Penile prosthesis insertion for acute priapism.

Shunt surgery is not universally successful toward detumescence, may lead to erectile dysfunction, and can make eventual penile prosthesis insertion difficult. Penile prosthesis insertion during a priapistic episode alleviates ischemic pain, allows the patient to resume sexual function sooner, and prevents corporal scarring and shortening that makes subsequent prosthesis implantation difficult.

Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis.

Methacrylated hyaluronic acid (HA) hydrogels provide a backbone polymer with which mesenchymal stem cells (MSCs) can interact through several cell surface receptors that are expressed by MSCs, including CD44 and CD168. Previous studies showed that this 3D hydrogel environment supports the chondrogenesis of MSCs, and here we demonstrate through functional blockade that these specific cell-material interactions play a role in this process. Beyond matrix interactions, cadherin molecules, a family of transmembrane glycoproteins, play a critical role in tissue development during embryogenesis, and N-cadherin is a key factor in mediating cell-cell interactions during mesenchymal condensation and chondrogenesis.

Tissue engineering for articular cartilage repair--the state of the art.

Articular cartilage exhibits little capacity for intrinsic repair, and thus even minor injuries or lesions may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. While there have been numerous attempts to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, there remain significant challenges in the clinical application of cell-based therapies for cartilage repair. This paper reviews the current state of cartilage tissue engineering with respect to different cell sources and their potential genetic modification, biomaterial scaffolds and growth factors, as well as preclinical testing in various animal models.

Acellular biomaterials: an evolving alternative to cell-based therapies.

Acellular biomaterials can stimulate the local environment to repair tissues without the regulatory and scientific challenges of cell-based therapies. A greater understanding of the mechanisms of such endogenous tissue repair is furthering the design and application of these biomaterials. We discuss recent progress in acellular materials for tissue repair, using cartilage and cardiac tissues as examples of applications with substantial intrinsic hurdles, but where human translation is now occurring.

Biomaterial-mediated delivery of degradative enzymes to improve meniscus integration and repair.

Endogenous repair of fibrous connective tissues is limited, and there exist few successful strategies to improve healing after injury. As such, new methods that advance repair by promoting cell growth, extracellular matrix (ECM) production, and tissue integration would represent a marked clinical advance. Using the meniscus as a test platform, we sought to develop an enzyme-releasing scaffold that enhances integrative repair.

Biaxial mechanics and inter-lamellar shearing of stem-cell seeded electrospun angle-ply laminates for annulus fibrosus tissue engineering.

The annulus fibrosus (AF) of the intervertebral disk plays a critical role in vertebral load transmission that is heavily dependent on the microscale structure and composition of the tissue. With degeneration, both structure and composition are compromised, resulting in a loss of AF mechanical function. Numerous tissue engineering strategies have addressed the issue of AF degeneration, but few have focused on recapitulation of AF microstructure and function.

Tissue engineering and regenerative medicine: recent innovations and the transition to translation.

The field of tissue engineering and regenerative medicine (TERM) has exploded in the last decade. In this Year (or so) in Review, we highlight some of the high impact advances within the field over the past several years. Using the past as our guide and starting with an objective premise, we attempt so to identify recent "hot topics" and transformative publications within the field.

Organized nanofibrous scaffolds that mimic the macroscopic and microscopic architecture of the knee meniscus.

The menisci are crescent-shaped fibrocartilaginous tissues whose structural organization consists of dense collagen bundles that are locally aligned but show a continuous change in macroscopic directionality. This circumferential patterning is necessary for load transmission across the knee joint and is a key design parameter for tissue engineered constructs. To address this issue we developed a novel electrospinning method to produce scaffolds composed of circumferentially aligned (CircAl) nanofibers, quantified their structure and mechanics, and compared them with traditional linearly aligned (LinAl) scaffolds.

The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy.

