Effects of Endochondral and Intramembranous Ossification Pathways on Bone Tissue Formation and Vascularization in Human Tissue-Engineered Grafts.

Bone grafts can be engineered by differentiating human mesenchymal stromal cells (MSCs) via the endochondral and intramembranous ossification pathways. We evaluated the effects of each pathway on the properties of engineered bone grafts and their capacity to drive bone regeneration. Bone-marrow-derived MSCs were differentiated on silk scaffolds into either hypertrophic chondrocytes (hyper) or osteoblasts (osteo) over 5 weeks of in vitro cultivation, and were implanted subcutaneously for 12 weeks.

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.

Perfusion Enhances Hypertrophic Chondrocyte Matrix Deposition, But Not the Bone Formation.

Perfusion bioreactors have been an effective tool in bone tissue engineering. Improved nutrient delivery and the application of shear forces have stimulated osteoblast differentiation and matrix production, allowing for generation of large, clinically sized constructs. Differentiation of hypertrophic chondrocytes has been considered an alternative strategy for bone tissue engineering.

Tissue Engineered Bone Differentiated From Human Adipose Derived Stem Cells Inhibit Posterolateral Fusion in an Athymic Rat Model.

Study Design: Biological augmentation spinal arthrodesis trial in athymic rats.

Objective: To assess the efficacy of tissue-engineered bone to promote L4-L5 intertransverse process fusion in an athymic rat model.

Summary Of Background Data: Each year in the United States, over 400,000 spinal fusion surgeries are performed requiring bone graft.

Tissue-engineered hypertrophic chondrocyte grafts enhanced long bone repair.

Bone has innate ability to regenerate following injury. However, large and complex fractures exceed bone's natural repair capacity and result in non-unions, requiring external intervention to facilitate regeneration. One potential treatment solution, tissue-engineered bone grafts, has been dominated by recapitulating intramembranous ossification (bone formation by osteoblasts), although most serious bone injuries heal by endochondral ossification (bone formation by remodeling of hypertrophic cartilaginous anlage).

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.

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.

Tissue-engineered autologous grafts for facial bone reconstruction.

Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care-the use of bone harvested from another region in the body-has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins.

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.

Should we use cells, biomaterials, or tissue engineering for cartilage regeneration?

For a long time, cartilage has been a major focus of the whole field of tissue engineering, both because of the constantly growing need for more effective options for joint repair and the expectation that this apparently simple tissue will be easy to engineer. After several decades, cartilage regeneration has proven to be anything but easy. With gratifying progress in our understanding of the factors governing cartilage development and function, and cell therapy being successfully used for several decades, there is still a lot to do.

Synthesis and characterization of an aggrecan mimic.

Aggrecan (AGG) is a large, aggregating proteoglycan present throughout the body, but predominantly found in articular cartilage. The principle features of AGG, its hyaluronan (HA) binding domain and its abundance of covalently attached glycosaminoglycans (GAGs), make it an essential component of the functional ability of articular cartilage. Current tissue engineering constructs have attempted to stimulate AGG production, but have been unable to produce adequate amounts of mature AGG, and hence have suffered a mismatch in mechanical properties.