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Xue R, Wong J, Imere A, King H, Clegg P, Cartmell S. Current clinical opinion on surgical approaches and rehabilitation of hand flexor tendon injury-a questionnaire study. FRONTIERS IN MEDICAL TECHNOLOGY 2024; 6:1269861. [PMID: 38425421 PMCID: PMC10902169 DOI: 10.3389/fmedt.2024.1269861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 01/31/2024] [Indexed: 03/02/2024] Open
Abstract
The management of flexor tendon injury has seen many iterations over the years, but more substantial innovations in practice have been sadly lacking. The aim of this study was to investigate the current practice of flexor tendon injury management, and variation in practice from the previous reports, most troublesome complications, and whether there was a clinical interest in potential innovative tendon repair technologies. An online survey was distributed via the British Society for Surgery of the Hand (BSSH) and a total of 132 responses were collected anonymously. Results showed that although most surgeons followed the current medical recommendation based on the literature, a significant number of surgeons still employed more conventional treatments in clinic, such as general anesthesia, ineffective tendon retrieval techniques, and passive rehabilitation. Complications including adhesion formation and re-rupture remained persistent. The interest in new approaches such as use of minimally invasive instruments, biodegradable materials and additive manufactured devices was not strong, however the surgeons were potentially open to more effective and economic solutions.
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Affiliation(s)
- Ruikang Xue
- Department of Materials, Faculty of Science and Engineering, School of Natural Sciences, University of Manchester, Manchester, United Kingdom
| | - Jason Wong
- Division of Cell Matrix Biology & Regenerative Medicine, University of Manchester, Manchester, United Kingdom
- Department of Plastic & Reconstructive Surgery, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | - Angela Imere
- Department of Materials, Faculty of Science and Engineering, School of Natural Sciences, University of Manchester, Manchester, United Kingdom
- The Henry Royce Institute, Royce Hub Building, The University of Manchester, Manchester, United Kingdom
| | - Heather King
- Addos Consulting Ltd, Winchester, United Kingdom
| | - Peter Clegg
- Department and of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, William Henry Duncan Building, University of Liverpool, Liverpool, United Kingdom
- MRC-Versus Arthritis Centre for Integrated Research in Musculoskeletal Ageing, William Henry Duncan Building, University of Liverpool, Liverpool, United Kingdom
| | - Sarah Cartmell
- Department of Materials, Faculty of Science and Engineering, School of Natural Sciences, University of Manchester, Manchester, United Kingdom
- The Henry Royce Institute, Royce Hub Building, The University of Manchester, Manchester, United Kingdom
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Hahn J, Gögele C, Schulze-Tanzil G. Could an Anterior Cruciate Ligament Be Tissue-Engineered from Silk? Cells 2023; 12:2350. [PMID: 37830564 PMCID: PMC10571837 DOI: 10.3390/cells12192350] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/14/2023] Open
Abstract
Silk has a long history as an exclusive textile, but also as a suture thread in medicine; nowadays, diverse cell carriers are manufactured from silk. Its advantages are manifold, including high biocompatibility, biomechanical strength and processability (approved for nearly all manufacturing techniques). Silk's limitations, such as scarcity and batch to batch variations, are overcome by gene technology, which allows for the upscaled production of recombinant "designed" silk proteins. For processing thin fibroin filaments, the sericin component is generally removed (degumming). In contrast to many synthetic biomaterials, fibroin allows for superior cell adherence and growth. In addition, silk grafts demonstrate superior mechanical performance and long-term stability, making them attractive for anterior cruciate ligament (ACL) tissue engineering. Looking at these promising properties, this review focusses on the responses of cell types to silk variants, as well as their biomechanical properties, which are relevant for ACL tissue engineering. Meanwhile, sericin has also attracted increasing interest and has been proposed as a bioactive biomaterial with antimicrobial properties. But so far, fibroin was exclusively used for experimental ACL tissue engineering approaches, and fibroin from spider silk also seems not to have been applied. To improve the bone integration of ACL grafts, silk scaffolds with osteogenic functionalization, silk-based tunnel fillers and interference screws have been developed. Nevertheless, signaling pathways stimulated by silk components remain barely elucidated, but need to be considered during the development of optimized silk cell carriers for ACL tissue engineering.
