Biologic and Synthetic Implants to Replace the Anterior Cruciate Ligament (original) (raw)
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ACL reconstruction using a novel hybrid scaffold composed of polyarylate fibers and collagen fibers
Journal of Biomedical Materials Research Part A, 2012
The objective was to perform an initial in vivo evaluation of a novel braided hybrid polyarylate and collagen fiber scaffold for the reconstruction of the anterior cruciate ligament (ACL). The braided hybrid scaffold is composed of 75% poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate)(12,10), [p(DTD DD)] fibers and 25% type I bovine collagen fibers. The scaffold is designed to temporarily bear mechanical loads and gradually degrade as neoligament tissue is deposited. Scaffolds were electron beam sterilized and used to reconstruct the ACL in five Finnish Dorset crossed-bred sheep in this feasibility study. At 4 (n ¼ 1) and 12 (n ¼ 4) weeks post-op, scaffolds were retrieved and analyzed for cellular ingrowth and strength retention. There was extensive cell infiltration and vascularity, which increased with time. Tissue ingrowth occurred throughout the cross section in the midsubstance of the scaffolds. After 12 weeks all scaffolds were intact. Femur-scaffold-tibia complex (FSTC) explanted at 12 weeks had a yield load of 42 6 22 N and a stiffness of 9 6 3 N mm À1. All scaffolds were well tolerated in the intraarticular space and induced tissue ingrowth, including new blood vessels, fibroblasts, inflammatory cells, and newly deposited collagen, throughout the cross section of the scaffold. Tissue ingrowth is critical to the success of a degradable scaffold for ACL reconstruction. Long-term studies in a large animal model are required to determine the efficacy of these novel hybrid scaffolds for ACL reconstruction. V
Bioengineering
The anterior cruciate ligament (ACL) of the knee joint is one of the strongest ligaments of the body and is often the target of traumatic injuries. Unfortunately, its healing potential is limited, and the surgical options for its replacement are frequently associated with clinical issues. A bioengineered ACL (bACL) was developed using a collagen matrix, seeded with autologous cells and successfully grafted and integrated into goat knee joints. We hypothesize that, in order to reduce the cost and simplify the model, an acellular bACL can be used as a substitute for a torn ACL, and bone plugs can be replaced by endobuttons to fix the bACL in situ. First, acellular bACLs were successfully grafted in the goat model with 18% recovery of ultimate tensile strength 6 months after implantation (94 N/mm2 vs. 520). Second, a bACL with endobuttons was produced and tested in an exvivo bovine knee model. The natural collagen scaffold of the bACL contributes to supporting host cell migration, grow...
Journal of Visualized Experiments, 2014
Injury to the ACL is a commonly encountered problem in active individuals. Even partial tears of this intra-articular knee ligament lead to biomechanical deficiencies that impair function and stability. Current options for the treatment of partial ACL tears range from nonoperative, conservative management to multiple surgical options, such as: thermal modification, single-bundle repair, complete reconstruction, and reconstruction of the damaged portion of the native ligament. Few studies, if any, have demonstrated any single method for management to be consistently superior, and in many cases patients continue to demonstrate persistent instability and other comorbidities. The goal of this study is to identify a potential cell source for utilization in the development of a tissue engineered patch that could be implemented in the repair of a partially torn ACL. A novel protocol was developed for the expansion of cells derived from patients undergoing ACL reconstruction. To isolate the cells, minced hACL tissue obtained during ACL reconstruction was digested in a Collagenase solution. Expansion was performed using DMEM/F12 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (P/ S). The cells were then stored at-80 ºC or in liquid nitrogen in a freezing medium consisting of DMSO, FBS and the expansion medium. After thawing, the hACL derived cells were then seeded onto a tissue engineered scaffold, PLAGA (Poly lactic-co-glycolic acid) and control Tissue culture polystyrene (TCPS). After 7 days, SEM was performed to compare cellular adhesion to the PLAGA versus the control TCPS. Cellular morphology was evaluated using immunofluorescence staining. SEM (Scanning Electron Microscope) micrographs demonstrated that cells grew and adhered on both PLAGA and TCPS surfaces and were confluent over the entire surfaces by day 7. Immunofluorescence staining showed normal, non-stressed morphological patterns on both surfaces. This technique is promising for applications in ACL regeneration and reconstruction.
