Abstract

Tissue-engineered grafts may be useful in Anterior Cruciate Ligament (ACL) repair and provide a novel, alternative treatment to clinical complications of rupture, harvest site morbidity and biocompatibility associated with autografts, allografts and synthetic grafts. We successfully used supercritical carbon dioxide (Sc-CO2) technology for manufacturing a “smart” biomaterial scaffold, which retains the native protein conformation and tensile strength of the natural ACL but is decellularized for a decreased immunogenic response. We designed and fabricated a new scaffold exhibiting (1) high tensile strength and biomechanical properties comparable to those of the native tissue, (2) thermodynamically-stable extra-cellular matrix (ECM), (3) preserved collagen composition and crosslinking, (4) a decellularized material milieu with potential for future engineering applications and (5) proven feasibility and biocompatibility in an animal model of ligament reconstruction. Because of the “smart” material ECM, this scaffold may have the potential for providing a niche and for directing stem cell growth, differentiations and function pertinent to new tissue formation. Sc-CO2-related technology is advanced and has the capability to provide scaffolds of high strength and durability, which sustain a lifetime of wear and tear under mechanical loading in vivo.

Highlights

  • Tissue-engineered grafts may be useful in Anterior Cruciate Ligament (ACL) repair and provide a novel, alternative treatment to clinical complications of rupture, harvest site morbidity and biocompatibility associated with autografts, allografts and synthetic grafts

  • Tendon allografts for ACL repair are gaining popularity worldwide, as their safety and efficacy continue to ­improve[33]

  • Increased risks of revision have been reported with the use of allografts, irrespective of whether the grafts were processed with chemicals or with low- or high-dose ­irradiation[34,35]

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Summary

Introduction

Tissue-engineered grafts may be useful in Anterior Cruciate Ligament (ACL) repair and provide a novel, alternative treatment to clinical complications of rupture, harvest site morbidity and biocompatibility associated with autografts, allografts and synthetic grafts. Tissue maturation post-implantation and, sometimes, have caused knee joint inflammation as a result of the innate immune response to foreign b­ odies[10] These clinical needs and challenges have prompted biomedical researchers to consider tissue engineering approaches in order to produce a biocompatible ACL implant exhibiting long-term durability in vivo[1,11]. The “perfect” biomaterial for implant prostheses needs to: (1) be biodegradable and non-toxic in its complete form and its degradation products; (2) have similar biomechanical properties as the replaced native tissue; (3) promote cell functions pertinent to new tissue formation including attachment, migration, production of ECM, etc.; (4) be a substrate for bioactive chemical compounds (such as enzymes, medications, growth factors); (5) exhibit high angiogenic potential with low immunogenicity and low thrombogenicity; (6) be malleable for processing into various sizes, geometric forms and structures; and (7) ideally possess high information content like the E­ CM14

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