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Affiliation(s)
- Judith Hahn
- Workgroup BioEngineering, Institute of Polymer Materials, Leibniz-Institut für Polymerforschung Dresden e.V. (IPF), Hohe Straße 6, 01069 Dresden, Germany;
| | - Clemens Gögele
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany;
| | - Gundula Schulze-Tanzil
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany;
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3
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Kokozidou M, Gögele C, Pirrung F, Hammer N, Werner C, Kohl B, Hahn J, Breier A, Schröpfer M, Meyer M, Schulze-Tanzil G. In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams. Histochem Cell Biol 2023; 159:275-292. [PMID: 36309635 PMCID: PMC10006054 DOI: 10.1007/s00418-022-02156-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/16/2022] [Indexed: 11/30/2022]
Abstract
Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or F combined with the foam (F + coll). Cell-free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, cell vitality and content, histo(patho)logy of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed.Scaffolds did not affect mice weight development and organs, indicating no organ toxicity. Moreover, scaffolds maintained their size and shape and reflected a high cell viability prior to and following implantation. Coll or F + coll scaffolds seeded with cells yielded superior macroscopic properties compared to the controls. Mild signs of inflammation (foreign-body giant cells and hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable after explantation, elastic modulus, maximum force, tensile strength and strain at Fmax were significantly lower in explanted scaffolds compared to those before implantation, with no significant differences between scaffold subtypes, except for a higher maximum force in F + coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering. a Lapine anterior cruciate ligament (LACL): red arrow, posterior cruciate ligament: yellow arrow. Medial anterior meniscotibial ligament: black arrow. b Explant culture to isolate LACL fibroblasts. c Scaffold variants: co: controls; F: functionalization by gas-phase fluorination; coll: collagen foam cross-linked with hexamethylene diisocyanate (HMDI). c1-2 Embroidery pattern of the scaffolds. d Scaffolds were seeded with LACL fibroblasts using a dynamical culturing approach as depicted. e Scaffolds were implanted subnuchally into nude mice, fixed at the nuchal ligament and sacrospinal muscle tendons. f Two weeks after implantation. g Summary of analyses performed. Scale bars 1 cm (b, d), 0.5 cm (c). (sketches drawn by G.S.-T. using Krita 4.1.7 [Krita foundation, The Netherlands]).
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Affiliation(s)
- Maria Kokozidou
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419, Nuremberg, Germany
| | - Clemens Gögele
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419, Nuremberg, Germany.,Department of Biosciences and Medical Biology, Paris Lodron University Salzburg, Hellbrunnerstraße 34, 5020, Salzburg, Austria
| | - Felix Pirrung
- Division of Macroscopic and Clinical Anatomy, Gottfried Schatz Research Center, Medical University of Graz, Harrachgasse 21, 8010, Graz, Austria
| | - Niels Hammer
- Division of Macroscopic and Clinical Anatomy, Gottfried Schatz Research Center, Medical University of Graz, Harrachgasse 21, 8010, Graz, Austria.,Department of Orthopedic and Trauma Surgery, University of Leipzig, Leipzig, Germany.,Fraunhofer Institute for Machine Tools and Forming Technology IWU, Nöthnitzer Straße 44, 01187, Dresden, Germany
| | - Christian Werner
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419, Nuremberg, Germany
| | - Benjamin Kohl
- Department of Traumatology and Reconstructive Surgery, Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Zu Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany
| | - Judith Hahn
- Workgroup Bio-Engineering, Department Materials Engineering, Leibniz-Institut für Polymerforschung Dresden e. V. (IPF), Institute Polymers Materials, Hohe Straße 6, 01069, Dresden, Germany
| | - Annette Breier
- Workgroup Bio-Engineering, Department Materials Engineering, Leibniz-Institut für Polymerforschung Dresden e. V. (IPF), Institute Polymers Materials, Hohe Straße 6, 01069, Dresden, Germany
| | - Michaela Schröpfer
- FILK Freiberg Institute gGmbH (FILK), Meißner Ring 1-5, 09599, Freiberg, Germany
| | - Michael Meyer
- FILK Freiberg Institute gGmbH (FILK), Meißner Ring 1-5, 09599, Freiberg, Germany
| | - Gundula Schulze-Tanzil
- Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419, Nuremberg, Germany.
