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Song Y, Che X, Wang Z, Li M, Zhang R, Wang D, Shi Q. A randomized trial of treatment for anterior cruciate ligament reconstruction by radial extracorporeal shock wave therapy. BMC Musculoskelet Disord 2024; 25:57. [PMID: 38216944 PMCID: PMC10787473 DOI: 10.1186/s12891-024-07177-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 01/05/2024] [Indexed: 01/14/2024] Open
Abstract
OBJECTIVE The aim of this study was to explore the effects of radial extracorporeal shock wave therapy (rESWT) in patients with anterior cruciate ligament(ACL) reconstruction(ACLR). METHODS We conducted a randomized, controlled trial involving 72 eligible patients with ACL reconstruction in which we compared two strategies: the experimental group was standard rehabilitation plus rESWT and the control group was standard rehabilitation plus sham rESWT. The outcome was the change from baseline to 24 weeks in the average score on Lysholm knee joint score (LKS), range of motion (ROM), visual analogue scale (VAS) and International Knee Literature Committee (IKDC). RESULTS Of 36 subjects assigned to rehabilitation plus rESWT, 4 lost to follow up. Of 36 assigned to rehabilitation plus sham rESWT, 5 lost to follow up. The LKS, ROM and IKDC scores of the experimental group were markedly increased at 3 and 6 weeks after treatment (P < 0.001), and the VAS was notably decreased (P < 0.001). However, there were no significant differences in the LKS, ROM, IKDC and VAS between the groups at 24 weeks after treatment (P > 0.05). CONCLUSION The strategy of rehabilitation plus rESWT had better functional outcomes after ACL reconstruction. As such, our study demonstrates that rESWT is essential for patients with ACL reconstruction. Early use of rESWT can improve joint function, pain relief and ability of daily living. rESWT has a positive effect on the overall rehabilitation of patients.
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Affiliation(s)
- Yufeng Song
- Second Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Xinle Che
- Shanxi Medical University, Taiyuan, 030001, China
| | - Zheyun Wang
- Shanxi Medical University, Taiyuan, 030001, China
| | - Mengshi Li
- Shanxi Medical University, Taiyuan, 030001, China
| | - Runjie Zhang
- Second Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Dongming Wang
- Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.
| | - Qiongfang Shi
- Department of Rehabilitation, Xinghualing District Central Hospital, Taiyuan, 030001, China
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Fortier LM, Hevesi M, Dasari SP, Mameri ES, Kerzner B, Khan ZA, Chahla J. Bridge-Enhanced Anterior Cruciate Ligament Repair for Mid-Substance Tear With Concomitant Lateral Meniscus Radial Repair. Arthrosc Tech 2022; 11:e1981-e1988. [PMID: 36457385 PMCID: PMC9705715 DOI: 10.1016/j.eats.2022.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 07/25/2022] [Indexed: 11/13/2022] Open
Abstract
In recent years, repair of the injured anterior cruciate ligament (ACL) has been subject to a renewed interest as novel arthroscopic techniques have been developed. Specifically, the bridge-enhanced ACL repair is a technique composed of a resorbable protein-based implant combined with autologous blood that is used to bridge the gap between 2 torn edges of a mid-substance ACL tear. This implant is believed to help facilitate healing of a primary suture repair and suture cinch and has since demonstrated noninferiority to ACL reconstruction with autograft at 2-year follow-up. The purpose of this Technical Note is to describe a step-by-step surgical technique of a mid-substance ACL repair using the bridge-enhanced ACL repair system in a case with a concomitant lateral meniscus radial repair.
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Affiliation(s)
| | - Mario Hevesi
- Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A
| | | | | | | | | | - Jorge Chahla
- Midwest Orthopaedics at Rush, Chicago, Illinois, U.S.A.,Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, Illinois, U.S.A.,Address correspondence to Jorge Chahla, M.D., Ph.D., Department of Orthopaedic Surgery, Rush University Medical Center, 1611 W. Harrison St., Suite 300, Chicago, IL 60612.
