Biomimetic tissue-engineered anterior cruciate ligament replacement

Abstract

There are >200,000 anterior cruciate ligament (ACL) ruptures each year in the United States, and, due to the poor healing properties of the ACL, surgical reconstruction with autograft or allograft tissue is the current treatment of these injuries. To regenerate the ACL, the ideal matrix should be biodegradable, porous, and exhibit sufficient mechanical strength to allow formation of neoligament tissue. Researchers have developed ACL scaffolds with collagen fibers, silk, biodegradable polymers, and composites with limited success. Our group has developed a biomimetic ligament replacement by using 3D braiding technology. In this preliminary in vivo rabbit model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regeneration with our cell-seeded, tissue-engineered ligament replacement.biomaterials ͉ regenerative medicine T his study was conducted to evaluate the performance of a polymeric 3D braided fibrous tissue-engineered anterior cruciate ligament (ACL) replacement for use in ACL reconstruction. The feasibility of this approach was investigated by comparison of cell-seeded and unseeded tissue-engineered ligaments (TELs) with a rabbit model. The key concepts investigated were (i) the in vivo response of allograft cells seeded onto TELs, (ii) the effect of porosity and pore interconnectivity on cell and collagen infiltration, (iii) the capability of the implant to allow for vascularization, and (iv) the capability of the implant to maintain mechanical function and to transfer load to the neoligament.Several groups have explored ligament-like scaffolds with collagen fibers, silk, biodegradable polymers and composites with limited success (1-6). During this study, we fabricated an absorbable polyL-lactide (PLLA) 3D, braided TEL replacement capable of supporting the growth and phenotypic expression of cells when seeded in vitro. There have been several published observations of favorable PLLA device interactions in animal and human clinical studies (2, 4, 7-10). The degradation of PLLA from a chemical standpoint in vivo can be categorized into five stages (2, 7). These stages are hydration, depolymerization, loss of mass integrity, absorption, and elimination. This polymer was chosen because of its mechanical retention and its in vitro cellular response to primary rabbit ACL cells (6,(11)(12)(13)(14).Rabbits are one of the most commonly used animals for orthopedic surgery in vivo studies (1,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Adult New Zealand White rabbits were used in this study because rabbits are relatively high-level vertebrates, having a size that enables surgical operations, convenient histology, and mechanical analysis. In addition, there was data on ACL reconstruction in rabbits with bone-patellar tendon-bone autografts (the gold standard for human reconstructions) that could be used to compare with our tissue engineered ligament results (20).The goal of this investigation was to develop and study a tissue-engineered ACL replacement that could e...

Three-Dimensional Engineered Bone–Ligament–Bone Constructs for Anterior Cruciate Ligament Replacement

“…For instance, Cooper et al (2007) has developed synthetic braided scaffolds as grafts for ACL repair. 51 Synthetic scaffolds are not needed in our method.…”

“…For instance, Cooper et al (2007) has developed synthetic braided scaffolds as grafts for ACL repair. 51 Synthetic scaffolds are not needed in our method. One of the disadvantages of using synthetic scaffold is that its degradation rates in vivo often exceed the desired rates.…”

Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

“…23 Novel weaving technologies have further refined the mechanical response of such constructs, and commercial products based on these approaches are making their way to market. [24][25][26][27] The approach that we and others have adopted for fiberreinforced tissue engineering builds on these past efforts, but focuses specifically on the multiscale rendering of fiber reinforcement from the nano-and micron-scale through to the tissue level. These efforts employ electrospinning of ultrafine or nanofibrous polymer networks as a base technology.…”

Development of a Cell Depositing System using Inkjet Technology

“…Another study found that a PLGA scaffold had a lower inflammatory response than a collagenbased hydrogel, while also showing higher integration with the host body [48]. PLLA has also been successfully engineered into an artificial anterior cruciate ligament [12].…”

“…For example, PLA scaffolds have characteristically rigid structures. While this scaffold would be appropriate for tissues like bone, tendons, and ligaments [70,12], this rigidity would not be appropriate for contractile tissues, such as cardiac tissue. Furthermore, traditional scaffold fabrication methods, such as casting and molding, often produce tissues that lack vascularization.…”