Tissue Engineering

Augusto Zani, MD, Lina Antounians, MD
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Introduction

The generation of living tissue has long fueled the imagination - from Prometheus of Greek mythology to Mary Shelley’s Frankenstein. The first glimpse of regenerative medicine came with the use of skin grafts in Germany in the 1860s [1]. Virchow then recognized that tissue regeneration and healing was dependent on cellular proliferation - a vital component of classical tissue engineering. In vitro cell culture was first attempted by Ljunggren and Jolly in 1898 with the first active growth of cells (neurons) in culture reported by Harrison in 1910 [2].

Transplantation of larger organs though was dependent on the development of microsurgery and vascular anastomoses, described in vitro by Carrel in 1911 [3]. Ullman performed the first kidney transplant in an animal model which was followed by the first successful human kidney transplantation between identical twins by Merrill in 1956 [4]. The culmination was the first heart transplant by Barnard in 1967 [5]. While the term tissue engineering had been used to describe a variety of regenerative or restorative techniques, it is now defined as the “application of the principles and methods of engineering and life sciences toward the fundamental understanding of structure-function relationships in normal and pathologic mammalian tissue and the development of biological substitutes to restore, maintain or improve function” [6].

An initial attempt at tissue engineered cartilage by Green in the 1970s using chondrocytes seeded on a bone scaffold was unsuccessful but laid the conceptual framework of growing cells on a scaffold [1]. Skin substitutes for coverage of burn wounds were developed independently by Burke and Yannas, Green and Bell using fibroblasts and/or keratinocytes seeded on various scaffolds [7][8][9]. However, it was the pioneering work performed by Vacanti and Langer in the late 1980’s and early 1990’s that is often referenced as the true beginning of this new discipline [10][11].

The Tissue Engineering Society was founded in 1994 by Charles and Joseph Vacanti and has now expanded into the Tissue Engineering and Regenerative Medicine International Society (TERMIS). To aid and promote the exchange of information, the journal Tissue Engineering was founded in 1994 by Charles Vacanti and Antonio Mikos [12]. A survey of the editorial board in 2007 assessed strategically important concepts to further advancement of the field, with control of angiogenesis and stem cell science identified as key areas of future research[13]. As public awareness increased, from Vacanti’s “auriculosaurus” (mouse with a human ear-shaped scaffold implanted on its back) to Dolly (first mammalian clone from an adult cell) to the isolation of embryonic stem cells, tissue engineering has alternately fascinated and appalled[14][15]. Titles like “Who Plays God in the 21st Century?” emphasize the delicate balance that tissue engineers must maintain in their search for cures to some of medicine’s most difficult challenges.

What are the main goals of tissue engineering?

According to the National Institute of Biomedical Imaging and Bioengineering, there are three main goals of tissue engineering: to maintain, improve, or replace damaged tissues or organs. Ideally, cells could be harvested from a patient, grown or manipulated in vitro on a specially designed scaffold, and re-implanted in an autologous fashion to address both the underlying disorder while limiting the risk of rejection.

Why is tissue engineering particularly appealing for pediatric patients?

A key difference between pediatric and adult patients is the need to account for patient growth over time. Traditional implants, such as stents or synthetic patches, when used in pediatric patients can result in undesirable outcomes (e.g. chest deformation with patch repair of congenital diaphragmatic hernia) or increased risk of failure requiring re-operation (e.g valve replacement during repair of congenital heart disease). Tissue engineering presents an opportunity to develop implants that integrate and grow with the patient’s own tissues.

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Introduction

The generation of living tissue has long fueled the imagination - from Prometheus of Greek mythology to Mary Shelley’s Frankenstein. The first glimpse of regenerative medicine came with the use of skin grafts in Germany in the 1860s [1]. Virchow then recognized that tissue regeneration and healing was dependent on cellular proliferation - a vital component of classical tissue engineering. In vitro cell culture was first attempted by Ljunggren and Jolly in 1898 with the first active growth of cells (neurons) in culture reported by Harrison in 1910 [2].

Transplantation of larger organs though was dependent on the development of microsurgery and vascular anastomoses, described in vitro by Carrel in 1911 [3]. Ullman performed the first kidney transplant in an animal model which was followed by the first successful human kidney transplantation between identical twins by Merrill in 1956 [4]. The culmination was the first heart transplant by Barnard in 1967 [5]. While the term tissue engineering had been used to describe a variety of regenerative or restorative techniques, it is now defined as the “application of the principles and methods of engineering and life sciences toward the fundamental understanding of structure-function relationships in normal and pathologic mammalian tissue and the development of biological substitutes to restore, maintain or improve function” [6].

An initial attempt at tissue engineered cartilage by Green in the 1970s using chondrocytes seeded on a bone scaffold was unsuccessful but laid the conceptual framework of growing cells on a scaffold [1]. Skin substitutes for coverage of burn wounds were developed independently by Burke and Yannas, Green and Bell using fibroblasts and/or keratinocytes seeded on various scaffolds [7][8][9]. However, it was the pioneering work performed by Vacanti and Langer in the late 1980’s and early 1990’s that is often referenced as the true beginning of this new discipline [10][11].

The Tissue Engineering Society was founded in 1994 by Charles and Joseph Vacanti and has now expanded into the Tissue Engineering and Regenerative Medicine International Society (TERMIS). To aid and promote the exchange of information, the journal Tissue Engineering was founded in 1994 by Charles Vacanti and Antonio Mikos [12]. A survey of the editorial board in 2007 assessed strategically important concepts to further advancement of the field, with control of angiogenesis and stem cell science identified as key areas of future research[13]. As public awareness increased, from Vacanti’s “auriculosaurus” (mouse with a human ear-shaped scaffold implanted on its back) to Dolly (first mammalian clone from an adult cell) to the isolation of embryonic stem cells, tissue engineering has alternately fascinated and appalled[14][15]. Titles like “Who Plays God in the 21st Century?” emphasize the delicate balance that tissue engineers must maintain in their search for cures to some of medicine’s most difficult challenges.

What are the main goals of tissue engineering?

According to the National Institute of Biomedical Imaging and Bioengineering, there are three main goals of tissue engineering: to maintain, improve, or replace damaged tissues or organs. Ideally, cells could be harvested from a patient, grown or manipulated in vitro on a specially designed scaffold, and re-implanted in an autologous fashion to address both the underlying disorder while limiting the risk of rejection.

Why is tissue engineering particularly appealing for pediatric patients?

A key difference between pediatric and adult patients is the need to account for patient growth over time. Traditional implants, such as stents or synthetic patches, when used in pediatric patients can result in undesirable outcomes (e.g. chest deformation with patch repair of congenital diaphragmatic hernia) or increased risk of failure requiring re-operation (e.g valve replacement during repair of congenital heart disease). Tissue engineering presents an opportunity to develop implants that integrate and grow with the patient’s own tissues.

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Last updated: August 1, 2020