Hyaluronic acid (HA) hydrogels formed via photocrosslinking provide stable 3D hydrogel environments that support the chondrogenesis of mesenchymal stem cells (MSCs). Crosslinking density has a significant impact on the physical properties of hydrogels, including their mechanical stiffness and macromolecular diffusivity. Variations in the HA hydrogel crosslinking density can be obtained by either changes in the HA macromer concentration (1, 3, or 5% w/v at 15 min exposure) or the extent of reaction through light exposure time (5% w/v at 5, 10, or 15 min).

Porosity and cell preseeding influence electrospun scaffold maturation and meniscus integration in vitro.

Electrospinning generates fibrous scaffolds ideal for engineering soft orthopedic tissues. By modifying the electrospinning process, scaffolds with different structural organization and content can be generated. For example, fibers can be aligned in a single direction, or the porosity of the scaffold can be modified through the use of multi-jet electrospinning and the removal of sacrificial fibers.

Sacrificial nanofibrous composites provide instruction without impediment and enable functional tissue formation.

The fibrous tissues prevalent throughout the body possess an ordered structure that underlies their refined and robust mechanical properties. Engineered replacements will require recapitulation of this exquisite architecture in three dimensions. Aligned nanofibrous scaffolds can dictate cell and matrix organization; however, their widespread application has been hindered by poor cell infiltration due to the tight packing of fibers during fabrication.

IL-1ra delivered from poly(lactic-co-glycolic acid) microspheres attenuates IL-1β-mediated degradation of nucleus pulposus in vitro.

Introduction: Inflammation plays a key role in the progression of intervertebral disc degeneration, a condition strongly implicated as a cause of lower back pain. The objective of this study was to investigate the therapeutic potential of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with interleukin-1 receptor antagonist (IL-1ra) for sustained attenuation of interleukin-1 beta (IL-1β) mediated degradative changes in the nucleus pulposus (NP), using an in vitro model.

Methods: IL-1ra was encapsulated in PLGA microspheres and release kinetics were determined over 35 days.

Sliding contact loading enhances the tensile properties of mesenchymal stem cell-seeded hydrogels.

The primary goal of cartilage tissue engineering is to recapitulate the functional properties and structural features of native articular cartilage. While there has been some success in generating near-native compressive properties, the tensile properties of cell-seeded constructs remain poor, and key features of cartilage, including inhomogeneity and anisotropy, are generally absent in these engineered constructs. Therefore, in an attempt to instill these hallmark properties of cartilage in engineered cell-seeded constructs, we designed and characterized a novel sliding contact bioreactor to recapitulate the mechanical stimuli arising from physiologic joint loading (two contacting cartilage layers).

Growth factor supplementation improves native and engineered meniscus repair in vitro.

Few therapeutic options exist for meniscus repair after injury. Local delivery of growth factors may stimulate repair and create a favorable environment for engineered replacement materials. In this study we assessed the effect of basic fibroblast growth factor (bFGF) (a pro-mitotic agent) and transforming growth factor β3 (TGF-β3) (a pro-matrix formation agent) on meniscus repair and the integration/maturation of electrospun poly(ε-caprolactone) (PCL) scaffolds for meniscus tissue engineering.

Mesenchymal stem cells produce functional cartilage matrix in three-dimensional culture in regions of optimal nutrient supply.

Mesenchymal stem cells (MSCs) are a promising cell source for the treatment of musculoskeletal disease. However, MSC chondrogenesis in 3D culture generates constructs whose macroscopic (bulk) mechanical properties are inferior to constructs formed with chondrocytes. To investigate where and why these deficits in functionality arise, we assessed the local (microscopic) properties of cell-laden hydrogel constructs.

Transient exposure to TGF-β3 improves the functional chondrogenesis of MSC-laden hyaluronic acid hydrogels.

Tissue engineering with adult stem cells is a promising approach for the restoration of focal defects in articular cartilage. For this, progenitor cells would ideally be delivered to (and maintained within) the defect site via a biocompatible material and in combination with soluble factors to promote initial cell differentiation and subsequent tissue maturation in vivo. While growth factor delivery methods are continually being optimized, most offer only a short (days to weeks) delivery profile at high doses.