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Uquillas JA, Spierings J, van der Lande A, Eren AD, Bertrand M, Yuan H, Yuan H, van Groningen B, Janssen R, Ito K, de Boer J, Foolen J. An off-the-shelf decellularized and sterilized human bone-ACL-bone allograft for anterior cruciate ligament reconstruction. J Mech Behav Biomed Mater 2022; 135:105452. [PMID: 36122497 DOI: 10.1016/j.jmbbm.2022.105452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 08/31/2022] [Accepted: 09/03/2022] [Indexed: 11/16/2022]
Abstract
Approximately 1% of active individuals participating in sports rupture their anterior cruciate ligaments (ACL) every year, which is currently reconstructed using tendon autografts. Upon reconstruction, clinical issues of concern are ACL graft rupture, persistent knee instability, limited return to sports, and early onset of osteoarthritis (OA). This happens because tendon autografts do not have the same compositional, structural, and mechanical properties as a native ACL. To overcome these problems, we propose to use decellularized bone-ACL-bone allografts in ACL reconstruction (ACLR) as a mechanically robust, biocompatible, and immunologically safe alternative to autografts. Here, a decellularization protocol combined with sterilization using supercritical carbon dioxide (scCO2) was used to thoroughly decellularize porcine and human ACLs attached to tibial and femoral bone blocks. The specimens were named ultrACLean and their compositional, structural, and mechanical properties were determined. Our results indicate that: 1) decellularization of ultrACLean allografts leads to the removal of nearly 97% of donor cells, 2) ultrACLean has mechanical properties which are not different to native ACL, 3) ultrACLean maintained similar collagen content and decreased GAG content compared to native ACL, and 4) ultrACLean is not cytotoxic to seeded tendon-derived cells in vitro. Results from an in vivo pilot experiment showed that ultrACLean is biocompatible and elicits a moderate immunological response. In summary, ultrACLean has proven to be a mechanically competent and biocompatible graft with the potential to be used in ACLR surgery.
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Affiliation(s)
- Jorge Alfredo Uquillas
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands
| | - Janne Spierings
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands
| | - Antonio van der Lande
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands
| | - Aysegul Dede Eren
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands
| | - Manon Bertrand
- Hightech Contract Manufacturing Medical, Nijmegen, the Netherlands
| | - Hao Yuan
- Huipin Yuan's Lab, Sichuan, China
| | | | - Bart van Groningen
- Department of Orthopaedic Surgery, Maxima Medical Centre Eindhoven/Veldhoven, the Netherlands
| | - Rob Janssen
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Department of Orthopaedic Surgery, Maxima Medical Centre Eindhoven/Veldhoven, the Netherlands; Health Innovations and Technology, Department of Paramedical Sciences, Fontys University of Applied Sciences, Eindhoven, the Netherlands
| | - Keita Ito
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Eindhoven MedTech Innovation Center, Eindhoven University of Technology, Eindhoven, the Netherlands
| | - Jan de Boer
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands
| | - Jasper Foolen
- Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Institute of Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.