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3
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Tran DT, Guang Zhan Y, Tsai L. Dynamic tensile properties of porcine knee ligament. Biomed Mater Eng 2022; 33:293-302. [PMID: 35213341 DOI: 10.3233/bme-211318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND The knee plays an essential role in movement. There are four major ligaments in the knee which all have crucial functionalities for human activities. The anterior cruciate ligament (ACL) is the most commonly injured ligament in the knee, especially in athletes. OBJECTIVE The aim of this study was to investigate the dynamic tensile response of the porcine ACL at strain rates from 800 to 1500 s-1 for simulations of acute injury from sudden impact or collision. METHODS Split Hopkinson Tension Bar (SHTB) was utilized to create a dynamic tensile wave on the ACL. Stress-strain curves of strain rates between 800 s-1 to 1500 s-1 were recorded. RESULTS The results demonstrated that the elastic modulus of the porcine ACL at higher strain rates was six to eight times higher than that of porcine and human specimens at quasi-static strain rate. However, the failure stress was quite similar while the strain was much smaller than that at the lower strain rate. CONCLUSIONS ACL is highly strain rate sensitive and easier to break with lower failure strain when the strain rates increased to more than 1000 s-1. The stress-strain curves indicated that the sketching crimps at the slack region did not happen but switched to the sliding process of collagen fibers and was accompanied by some ruptures, which can develop into tears when strain and stress were large enough. On the other hand, the viscoelastic properties of the ligament, depending on the proteoglycan matrix and the cross-link, showed a limited value in the studied strain rate range.
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Affiliation(s)
- Dat Trong Tran
- Department of Mechanical Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan.,School of Transportation Engineering, Hanoi University of Science and Technology, Hanoi, Vietnam
| | - Yao Guang Zhan
- Department of Mechanical Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan
| | - Liren Tsai
- Department of Mechanical Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan
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4
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Chae S, Choi YJ, Cho DW. Mechanically and biologically promoted cell-laden constructs generated using tissue-specific bioinks for tendon/ligament tissue engineering applications. Biofabrication 2022; 14. [PMID: 35086074 DOI: 10.1088/1758-5090/ac4fb6] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 01/27/2022] [Indexed: 11/11/2022]
Abstract
Tendon and ligament tissues provide stability and mobility crucial for musculoskeletal function, but are particularly prone to injury. Owing to poor innate healing capacity, the regeneration of mature and functional tendon/ligament (T/L) poses a formidable clinical challenge. Advanced bioengineering strategies to develop biomimetic tissue implants are highly desired for the treatment of T/L injuries. Here, we presented a cell-based tissue engineering strategy to generate cell-laden tissue constructs comprising stem cells and tissue-specific bioinks using 3D cell-printing technology. We implemented an in vitro preconditioning approach to guide semi-organized T/L-like formation before the in vivo application of cell-printed implants. During in vitro maturation, tissue-specific decellularized extracellular matrix-based cellular constructs facilitated long-term in vitro culture with high cell viability and promoted tenogenesis with enhanced cellular/structural anisotropy. Moreover, we demonstrated improved cell survival/retention upon in vivo implantation of pre-matured constructs in nude mice with de novo tendon formation and improved mechanical strength. Although in vivo mechanical properties of the cell-printed implants were lower than those of human T/L tissues, the results of this study may have significant implications for future cell-based therapies in tendon and ligament regeneration and translational medicine.
