Regenerative engineering and advanced materials science
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Introduction Musculoskeletal injuries arise largely from traumatic events, disease, and birth defects. Collectively, 30–40 million musculoskeletal repair and regenerative surgeries are performed in the United States each year. In some instances of severe injury, the diseased or damaged tissues and limb are surgically removed, with 135,000 new amputations performed each year. There are approximately 1.25 million amputees living in the United States, and they are largely between 41 and 70 years of age, with 75% of the procedures performed in those over age 65.1–7 The loss of function that results due to limb disease or its removal accounts for a significant number of clinical disorders, resulting in great social and economic cost. The successful restoration of tissue and organ function, especially for musculoskeletal tissues, is quantified by the generation and transmission of mechanical forces that facilitate simple and complex limb movement. Tissues such as bone, muscle, ligament, tendon, and cartilage are highly specialized both in composition and structure, providing a unique functionality that requires the selection of an optimal biomaterial and implant design. The characteristics of musculoskeletal tissues such as mechanical loading, viscoelastic properties, maintenance and differentiation of stem cells, sequestration of multiple chemical factors, and vasculature, are parameters that must be taken into consideration when developing engineered tissue substrates to augment and regenerate multiscale tissues.
The challenge moving forward is to understand the developmental complexities found in nature and translate this deep understanding into clinically successful strategies. For instance, we must learn from organisms such as newts and salamanders, for which a chopped limb is completely regenerated and functional within a period of 10 weeks.8 The limb is a complex organ consisting of various specialized tissues, and the challenge is to regenerate multiple tissues (bone, muscle, tendon, blood vessels, nerves, skin) simultaneously into a single integrated and functioning organ. As we pursue these challenges, we must pay attention to the fact that the regenerative capacity is inversely related to complexity of the organism. Human beings possess some limited regenerative capabilities, and surgeons are able to surgically reattach severed appendages that heal almost completely under specific conditions. A key strategy is to utilize biomaterials and engineered substrates as guides that can influence phenotype maturation of undifferentiated cell types through chemical and biophysical cues. This methodology known as “tissue engineering” (TE) seeks to restore the function of diseased or damaged tissues and organs using cues to promote the proliferation and phenotype development of donor cells. It is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function.9 To date, few engineered substrates have
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