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Teuschl AH, Tangl S, Heimel P, Schwarze UY, Monforte X, Redl H, Nau T. Osteointegration of a Novel Silk Fiber-Based ACL Scaffold by Formation of a Ligament-Bone Interface. Am J Sports Med 2019; 47:620-627. [PMID: 30653344 DOI: 10.1177/0363546518818792] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Given the unsatisfactory results and reported drawbacks of anterior cruciate ligament (ACL) reconstruction, such as donor site morbidity and the limited choice of grafts in revision surgery, new regenerative approaches based on tissue-engineering strategies are currently under investigation. PURPOSES To determine (1) if a novel silk fiber-based ACL scaffold is able to initiate osteointegration in the femoral and tibial bone tunnels under in vivo conditions and (2) if the osteointegration process will be improved by intraoperatively seeding the scaffolds with the autologous stromal vascular fraction, an adipose-derived, stem cell-rich isolate from knee fat pads. STUDY DESIGN Controlled laboratory study. METHODS A total of 33 sheep underwent ACL resection and were then randomly assigned to 2 experimental groups: ACL reconstruction with a scaffold alone and ACL reconstruction with a cell-seeded scaffold. Half of the sheep in each group were randomly chosen and euthanized 6 months after surgery and the other half at 12 months. To analyze the integration of the silk-based scaffold in the femoral and tibial bone tunnels, hard tissue histology and micro-computed tomography measurements were performed. RESULTS Hard tissue histological workup showed that in all treatment groups, with or without the application of the autologous stromal vascular fraction, an interzone of collagen fibers had formed between bone and silk-based graft. This collagen-fiber continuity partly consisted of Sharpey fibers, comparable with tendon-bone healing known for autografts and allografts. Insertion sites were more broad based at 6 months and more concentrated on the slightly protruding, bony knoblike structures at 12 months. Histologically, no differences between the treatment groups were detectable. Analysis of micro-computed tomography measurements revealed a significantly higher tissue density for the cell-seeded scaffold group as compared with the scaffold-alone group in the tibial but not femoral bone tunnel after 12 months of implantation. CONCLUSION The novel silk fiber-based scaffold for ACL regeneration demonstrated integration into the bone tunnels via the formation of a fibrous interzone similar to allografts and autografts. Histologically, additional cell seeding did not enhance osteointegration. No significant differences between 6 and 12 months could be detected. After 12 months, there was still a considerable amount of silk present, and a longer observation period is necessary to see if a true ligament-bone enthesis will be formed. CLINICAL RELEVANCE ACL regeneration with a silk fiber-based scaffold with and without additional cell seeding may provide an alternative treatment option to current techniques of surgical reconstruction.
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Affiliation(s)
- Andreas Herbert Teuschl
- Department of Life Science Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Stefan Tangl
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
- Core Facility Hard Tissue and Biomaterial Research, Karl Donath Laboratory, School of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Patrick Heimel
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria
| | - Uwe Yacine Schwarze
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
- Core Facility Hard Tissue and Biomaterial Research, Karl Donath Laboratory, School of Dentistry, Medical University of Vienna, Vienna, Austria
| | - Xavier Monforte
- Department of Life Science Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Heinz Redl
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria
| | - Thomas Nau
- Austrian Cluster for Tissue Regeneration, Vienna, Austria
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria
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Petrillo S, Papalia R, Maffulli N, Volpi P, Denaro V. Osteoarthritis of the hip and knee in former male professional soccer players. Br Med Bull 2018; 125:121-130. [PMID: 29385409 DOI: 10.1093/bmb/ldy001] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Accepted: 01/01/2018] [Indexed: 12/20/2022]
Abstract
BACKGROUND Professional soccer (PS) players are at great risk of osteoarthritis (OA) of the knee and hip. SOURCES OF DATA Following the PRISMA guidelines, the key words 'osteoarthritis' and 'soccer' or 'football' were matched with 'players' or 'former' or 'retired' and with 'hip' or 'knee' on December 24, 2017 in the following databases: PubMed, Cochrane, Google scholar, Embase and Ovid. Only comparative studies reporting the prevalence rate of OA of both hip and knee joint in former PS athletes (fPSa) and age and sex matched controls were considered. AREAS OF AGREEMENT In fPSa, the prevalence rate of OA of both hip and knee is significantly higher compared to age and sex matched controls. AREAS OF CONTROVERSY The pathological pathways responsible for the development of OA of the hip and knee in PS athletes (PSa) are still not clearly understood. GROWING POINTS The prevalence rate of clinical OA of the hip was 8.6% in fPSa and 5.6% in controls (odd ratio (OR) = 1.5; 95% CI: 1.06-2.31). The radiographic rate of OA was 21.2% in fPSa and 9.8% in controls (OR = 2.4; 95% CI: 1.66-3.69). A total of 14.6 and 53.7% of fPSa presented clinical and radiographic signs of OA of the knee, respectively, vs 12.9% (OR = 1.16; 95% CI: 0.86-1.55) and 31.9% (OR = 2.47; 95% CI: 2.03-3.00) of controls. Sonographic evidence of OA of the knee was found in 52% of fPSa and 33% of controls (OR = 2.2; 95% CI: 1.24-3.89). AREAS TIMELY FOR DEVELOPING RESEARCH Preventive training programmes should be developed to reduce the number of fPSa presenting early OA.