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Affiliation(s)
- Suhun Chae
- Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Gyeongsangbuk-do, Pohang, Gyeongsangbuk-do, 37679, Korea (the Republic of)
| | - Yeong-Jin Choi
- Department of Advanced Biomaterials Research, Korea Institute of Materials Science, 797, Changwon-daero, Seongsan-gu, Gyeongsangnam-do, Changwon, 51508, Korea (the Republic of)
| | - Dong-Woo Cho
- Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, KOREA, Pohang, 37673, Korea (the Republic of)
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5
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Spindler KP, Imrey PB, Yalcin S, Beck GJ, Calbrese G, Cox CL, Fadale PD, Farrow L, Fitch R, Flanigan D, Fleming BC, Hulstyn MJ, Jones MH, Kaeding C, Katz JN, Kriz P, Magnussen R, McErlean E, Melgaard C, Owens BD, Saluan P, Strnad G, Winalski CS, Wright R. Design Features and Rationale of the BEAR-MOON (Bridge-Enhanced ACL Restoration Multicenter Orthopaedic Outcomes Network) Randomized Clinical Trial. Orthop J Sports Med 2022; 10:23259671211065447. [PMID: 35097143 PMCID: PMC8793429 DOI: 10.1177/23259671211065447] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 08/24/2021] [Indexed: 11/17/2022] Open
Abstract
Background: BEAR (bridge-enhanced anterior cruciate ligament [ACL] restoration), a paradigm-shifting technology to heal midsubstance ACL tears, has been demonstrated to be effective in a single-center 2:1 randomized controlled trial (RCT) versus hamstring ACL reconstruction. Widespread dissemination of BEAR into clinical practice should also be informed by a multicenter RCT to demonstrate exportability and compare efficacy with bone--patellar tendon–bone (BPTB) ACL reconstruction, another clinically standard treatment. Purpose: To present the design and initial preparation of a multicenter RCT of BEAR versus BPTB ACL reconstruction (the BEAR: Multicenter Orthopaedic Outcomes Network [BEAR-MOON] trial). Design and analytic issues in planning the complex BEAR-MOON trial, involving the US National Institute of Arthritis and Musculoskeletal and Skin Diseases, the US Food and Drug Administration, the BEAR implant manufacturer, a data and safety monitoring board, and institutional review boards, can usefully inform both clinicians on the trial’s strengths and limitations and future investigators on planning of complex orthopaedic studies. Study Design: Clinical trial. Methods: We describe the distinctive clinical, methodological, and operational challenges of comparing the innovative BEAR procedure with the well-established BPTB operation, and we outline the clinical motivation, experimental setting, study design, surgical challenges, rehabilitation, outcome measures, and planned analysis of the BEAR-MOON trial. Results: BEAR-MOON is a 6-center, 12-surgeon, 200-patient randomized, partially blinded, noninferiority RCT comparing BEAR with BPTB ACL reconstruction for treating first-time midsubstance ACL tears. Noninferiority of BEAR relative to BPTB will be claimed if the total score on the International Knee Documentation Committee (IKDC) subjective knee evaluation form and the knee arthrometer 30-lb (13.61-kg) side-to-side laxity difference are both within respective margins of 16 points for the IKDC and 2.5 mm for knee laxity. Conclusion: Major issues include patient selection, need for intraoperative randomization and treatment-specific postoperative physical therapy regimens (because of fundamental differences in surgical technique, initial stability construct, and healing), and choice of noninferiority margins for short-term efficacy outcomes of a novel intervention with evident short-term advantages and theoretical, but unverified, long-term benefits on other dimensions.
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Affiliation(s)
| | - Kurt P. Spindler
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Peter B. Imrey
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Sercan Yalcin
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Gerald J. Beck
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Gary Calbrese
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Charles L. Cox
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Paul D. Fadale
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Lutul Farrow
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Robert Fitch
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - David Flanigan
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Braden C. Fleming
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Michael J. Hulstyn
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Morgan H. Jones
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Christopher Kaeding
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Jeffrey N. Katz
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Peter Kriz
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Robert Magnussen
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Ellen McErlean
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Carrie Melgaard
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Brett D. Owens
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Paul Saluan
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Greg Strnad
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Carl S. Winalski
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
| | - Rick Wright
- BEAR-MOON Design Group: All authors are listed in the Authors section at the end of this article
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Controversies in the management of anterior cruciate ligament injuries in skeletally immature patients. CURRENT ORTHOPAEDIC PRACTICE 2022. [DOI: 10.1097/bco.0000000000001089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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7
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Tran DT, Juang YC, Tsai L. Contrary response of porcine articular cartilage below and over 1000 s -1. Clin Biomech (Bristol, Avon) 2021; 90:105506. [PMID: 34610506 DOI: 10.1016/j.clinbiomech.2021.105506] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 08/31/2021] [Accepted: 09/27/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Knee joints experience excessive loads quite frequently during sports activities, and these shocks could accelerate progressive degeneration in articular cartilage. METHODS Quasi-static and dynamic response of porcine knee articular cartilages were investigated in this research. Split Hopkinson Pressure Bars (SHPB) were utilized to examine the articular cartilage properties at strain rates between 0.01-2000 s-1. FINDINGS The results showed that strain rate is an important factor for articular cartilages, distinctively divided into above and below 1000 s-1. The articular cartilages exhibit a strain hardening phenomenon when shock loaded at strain rates under 1000 s-1. When loaded at strain rates over 1000 s-1, their ultimate strength and elastic modulus decreased with increasing strain rates. INTERPRETATION The biphasic structure of the cartilage explained the change of modulus. At the lower strain rates, fibers realigned and solidified the structure, while at higher strain rates, there is not enough time for the tissue fluid to move inside the cartilage, leading to a reduction in the deformability of the specimen and raising of Young's modulus. The results can be utilized to provide some useful data for biomaterial and computational works in the future.
