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      Safety of Intra-Articular Use of Atelocollagen for Enhanced Tissue Repair

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          Abstract

          Collagen is an important biomaterial in intra-articular tissue engineering, but there are unanswered questions about its safety. We hypothesize that the addition of type-I-collagen for primary repair of the Anterior Cruciate Ligament (ACL) might result in a local and systemic reaction in a porcine model after 15 weeks as demonstrated by joint effusion, synovial thickening, elevated intraarticular and systemic leukocyte counts. Further, this reaction might be aggravated by the addition of a platelet concentrate. Eighteen porcine ACLs were transected and repaired with either sutures (n=6), a collagen sponge (n=6), or a collagen-platelet-composite (CPC; n=6). Twelve intact contralateral knees served as controls (n=12). No significant synovial thickening or joint effusion was seen in the collagen-treated knees. Synovial fluid leukocyte counts showed no significant differences between surgically treated and intact knees, and no differences were seen in leukocyte counts of the peripheral blood. The addition of a platelet concentrate to the knee joint resulted in lower serum levels of IL-1β, but serum levels of TNF-α were not significantly different between groups. In conclusion, the presence of collagen, with or without added platelets, did not increase the local or systemic inflammatory reactions following surgery, suggesting that Type I collagen is safe to use in the knee joint.

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          Most cited references45

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          Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates?

          Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this third article, we investigate the immune features of this biomaterial. During PRF processing, leucocytes could also secrete cytokines in reaction to the hemostatic and inflammatory phenomena artificially induced in the centrifuged tube. We therefore undertook to quantify 5 significant cell mediators within platelet poor plasma supernatant and PRF clot exudate serum: 3 proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), an antiinflammatory cytokine (IL-4), and a key growth promoter of angiogenesis (VEGF). Our data are correlated with that obtained in plasma (nonactivated blood) and in sera (activated blood). These initial analyses revealed that PRF could be an immune regulation node with inflammation retrocontrol abilities. This concept could explain the reduction of postoperative infections when PRF is used as surgical additive.
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            Collagen scaffolds for tissue engineering.

            There are two major approaches to tissue engineering for regeneration of tissues and organs. One involves cell-free materials and/or factors and one involves delivering cells to contribute to the regeneraion process. Of the many scaffold materials being investigated, collagen type I, with selective removal of its telopeptides, has been shown to have many advantageous features for both of these approaches. Highly porous collagen lattice sponges have been used to support in vitro growth of many types of tissues. Use of bioreactors to control in vitro perfusion of medium and to apply hydrostatic fluid pressure has been shown to enhance histogenesis in collagen scaffolds. Collagen sponges have also been developed to contain differentiating-inducing materials like demineralized bone to stimulate differentiation of cartilage tissue both in vitro and in vivo.
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              Antigenicity and immunogenicity of collagen.

              Pertinent issues of collagen antigenicity and immunogenicity are concisely reviewed as they relate to the design and application of biomedical devices. A brief discussion of the fundamental concepts of collagen immunochemistry is presented, with a subsequent review of documented clinical responses to devices containing reconstituted soluble or solubilized collagen. The significance of atelocollagen, concerns regarding collagen-induced autoimmunity, and other relevant topics are also addressed in the context of current understanding of the human immune response to collagen. (c) 2004 Wiley Periodicals, Inc.
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                Author and article information

                Journal
                Open Orthop J
                Open Orthop J
                TOORTHJ
                The Open Orthopaedics Journal
                Bentham Open
                1874-3250
                15 June 2012
                2012
                : 6
                : 231-238
                Affiliations
                [1 ]Department of Orthopaedic Surgery, Children’s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
                [2 ]Department of Radiology, Children’s Hospital Boston, 300 Longwood Ave, Boston, MA 02115, USA
                Author notes
                [* ]Address correspondence to this author at the Department of Orthopaedic Surgery, Children’s Hospital of Boston, 300 Longwood Ave, Boston, MA 02115, USA; Tel: 617 355 7497; Fax: 617 730 0459; E-mail: Martha.murray@ 123456childrens.harvard.edu
                Article
                TOORTHJ-6-231
                10.2174/1874325001206010231
                3395883
                22802918
                653cd7ae-b655-4a0a-9e6d-924cffcb7a77
                © Magarian et al.; Licensee Bentham Open.

                This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 11 November 2011
                : 18 April 2012
                : 21 April 2012
                Categories
                Article

                Orthopedics
                biomaterials,acl,safety,collagen,tissue engineering.
                Orthopedics
                biomaterials, acl, safety, collagen, tissue engineering.

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