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Affiliation(s)
- Stefano Petrillo
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
| | - Rocco Papalia
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
| | - Nicola Maffulli
- Department of Musculoskeletal Disorders, University of Salerno School of Medicine and Surgery, Via Giovanni Paolo II, 132 - 84084 Fisciano, Salerno, Italy.,Centre for Sports and Exercise Medicine, Barts and The London School of Medicine and Dentistry, Mile End Hospital, 275 Bancroft Road, London E1 4DG, England
| | - Piero Volpi
- Knee Surgery and Sports Traumatology Unit, Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Vincenzo Denaro
- Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy
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Waryasz GR, Marcaccio S, Gil JA, Owens BD, Fadale PD. Anterior Cruciate Ligament Repair and Biologic Innovations. JBJS Rev 2017; 5:e2. [DOI: 10.2106/jbjs.rvw.16.00050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Teuschl A, Heimel P, Nürnberger S, van Griensven M, Redl H, Nau T. A Novel Silk Fiber-Based Scaffold for Regeneration of the Anterior Cruciate Ligament: Histological Results From a Study in Sheep. Am J Sports Med 2016; 44:1547-57. [PMID: 26957219 DOI: 10.1177/0363546516631954] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Because of ongoing problems with anterior cruciate ligament (ACL) reconstruction, new approaches in the treatment of ACL injuries, particularly strategies based on tissue engineering, have gained increasing research interest. To allow for ACL regeneration, a structured scaffold that provides a mechanical basis, has cells from different sources, and comprises mechanical as well as biological factors is needed. Biological materials, biodegradable polymers, and composite materials are being used and tested as scaffolds. The optimal scaffold for ACL regeneration should be biocompatible and biodegradable to allow tissue ingrowth but also needs to have the right mechanical properties to provide immediate mechanical stability. HYPOTHESES The study hypotheses were that (1) a novel degradable silk fiber-based scaffold with mechanical properties similar to the native ACL will be able to initiate ligament regeneration after ACL resection and reconstruction under in vivo conditions and (2) additional cell seeding of the scaffold with autologous stromal vascular fraction-containing adipose-derived stem cells will increase regenerative activity. STUDY DESIGN Controlled laboratory study. METHODS A total of 33 mountain sheep underwent ACL resection and randomization to 2 experimental groups: (1) ACL reconstruction with a scaffold alone and (2) ACL reconstruction with a cell-seeded scaffold. Histological evaluation of the intra-articular portion of the reconstructed/regenerated ligament was performed after 6 and 12 months. RESULTS After 6 months, connective tissue surrounded the silk scaffold with ingrowth in some areas. The cell-seeded scaffolds had a significant lower silk content compared with the unseeded scaffolds and demonstrated a higher content of newly formed tissue. After 12 months, the density of the silk fibers decreased significantly, and the ingrowth of newly formed tissue increased in both groups. No differences between the 2 groups regarding silk fiber degradation and regenerated tissue were detected at 12 months. CONCLUSION The novel silk fiber-based scaffold was able to stimulate ACL regeneration under in vivo conditions. Additional cell seeding led to increased tissue regeneration and decreased silk fiber content at 6 months, whereas these differences were not present at 12 months. CLINICAL RELEVANCE ACL regeneration using a silk fiber-based scaffold with and without additional cell seeding may provide a new treatment option after joint injuries.