The Potential for Primary Repair of the ACL
Sports Medicine and Arthroscopy Review, 2011
The objective of this work is to assess the feasibility of successfully repairing the torn ACL. Two major motivators for developing a new treatment for ACL injuries are the recently reported high rates of osteoarthritis after conventional ACL reconstruction as well as the problem of how to safely treat skeletally immature patients. A key factor in developing such a technique was the identification of the main inhibitor of intrinsic ACL healing -the lack of clot formation between the two torn ends of the ligament. A bioactive and biocompatible scaffold which could be placed in the wound site to enhance cellular proliferation and biosynthesis was developed. This biomaterial has shown promising functional outcomes in several large animal models of primary repair of partial and complete ACL transection over 4 to 14 weeks, suggesting potential for a successful, future clinical application.
Potential of Skin Fibroblasts for Application to Anterior Cruciate Ligament Tissue Engineering
Cell Transplantation, 2011
Fibroblasts isolated from skin and from anterior cruciate ligament (ACL) secrete type I and type III collagens in vivo and in vitro. However, it is much easier and practical to obtain a small skin biopsy than an ACL sample to isolate fibroblasts for tissue engineering applications. Various tissue engineering strategies have been proposed for torn ACL replacement. We report here the results of the implantation of bioengineered ACLs (bACLs), reconstructed in vitro using a type I collagen scaffold, anchored with two porous bone plugs to allow bone-ligament-bone surgical engraftment. The bACLs were seeded with autologous living dermal fibroblasts, and grafted for 6 months in goat knee joints. Histological and ultrastructural observations ex vivo demonstrated a highly organized ligamentous structure, rich in type I collagen fibers and cells. Grafts' vascularization and innervation were observed in all bACLs that were entirely reconstructed in vitro. Organized Sharpey's fibers and fibrocartilage, including chondrocytes, were present at the osseous insertion sites of the grafts. They showed remodeling and matrix synthesis postimplantation. Our tissue engineering approach may eventually provide a new solution to replace torn ACL in humans.
Journal of Biomedical Materials Research Part A, 2009
The purpose of this study is to evaluate the phenotypic responses of human anterior cruciate ligament (ACL) cells on two biodegradable materials: poly(e-caprolactone) (PCL) and chitosan. ACL cells cultured on PCL displayed phenotypes that were well spread with a developed cytoskeleton. In comparison, chitosan was not an appropriate substrate to support the attachment and spreading of ACL cells, which was attributed to the low fibronectin (FN) adsorption of chitosan. However, ACL cells cultured on chitosan exhibited a dramatic effect on increasing transcripts of transforming growth factor b1 (TGF b1) and collagen III. After coating FN on chitosan surface, cell morphology and the mRNA levels of all tested genes had the similar levels on PCL and FN-coated chitosan. This indicates the expression of TGF b1 and collagen III mRNA of human ACL cells was seem to correlate closely with the adhesion behavior of human ACL cells and was influenced by the underlying substrate properties. Since an ideal scaffold used in ACL tissue engineering is not only for cell attachment but also for extracellular matrix deposition during ligament regeneration, chitosan may be considered as a scaffold for ACL tissue engineering, which can upregulate the expression of specific genes of matrix production and wound healing in human ACL cells to synthesize more quantity of FN and TGF b1 proteins.
Use of ultra-high molecular weight polycaprolactone scaffolds for ACL reconstruction
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2015
Previously, we reported on the implantation of electrospun polycaprolactone (PCL) grafts for use in ACL tissue engineering in a small animal model. In the present study, we hypothesized that grafts fabricated from ultra-high molecular weight polycaprolactone (UHMWPCL) would have similarly favorable biologic properties but superior mechanical properties as compared to grafts fabricated from PCL. Two forms of polycaprolactone were obtained (UHMWPCL, MW= 500 kD, and PCL, MW= 80 kD) and electrospun into scaffolds that were used to perform ACL reconstruction in 7-8 week old male Lewis rats. The following groups were examined: UHMWPCL, PCL, flexor digitorum longus (FDL) allograft, native ACL, as well as sham surgery in which the ACL was transsected. At 16 weeks post-operatively, biomechanical testing, histology, and immunohistochemistry (IHC) were performed. Analysis of cellularity indicated that there was no significant difference among the UHMWPCL, PCL, and FDL allograft groups. Quantif...