-compliance.

Effect of different sintering methods on bioactivity and release of proteins from PLGA microspheres.

Macromolecule release from poly(d,l-lactide-co-glycolide) (PLGA) microspheres has been well-characterized, and is a popular approach for delivering bioactive signals from tissue-engineered scaffolds. However, the effect of some processing solvents, sterilization, and mineral incorporation (when used in concert) on long-term release and bioactivity has seldom been addressed. Understanding these effects is of significant importance for microsphere-based scaffolds, given that these scaffolds are becoming increasingly more popular, yet growth factor activity following sintering and/or sterilization is heretofore unknown.

Using chondroitin sulfate to improve the viability and biosynthesis of chondrocytes encapsulated in interpenetrating network (IPN) hydrogels of agarose and poly(ethylene glycol) diacrylate.

We recently introduced agarose-poly(ethylene glycol) diacrylate (PEGDA) interpenetrating network (IPN) hydrogels to cartilage tissue engineering that were able to encapsulate viable cells and provide a significant improvement in mechanical performance relative to its two constituent hydrogels. The goal of the current study was to develop a novel synthesis protocol to incorporate methacrylated chondroitin sulfate (MCS) into the IPN design hypothesized to improve cell viability and biosynthesis. The IPN was formed by encapsulating porcine chondrocytes in agarose, soaking the construct in a solution of 1:10 MCS:PEGDA, which was then photopolymerized to form a copolymer network as the second network.

Osteochondral interface regeneration of the rabbit knee with macroscopic gradients of bioactive signals.

To date, most interfacial tissue engineering approaches have used stratified designs, in which there are two or more discrete layers comprising the interface. Continuously graded interfacial designs, where there is no discrete transition from one tissue type to another, are gaining attention as an alternative to stratified designs. Given that osteochondral regeneration holds the potential to enhance cartilage regeneration by leveraging the healing capacity of the underlying bone, we endeavored to introduce a continuously-graded approach to osteochondral regeneration.

Osteogenic differentiation of human bone marrow stromal cells in hydroxyapatite-loaded microsphere-based scaffolds.

Calcium-based minerals have consistently been shown to stimulate osteoblastic behavior in vitro and in vivo. Thus, use of such minerals in biomaterial applications has become an effective method to enhance bone tissue engineered constructs. In the present study, for the first time, human bone marrow stromal cells (hBMSC) were osteogenically differentiated on scaffolds consisting only of hydroxyapatite (HAp)-loaded poly(D,L-lactic acid-co-glycolic acid) (PLGA) microspheres of high monodispersity.

Continuous gradients of material composition and growth factors for effective regeneration of the osteochondral interface.

Most contemporary biomaterial designs for osteochondral regeneration utilize monolithic, biphasic, or even multiphasic constructs. We have introduced a microsphere-based approach to create a continuous gradient in both material composition and encapsulated growth factors. The gradients were fabricated by filling a cylindrical mold with opposing gradients of two different types of poly(D,L-lactic-co-glycolic acid) microspheres.

Osteochondral interface regeneration of rabbit mandibular condyle with bioactive signal gradients.

Purpose: Tissue engineering solutions focused on the temporomandibular joint (TMJ) have expanded in number and variety during the past decade to address the treatment of TMJ disorders. The existing data on approaches for healing small defects in the TMJ condylar cartilage and subchondral bone, however, are sparse. The purpose of the present study was thus to evaluate the performance of a novel gradient-based scaffolding approach to regenerate osteochondral defects in the rabbit mandibular condyle.

Hierarchically designed agarose and poly(ethylene glycol) interpenetrating network hydrogels for cartilage tissue engineering.

A new method for encapsulating cells in interpenetrating network (IPN) hydrogels of superior mechanical integrity was developed. In this study, two biocompatible materials-agarose and poly(ethylene glycol) (PEG) diacrylate-were combined to create a new IPN hydrogel with greatly enhanced mechanical performance. Unconfined compression of hydrogel samples revealed that the IPN displayed a fourfold increase in shear modulus relative to a pure PEG-diacrylate network (39.

Emerging techniques in stratified designs and continuous gradients for tissue engineering of interfaces.

Interfacial tissue engineering is an emerging branch of regenerative medicine, where engineers are faced with developing methods for the repair of one or many functional tissue systems simultaneously. Early and recent solutions for complex tissue formation have utilized stratified designs, where scaffold formulations are segregated into two or more layers, with discrete changes in physical or chemical properties, mimicking a corresponding number of interfacing tissue types. This method has brought forth promising results, along with a myriad of regenerative techniques.

Osteochondral interface tissue engineering using macroscopic gradients of bioactive signals.

Continuous gradients exist at osteochondral interfaces, which may be engineered by applying spatially patterned gradients of biological cues. In the present study, a protein-loaded microsphere-based scaffold fabrication strategy was applied to achieve spatially and temporally controlled delivery of bioactive signals in three-dimensional (3D) tissue engineering scaffolds. Bone morphogenetic protein-2 and transforming growth factor-beta(1)-loaded poly(D,L-lactic-co-glycolic acid) microspheres were utilized with a gradient scaffold fabrication technology to produce microsphere-based scaffolds containing opposing gradients of these signals.

Three-dimensional macroscopic scaffolds with a gradient in stiffness for functional regeneration of interfacial tissues.

A novel approach has been demonstrated to construct biocompatible, macroporous 3-D tissue engineering scaffolds containing a continuous macroscopic gradient in composition that yields a stiffness gradient along the axis of the scaffold. Polymeric microspheres, made of poly(D,L-lactic-co-glycolic acid) (PLGA), and composite microspheres encapsulating a higher stiffness nano-phase material (PLGA encapsulating CaCO(3) or TiO(2) nanoparticles) were used for the construction of microsphere-based scaffolds. Using controlled infusion of polymeric and composite microspheres, gradient scaffolds displaying an anisotropic macroscopic distribution of CaCO(3)/TiO(2) were fabricated via an ethanol sintering technique.

Osteogenic differentiation of human umbilical cord mesenchymal stromal cells in polyglycolic acid scaffolds.

Although human umbilical cord mesenchymal stromal cells (hUCMSCs) have been shown to differentiate along an osteogenic lineage in monolayer culture, the potential of these cells has seldom before been investigated in three-dimensional scaffolds for bone tissue engineering applications. In this 6-week study, we observed osteogenic differentiation of hUCMSCs on polyglycolic acid (PGA) nonwoven mesh scaffolds, and compared seeding densities for potential use in bone tissue engineering. Cells were seeded into PGA meshes with densities of 5, 25, or 50 x 10(6) cells/mL scaffold and then cultured in osteogenic medium.