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Affiliation(s)
- Andreas Teuschl
- Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Patrick Heimel
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria Karl Donath Laboratory for Hard Tissue and Biomaterial Research, Medical University of Vienna, Vienna, Austria
| | - Silvia Nürnberger
- Austrian Cluster for Tissue Regeneration, Vienna, Austria Department of Traumatology, Medical University of Vienna, Vienna, Austria
| | - Martijn van Griensven
- Department of Experimental Trauma Surgery, Technical University of Munich, Munich, Germany
| | - Heinz Redl
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria Austrian Cluster for Tissue Regeneration, Vienna, Austria
| | - Thomas Nau
- Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Vienna, Austria Austrian Cluster for Tissue Regeneration, Vienna, Austria
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9
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Hahner J, Hoyer M, Hillig S, Schulze-Tanzil G, Meyer M, Schröpfer M, Lohan A, Garbe LA, Heinrich G, Breier A. Diffusion chamber system for testing of collagen-based cell migration barriers for separation of ligament enthesis zones in tissue-engineered ACL constructs. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2015; 26:1085-99. [PMID: 26300365 DOI: 10.1080/09205063.2015.1076714] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
A temporary barrier separating scaffold zones seeded with different cell types prevents faster growing cells from overgrowing co-cultured cells within the same construct. This barrier should allow sufficient nutrient diffusion through the scaffold. The aim of this study was to test the effect of two variants of collagen-based barriers on macromolecule diffusion, viability, and the spreading efficiency of primary ligament cells on embroidered scaffolds. Two collagen barriers, a thread consisting of a twisted film tape and a sponge, were integrated into embroidered poly(lactic-co-caprolactone) and polypropylene scaffolds, which had the dimension of lapine anterior cruciate ligaments (ACL). A diffusion chamber system was designed and established to monitor nutrient diffusion using fluorescein isothiocyanate-labeled dextran of different molecular weights (20, 40, 150, 500 kDa). Vitality of primary lapine ACL cells was tested at days 7 and 14 after seeding using fluorescein diacetate and ethidium bromide staining. Cell spreading on the scaffold surface was measured using histomorphometry. Nuclei staining of the cross-sectioned scaffolds revealed the penetration of ligament cells through both barrier types. The diffusion chamber was suitable to characterize the diffusivity of dextran molecules through embroidered scaffolds with or without integrated collagen barriers. The diffusion coefficients were generally significantly lower in scaffolds with barriers compared to those without barriers. No significant differences between diffusion coefficients of both barrier types were detected. Both barriers were cyto-compatible and prevented most of the ACL cells from crossing the barrier, whereby the collagen thread was easier to handle and allowed a higher rate of cell spreading.
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Affiliation(s)
- J Hahner
- a Leibniz-Institut für Polymerforschung, Institute of Polymer Materials , Hohe Straße 6, 01069 Dresden , Germany
| | - M Hoyer
- b Central Laboratory , DRK Manniske-Hospital , An der Wipper 2, 06567 Bad Frankenhausen , Germany.,c Department of Bioanalytics , Technical University , Seestraße 13, 13353 Berlin , Germany
| | - S Hillig
- a Leibniz-Institut für Polymerforschung, Institute of Polymer Materials , Hohe Straße 6, 01069 Dresden , Germany
| | - G Schulze-Tanzil
- d Institute of Anatomy , Paracelsus Medical University , Salzburg and Nuremberg, Prof. Ernst Nathan Straße 1, 90340 Nuremberg , Germany.,e Department of Trauma and Reconstructive Surgery , Charité-Universitätsmedizin Berlin , Campus Benjamin Franklin, Garystrasse 5, 14195 Berlin , Germany
| | - M Meyer
- f Research Institute of Leather and Plastic Sheeting - FILK , Meißner Ring 1-5, 09599 Freiberg , Germany
| | - M Schröpfer
- f Research Institute of Leather and Plastic Sheeting - FILK , Meißner Ring 1-5, 09599 Freiberg , Germany
| | - A Lohan
- g Forschungseinrichtungen für Experimentelle Medizin, Charité-Universitätsmedizin Berlin , Campus Benjamin Franklin, Kramerstr.6-10, 12207 Berlin , Germany
| | - L-A Garbe
- c Department of Bioanalytics , Technical University , Seestraße 13, 13353 Berlin , Germany
| | - G Heinrich
