From microscaled capillaries to millimeter‐sized vessels, human vasculature spans multiple scales and cell types. The convergence of bioengineering, materials science, and stem cell biology has ...enabled tissue engineers to recreate the structure and function of different hierarchical levels of the vascular tree. Engineering large‐scale vessels aims to replace damaged arteries, arterioles, and venules and their routine application in the clinic may become a reality in the near future. Strategies to engineer meso‐ and microvasculature are extensively explored to generate models for studying vascular biology, drug transport, and disease progression as well as for vascularizing engineered tissues for regenerative medicine. However, bioengineering tissues for transplantation has failed to result in clinical translation due to the lack of proper integrated vasculature for effective oxygen and nutrient delivery. The development of strategies to generate multiscale vascular networks and their direct anastomosis to host vasculature would greatly benefit this formidable goal. In this review, design considerations and technologies for engineering millimeter‐, meso‐, and microscale vessels are discussed. Examples of recent state‐of‐the‐art strategies to engineer multiscale vasculature are also provided. Finally, key challenges limiting the translation of vascularized tissues are identified and perspectives on future directions for exploration are presented.
Engineering human vasculature, ranging from large blood vessels to capillaries, is discussed here, with a specific focus on design criteria, bioengineering approaches, and key challenges for generating millimeter‐to‐microscale vasculature and transplantable vascularized tissues.
Some of the most significant leaps in the history of modern civilization-the development of article in China, the steam engine, which led to the European industrial revolution, and the era of ...computers-have occurred when science converged with engineering. Recently, the convergence of human pluripotent stem cell technology with biomaterials and bioengineering have launched a new medical innovation: functional human engineered tissue, which promises to revolutionize the treatment of failing organs including most critically, the heart. This compendium covers recent, state-of-the-art developments in the fields of cardiovascular tissue engineering, as well as the needs and challenges associated with the clinical use of these technologies. We have not attempted to provide an exhaustive review in stem cell biology and cardiac cell therapy; many other important and influential reports are certainly merit but already been discussed in several recent reviews. Our scope is limited to the engineered tissues that have been fabricated to repair or replace components of the heart (eg, valves, vessels, contractile tissue) that have been functionally compromised by diseases or developmental abnormalities. In particular, we have focused on using an engineered myocardial tissue to mitigate deficiencies in contractile function.
Organs-on-a-chip (OOCs) are miniature tissues and organs grown in vitro that enable modeling of human physiology and disease. The technology has emerged from converging advances in tissue ...engineering, semiconductor fabrication, and human cell sourcing. Encompassing innovations in human stem cell technology, OOCs offer a promising approach to emulate human patho/physiology in vitro, and address limitations of current cell and animal models. Here, we review the design considerations for single and multi-organ OOCs, discuss remaining challenges, and highlight the potential impact of OOCs as a fast-track opportunity for tissue engineering to advance drug development and precision medicine.
Ronaldson-Bouchard and Vunjak-Novakovic discuss the design considerations for single and multi-organ organs-on-a-chip (OOCs) and highlight the potential impact of OOCs as a fast-track opportunity for tissue engineering to advance drug development and precision medicine.
We explore the utility of bioengineered human tissues—individually or connected into physiological units—for biological research. While much smaller and simpler than their native counterparts, these ...tissues are complex enough to approximate distinct tissue phenotypes: molecular, structural, and functional. Unlike organoids, which form spontaneously and recapitulate development, “organs-on-a-chip” are engineered to display some specific functions of whole organs. Looking back, we discuss the key developments of this emerging technology. Thinking forward, we focus on the challenges faced to fully establish, validate, and utilize the fidelity of these models for biological research.
Organ-on-a-chip technologies promise to bridge a long-standing gap between animal models and in vivo human studies, but several challenges remain for making this technology broadly utilizable.
Abstract Tissue-engineered regeneration of a failing human heart remains a major challenge, while cardiovascular disease continues to take more lives than all cancers combined. Much has been learned ...from the basic and clinical studies, with the most interesting developments happening at the interfaces of disciplines. This seems to be the right time to step back and rethink the evolving paradigm of tissue engineering, and to reflect about the most promising directions to take. We clearly need new therapeutic modalities that are effective and yet simple enough to be practical, and the field is looking into the therapeutic potential of stem-progenitor cells, cardiac and vascular, that are enabled by bioactive factors and functionalized biomaterials.
