Review
Biomimetic approach to tissue engineering

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Abstract

The overall goal of tissue engineering is to create functional tissue grafts that can regenerate or replace our defective or worn out tissues and organs. Examples of grafts that are now in pre-clinical studies or clinical use include engineered skin, cartilage, bone, blood vessels, skeletal muscle, bladder, trachea, and myocardium. Engineered tissues are also finding applications as platforms for pharmacological and physiological studies in vitro. To fully mobilize the cell's biological potential, a new generation of tissue engineering systems is now being developed to more closely recapitulate the native developmental milieu, and mimic the physiologic mechanisms of transport and signaling. We discuss the interactions between regenerative biology and engineering, in the context of (i) creation of functional tissue grafts for regenerative medicine (where biological input is critical), and (ii) studies of stem cells, development and disease (where engineered tissues can serve as advanced 3D models).

Section snippets

“Biomimetic” approach to tissue engineering

Tissue development and remodeling in living organisms is orchestrated by cascades of regulatory factors interacting at multiple levels, in space and time. Whole animal models certainly provide biologic fidelity (at least within given species), but offer limited control over the local environment, and limited real-time insight. In contrast, traditional cell culture provides significant control over the cellular environment along with precise insight into cellular processes, but at the expense of

Biomaterial scaffolds for guiding tissue organization

Scaffold materials – native or synthetic, permanent or biodegradable – are processed into 3D architectures suitable for cell seeding and cultivation. Material choices are guided by the need to restore cell signaling and to match the mechanical behavior of the tissue being engineered. Scaffolds also serve as “informational templates” to the cells, by implementing patterning, binding of ligands, and sustained release of cytokines [1]. Each tissue poses its own challenges to scaffold design, and

Environmental control of nutrients and metabolites

The critical parameter for cell survival in native and engineered tissues is oxygen (due to its low solubility in plasma and culture medium). In native tissues, oxygen is supplied by vascular networks, over short diffusional transport distances and with the utilization of hemoglobin that increases the total oxygen content of blood. In conventional tissue engineering approaches, tissue constructs are just immersed in culture medium. Diffusional transport of oxygen under these conditions can

Complex tissues

Tissue engineering has largely utilized “minimalistic” approaches based on homogenous populations of cells provided with suitable environmental conditions to give rise to specific practical outcomes (e.g., mineralized scaffolds or contractile tissues). However, only a few tissue types are derived from single-cell populations. Bone, for example, is in a constant state of flux, based on interactions of osteocytes, osteoblasts and osteoclasts. Both the bone and cardiac tissues are highly

Summary

By faithfully recapitulating the tissue context in vitro, we would create realistic experimental models that can be used to better understand developmental and regenerative processes. Because of the complex and dynamic nature of cell responses to regulatory signals, non-invasive (longitudinal) imaging of engineered constructs during cultivation would greatly advance our ability to study cellular responses to micro-environmental parameters with spatial and temporal specificity. The selection of

Acknowledgments

The authors gratefully acknowledge research support by the National Institutes of Health (HL076485, DE16525 and EB002520 to G.V.-N.) and Canada Foundation for Innovation (Leaders Opportunity Fund to M.R.).

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