- a Leibniz-Institut für Polymerforschung, Institute of Polymer Materials , Hohe Straße 6, 01069 Dresden , Germany.,h Institute of Materials Science , Technische Universität Dresden , Helmholtzstraße 10, 01062 Dresden , Germany
| | - A Breier
- a Leibniz-Institut für Polymerforschung, Institute of Polymer Materials , Hohe Straße 6, 01069 Dresden , Germany
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Nau T, Redl H, Teuschl AH. Comment on: In Vivo Evaluation of Electrospun Polycaprolactone Graft for Anterior Cruciate Ligament Engineering. Tissue Eng Part A. 2015;21(7-8):1228-1236. Tissue Eng Part A 2015; 21:2775. [PMID: 26239874 DOI: 10.1089/ten.tea.2015.0257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Thomas Nau
- 1 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center , Vienna, Austria .,2 The Austrian Cluster for Tissue Regeneration
| | - Heinz Redl
- 1 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center , Vienna, Austria .,2 The Austrian Cluster for Tissue Regeneration
| | - Andreas Herbert Teuschl
- 1 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center , Vienna, Austria .,2 The Austrian Cluster for Tissue Regeneration.,3 Department of Biochemical Engineering, University of Applied Sciences Technikum Wien , Vienna, Austria
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Dlaska CE, Andersson G, Brittberg M, Suedkamp NP, Raschke MJ, Schuetz MA. Clinical Translation in Tissue Engineering—The Surgeon’s View. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s40610-015-0013-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Moradi M, Hood B, Moradi M, Atala A. The potential role of regenerative medicine in the man-agement of traumatic patients. J Inj Violence Res 2015; 7:27-35. [PMID: 25618439 PMCID: PMC4288293 DOI: 10.5249/jivr.v7i1.704] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 12/13/2014] [Indexed: 11/10/2022] Open
Abstract
Traumatic injury represents the most common cause of death in ages 1 to 44 years and a significant proportion of patients treated in hospital emergency wards each year. Unfortunately, for patients who survive their injuries, survival is not equal to complete recovery. Many traumatic injuries are difficult to treat with conventional therapy and result in permanent disability. In such situations, regenerative medicine has the potential to play an important role in recovery of function. Regenerative medicine is a field that seeks to maintain or restore function with the development of biological substitutes for diseased or damaged tissues. Several regenerative approaches are currently under investigation, with a few achieving clinical application. For example, engineered skin has gained FDA approval, and more than 20 tissue engineered skin substitutes are now commercially available. Other organ systems with promising animal models and small human series include the central and peripheral nervous systems, the musculoskeletal system, the respiratory and genitourinary tracts, and others. This paper will be a clinically oriented review of the regenerative approaches currently under investigation of special interest to those caring for traumatic patients.
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Affiliation(s)
| | | | | | - Anthony Atala
- Department of Urology, Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC,USA.
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Nau T, Teuschl A. Regeneration of the anterior cruciate ligament: Current strategies in tissue engineering. World J Orthop 2015; 6:127-136. [PMID: 25621217 PMCID: PMC4303781 DOI: 10.5312/wjo.v6.i1.127] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Revised: 06/19/2014] [Accepted: 07/29/2014] [Indexed: 02/06/2023] Open
Abstract
Recent advancements in the field of musculoskeletal tissue engineering have raised an increasing interest in the regeneration of the anterior cruciate ligament (ACL). It is the aim of this article to review the current research efforts and highlight promising tissue engineering strategies. The four main components of tissue engineering also apply in several ACL regeneration research efforts. Scaffolds from biological materials, biodegradable polymers and composite materials are used. The main cell sources are mesenchymal stem cells and ACL fibroblasts. In addition, growth factors and mechanical stimuli are applied. So far, the regenerated ACL constructs have been tested in a few animal studies and the results are encouraging. The different strategies, from in vitro ACL regeneration in bioreactor systems to bio-enhanced repair and regeneration, are under constant development. We expect considerable progress in the near future that will result in a realistic option for ACL surgery soon.
