Tissue engineered autologous cartilage-bone grafts for temporomandibular joint regeneration.

Joint disorders can be detrimental to quality of life. There is an unmet need for precise functional reconstruction of native-like cartilage and bone tissues in the craniofacial space and particularly for the temporomandibular joint (TMJ). Current surgical methods suffer from lack of precision and comorbidities and frequently involve multiple operations.

Ectopic implantation of juvenile osteochondral tissues recapitulates endochondral ossification.

Subcutaneous implantation in a mouse can be used to investigate tissue maturation in vivo. Here we demonstrate that this simple model can recapitulate endochondral ossification associated with native skeletal development. By histological and micro-computed tomography analysis we investigated morphological changes of immature bovine osteochondral tissues over the course of subcutaneous implantation in immunocompromised mice for up to 10 weeks.

Stem cell delivery in tissue-specific hydrogel enabled meniscal repair in an orthotopic rat model.

Interest in non-invasive injectable therapies has rapidly risen due to their excellent safety profile and ease of use in clinical settings. Injectable hydrogels can be derived from the extracellular matrix (ECM) of specific tissues to provide a biomimetic environment for cell delivery and enable seamless regeneration of tissue defects. We investigated the in situ delivery of human mesenchymal stem cells (hMSCs) in decellularized meniscus ECM hydrogel to a meniscal defect in a nude rat model.

Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage.

Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction.

Extracellular matrix components and culture regimen selectively regulate cartilage formation by self-assembling human mesenchymal stem cells in vitro and in vivo.

Background: Cartilage formation from self-assembling mesenchymal stem cells (MSCs) in vitro recapitulate important cellular events during mesenchymal condensation that precedes native cartilage development. The goal of this study was to investigate the effects of cartilaginous extracellular matrix (ECM) components and culture regimen on cartilage formation by self-assembling human MSCs in vitro and in vivo.

Methods: Human bone marrow-derived MSCs (hMSCs) were seeded and compacted in 6.

Biomimetic Approaches for Bone Tissue Engineering.

Although autologous bone grafts are considered a gold standard for the treatment of bone defects, they are limited by donor site morbidities and geometric requirements. We propose that tissue engineering technology can overcome such limitations by recreating fully viable and biological bone grafts. Specifically, we will discuss the use of bone scaffolds and autologous cells with bioreactor culture systems as a tissue engineering paradigm to grow bone in vitro.

Mesenchymal Stem Cells for Osteochondral Tissue Engineering.

Mesenchymal stem cells (MSC) are of major interest in regenerative medicine, as they are easily harvested from a variety of sources (including bone marrow and fat aspirates) and they are able to form a range of mesenchymal tissues, in vitro and in vivo. We focus here on the use of MSCs for engineering of cartilage, bone, and complex osteochondral tissue constructs, using protocols that replicate some aspects of natural mesodermal development. For engineering of human bone, we discuss some of the current advances, and highlight the use of perfusion bioreactors for supporting anatomically exact human bone grafts.

Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds.

In normal tissue repair, macrophages exhibit a pro-inflammatory phenotype (M1) at early stages and a pro-healing phenotype (M2) at later stages. We have previously shown that M1 macrophages initiate angiogenesis while M2 macrophages promote vessel maturation. Therefore, we reasoned that scaffolds that promote sequential M1 and M2 polarization of infiltrating macrophages should result in enhanced angiogenesis and healing.

The role of macrophage phenotype in vascularization of tissue engineering scaffolds.

Angiogenesis is crucial for the success of most tissue engineering strategies. The natural inflammatory response is a major regulator of vascularization, through the activity of different types of macrophages and the cytokines they secrete. Macrophages exist on a spectrum of diverse phenotypes, from "classically activated" M1 to "alternatively activated" M2 macrophages.

Effects of detergent β-octylglucoside and phosphate salt solutions on phase behavior of monoolein mesophases.

Using small-angle x-ray scattering (SAXS), we investigated the phase behavior of mesophases of monoolein (MO) mixed with additives commonly used for the crystallization of membrane proteins from lipidic mesophases. In particular, we examined the effect of sodium and potassium phosphate salts and the detergent β-octylglucoside (βOG) over a wide range of compositions relevant for the crystallization of membrane proteins in lipidic mesophases. We studied two types of systems: 1), ternary mixtures of MO with salt solutions above the hydration boundary; and 2), quaternary mixtures of MO with βOG and salt solutions over a wide range of hydration conditions.