High mesenchymal stem cell seeding densities in hyaluronic acid hydrogels produce engineered cartilage with native tissue properties.

Engineered cartilage based on adult mesenchymal stem cells (MSCs) is an alluring goal for the repair of articular defects. However, efforts to date have failed to generate constructs with sufficient mechanical properties to function in the demanding environment of the joint. Our findings with a novel photocrosslinked hyaluronic acid (HA) hydrogel suggest that stiff gels (high HA concentration, 5% w/v) foster chondrogenic differentiation and matrix production, but limit overall functional maturation due to the inability of the formed matrix to diffuse away from the point of production and form a contiguous network.

Improved cartilage repair via in vitro pre-maturation of MSC-seeded hyaluronic acid hydrogels.

Functional repair of focal cartilage defects requires filling the space with neotissue that has compressive properties comparable to native tissue and integration with adjacent host cartilage. While poor integration is a common complication with current clinical treatments, reports of tissue engineering advances in the development of functional compressive properties rarely include analyses of their potential for integration. Our objective was thus to assess both the maturation and integration of mesenchymal stem cell (MSC)-laden hyaluronic acid (HA) hydrogels in an in vitro cartilage defect model.

Multi-scale structural and tensile mechanical response of annulus fibrosus to osmotic loading.

This study investigates differential multi-scale structure and function relationships of the outer and inner annulus fibrosus (AF) to osmotic swelling in different buffer solutions by quantifying tensile mechanics, glycoasamino-glycan(GAG) content, water content and tissue swelling, and collagen fibril ultrastructure. In the outer AF, the tensile modulus decreased by over 70% with 0.15 M PBS treatment but was unchanged with 2 M PBS treatment.

Fabrication and evaluation of biomimetic-synthetic nanofibrous composites for soft tissue regeneration.

Electrospun scaffolds hold promise for the regeneration of dense connective tissues, given their nanoscale topographies, provision of directional cues for infiltrating cells and versatile composition. Synthetic slow-degrading scaffolds provide long-term mechanical support and nanoscale instructional cues; however, these scaffolds suffer from a poor infiltration rate. Alternatively, nanofibrous constructs formed from natural biomimetic materials (such as collagen) rapidly infiltrate but provide little mechanical support.

Fiber-aligned polymer scaffolds for rotator cuff repair in a rat model.

Background: Repair techniques of rotator cuff tendon tears have improved in recent years; nonetheless, the failure rate remains high. Despite the availability of various graft materials for repair augmentation, there has yet to be a biomechanical study using fiber-aligned scaffolds in vivo. The objective of this study was to evaluate the efficacy of fiber-aligned nanofibrous polymer scaffolds as a potential treatment-delivery vehicle in a rat rotator cuff injury model.

Nucleus pulposus cells synthesize a functional extracellular matrix and respond to inflammatory cytokine challenge following long-term agarose culture.

Intervertebral disc degeneration is characterized by a cascade of cellular, biochemical and structural changes that may lead to functional impairment and low back pain. Interleukin-1 beta (IL-1β) is strongly implicated in the etiology of disc degeneration, however there is currently no direct evidence linking IL-1β upregulation to downstream biomechanical changes. The objective of this study was to evaluate long-term agarose culture of nucleus pulposus (NP) cells as a potential in vitro model system to investigate this.

Fiber angle and aspect ratio influence the shear mechanics of oriented electrospun nanofibrous scaffolds.

Fibrocartilages, including the knee meniscus and the annulus fibrosus (AF) of the intervertebral disc, play critical mechanical roles in load transmission across joints and their function is dependent upon well-defined structural hierarchies, organization, and composition. All, however, are compromised in the pathologic transformations associated with tissue degeneration. Tissue engineering strategies that address these key features, for example, aligned nanofibrous scaffolds seeded with mesenchymal stem cells (MSCs), represent a promising approach for the regeneration of these fibrous structures.