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Embroidered polymer-collagen hybrid scaffold variants for ligament tissue engineering. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2014; 43:290-9. [PMID: 25175216 DOI: 10.1016/j.msec.2014.07.010] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/08/2014] [Revised: 05/03/2014] [Accepted: 07/02/2014] [Indexed: 01/14/2023]
Abstract
Embroidery techniques and patterns used for scaffold production allow the adaption of biomechanical scaffold properties. The integration of collagen into embroidered polylactide-co-caprolactone [P(LA-CL)] and polydioxanone (PDS) scaffolds could stimulate neo-tissue formation by anterior cruciate ligament (ACL) cells. Therefore, the aim of this study was to test embroidered P(LA-CL) and PDS scaffolds as hybrid scaffolds in combination with collagen hydrogel, sponge or foam for ligament tissue engineering. ACL cells were cultured on embroidered P(LA-CL) and PDS scaffolds without or with collagen supplementation. Cell adherence, vitality, morphology and ECM synthesis were analyzed. Irrespective of thread size, ACL cells seeded on P(LA-CL) scaffolds without collagen adhered and spread over the threads, whereas the cells formed clusters on PDS and larger areas remained cell-free. Using the collagen hydrogel, the scaffold colonization was limited by the gel instability. The collagen sponge layers integrated into the scaffolds were hardly penetrated by the cells. Collagen foams increased scaffold colonization in P(LA-CL) but did not facilitate direct cell-thread contacts in the PDS scaffolds. The results suggest embroidered P(LA-CL) scaffolds as a more promising basis for tissue engineering an ACL substitute than PDS due to superior cell attachment. Supplementation with a collagen foam presents a promising functionalization strategy.
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Kalaci A, Uruc V, Özden R, Gökhan Duman I, Dogramaci Y, Karapinar S, Yaldiz M. The Biocompatibility of Nitinol in Knee Joint Spaces and Femoral Tunnels: An Experimental Study in Rats. J HARD TISSUE BIOL 2014. [DOI: 10.2485/jhtb.23.317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Stępien-Słodkowska M, Ficek K, Eider J, Leońska-Duniec A, Maciejewska-Karłowska A, Sawczuk M, Zarębska A, Jastrzębski Z, Grenda A, Kotarska K, Cięszczyk P. The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish skiers with anterior cruciate ligament injury. Biol Sport 2013; 30:57-60. [PMID: 24744467 PMCID: PMC3944561 DOI: 10.5604/20831862.1029823] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/07/2012] [Indexed: 11/30/2022] Open
Abstract
Objectives The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study. Methods A total of 138 male recreational skiers with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury. DNA samples extracted from the oral epithelial cells were genotyped for the +1245G/T polymorphisms using real-time PCR method. Results Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p = 0.2469 and p = 0.33, respectively). There was a significant difference in the genotype distribution between skiers and controls (p = 0.045, Fisher's exact test). There was no statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher's exact test). Conclusions The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.
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Affiliation(s)
- M Stępien-Słodkowska
- University of Szczecin, Department of Physical Culture and Health Promotion, Szczecin, Poland
| | - K Ficek
- University of Szczecin, Department of Physical Culture and Health Promotion, Szczecin, Poland ; Galen Medical Center, Bieruń, Poland
| | - J Eider
- University of Szczecin, Department of Physical Culture and Health Promotion, Szczecin, Poland
| | - A Leońska-Duniec
- University of Szczecin, Department of Physical Culture and Health Promotion, Szczecin, Poland ; Academy of Physical Education and Sport, Department of Sport Education, Gdańsk, Poland
| | - A Maciejewska-Karłowska
- University of Szczecin, Department of Physical Culture and Health Promotion, Szczecin, Poland ; University of Szczecin, Department of Genetics, Poland
| | - M Sawczuk
- University of Szczecin, Department of Physical Culture and Health Promotion, Szczecin, Poland ; University of Szczecin, Department of Genetics, Poland
| | - A Zarębska
- Academy of Physical Education and Sport, Department of Sport Education, Gdańsk, Poland
| | - Z Jastrzębski
- Academy of Physical Education and Sport, Department of Sport Education, Gdańsk, Poland
| | - A Grenda
- West Pomeranian Technological University, Department of Physical Education and Sport, Szczecin, Poland
| | - K Kotarska
- University of Szczecin, Department of Physical Culture and Health Promotion, Szczecin, Poland
| | - P Cięszczyk
- Academy of Physical Education and Sport, Department of Sport Education, Gdańsk, Poland
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