Myocardial tissue engineering: in vitro models Vunjak Novakovic, Gordana; Eschenhagen, Thomas; Mummery, Christine
Cold Spring Harbor perspectives in medicine,
03/2014, Letnik:
4, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Modeling integrated human physiology in vitro is a formidable task not yet achieved with any of the existing cell/tissue systems. However, tissue engineering is becoming increasingly successful at ...authentic representation of the actual environmental milieu of tissue development, regeneration and disease progression, and in providing real-time insights into morphogenic events. Functional human tissue units engineered to combine biological fidelity with the high-throughput screening and real-time measurement of physiological responses are poised to transform drug screening and predictive modeling of disease. In this review, we focus on the in vitro engineering of functional human myocardium that mimics heart tissue for analysis of myocardial function, in the context of physiological studies, drug screening for therapeutics, and safety pharmacology.
Abstract 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. First, decellularized meniscus ECM hydrogel retained tissue-specific proteoglycans and collagens, and significantly upregulated expression of fibrochondrogenic markers by hMSCs versus collagen hydrogel alone in vitro . The meniscus ECM hydrogel in turn supported delivery of hMSCs for integrative repair of a full-thickness defect model in meniscal explants after in vitro culture and in vivo subcutaneous implantation. When applied to an orthotopic model of meniscal injury in nude rat, hMSCs in meniscus ECM hydrogel were retained out to eight weeks post-injection, contributing to tissue regeneration and protection from joint space narrowing, pathologic mineralization, and osteoarthritis development, as evidenced by macroscopic and microscopic image analysis. Based on these findings, we propose the use of tissue-specific meniscus ECM-derived hydrogel for the delivery of therapeutic hMSCs to treat meniscal injury.
Bone tissue engineering with human stem cells Marolt, Darja; Knezevic, Miomir; Novakovic, Gordana Vunjak
Stem cell research & therapy,
05/2010, Letnik:
1, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Treatment of extensive bone defects requires autologous bone grafting or implantation of bone substitute materials. An attractive alternative has been to engineer fully viable, biological bone grafts ...in vitro by culturing osteogenic cells within three-dimensional scaffolds, under conditions supporting bone formation. Such grafts could be used for implantation, but also as physiologically relevant models in basic and translational studies of bone development, disease and drug discovery. A source of human cells that can be derived in large numbers from a small initial harvest and predictably differentiated into bone forming cells is critically important for engineering human bone grafts. We discuss the characteristics and limitations of various types of human embryonic and adult stem cells, and their utility for bone tissue engineering.
Functional regeneration of complex large‐scaled defects requires both soft‐ and hard‐tissue grafts. Moreover, bone constructs within these grafts require an extensive vascular supply for survival and ...metabolism during the engraftment. Soft‐tissue pedicles are often used to vascularize bony constructs. However, extensive autologous tissue‐harvest required for the fabrication of these grafts remains a major procedural drawback. In the current work, a composite flap is fabricated using synthetic soft‐tissue matrices and decellularized bone, combined in vivo to form de novo composite tissue with its own vascular supply. Pre‐vascularization of the soft‐tissue matrix using dental pulp stem cells (DPSCs) and human adipose microvascular endothelial cells (HAMECs) enhances vascular development within decellularized bones. In addition, osteogenic induction of bone constructs engineered using adipose derived mesenchymal stromal cells positively affects micro‐capillary organization within the mineralized component of the neo‐tissue. Eventually, these neo‐tissues used as axial reconstructive flaps support long‐term bone defect repair, as well as muscle defect bridging. The composite flaps described here may help eliminate invasive autologous tissue‐harvest for patients in need of viable grafts for transplantation.
Large tissue defects necessitate autologous tissue harvest, perfused by a potent vascular network. In the current work, a composite neo‐tissue flap is fabricated from pre‐vascularized polymeric matrices and decellularized bones. By using high resolution in vivo imaging, the composite flaps are shown to support long‐term bone repair and vascularization, as well as soft‐tissue coverage.
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