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Affiliation(s)
- D T Tran
- National Kaohsiung University of Science and Technology, Department of Mechanical Engineering, No. 415, Jiangong rd., Kaohsiung, Taiwan
| | - Y C Juang
- National Kaohsiung University of Science and Technology, Department of Mechanical Engineering, No. 415, Jiangong rd., Kaohsiung, Taiwan
| | - L Tsai
- National Kaohsiung University of Science and Technology, Department of Mechanical Engineering, No. 415, Jiangong rd., Kaohsiung, Taiwan.
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8
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Barnett SC, Murray MM, Badger GJ, Yen YM, Kramer DE, Sanborn R, Kiapour A, Proffen B, Sant N, Fleming BC, Micheli LJ. Earlier Resolution of Symptoms and Return of Function After Bridge-Enhanced Anterior Cruciate Ligament Repair As Compared With Anterior Cruciate Ligament Reconstruction. Orthop J Sports Med 2021; 9:23259671211052530. [PMID: 34778483 PMCID: PMC8581796 DOI: 10.1177/23259671211052530] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 06/09/2021] [Indexed: 01/09/2023] Open
Abstract
Background: Bridge-enhanced anterior cruciate ligament repair (BEAR) has noninferior
patient-reported outcomes when compared with autograft anterior cruciate
ligament reconstruction (ACLR) at 2 years. However, the comparison of BEAR
and autograft ACLR at earlier time points—including important outcomes such
as resolution of knee pain and symptoms, recovery of strength, and return to
sport—has not yet been reported. Hypothesis: It was hypothesized that the BEAR group would have higher outcomes on the
International Knee Documentation Committee and Knee injury and
Osteoarthritis Outcome Score, as well as improved muscle strength, in the
early postoperative period. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 100 patients aged 13 to 35 years with complete midsubstance
anterior cruciate ligament injuries were randomized to receive a suture
repair augmented with an extracellular matrix implant (n = 65) or an
autograft ACLR (n = 35). Outcomes were assessed at time points up to 2 years
postoperatively. Mixed-model repeated-measures analyses were used to compare
BEAR and ACLR outcomes. Patients were unblinded after their 2-year
visit. Results: Repeated-measures testing revealed a significant effect of group on the
International Knee Documentation Committee Subjective Score
(P = .015), most pronounced at 6 months after surgery
(BEAR = 86 points vs ACLR = 78 points; P = .001). There was
a significant effect of group on the Knee injury and Osteoarthritis Outcome
Score-Symptoms subscale scores (P = .010), largely
attributed to the higher BEAR scores at the 1-year postoperative time point
(88 vs 82; P = .009). The effect of group on hamstring
strength was significant in the repeated-measures analysis
(P < .001), as well as at all postoperative time
points (P < .001 for all comparisons). At 1 year after
surgery, approximately 88% of the patients in the BEAR group and 76% of the
ACLR group had been cleared for return to sport (P =
.261). Conclusion: Patients undergoing the BEAR procedure had earlier resolution of symptoms and
increased satisfaction about their knee function, as well as improved
resolution of hamstring muscle strength throughout the 2-year follow-up
period. Registration: NCT02664545 (ClinicalTrials.gov identifier)
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Affiliation(s)
- Samuel C Barnett
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Martha M Murray
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA
| | | | | | - Yi-Meng Yen
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Dennis E Kramer
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Ryan Sanborn
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.,University of Vermont, Burlington, Vermont, USA.,Members of the BEAR Trial Team are listed in the Authors section at the end of this article.,Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Ata Kiapour
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.,University of Vermont, Burlington, Vermont, USA.,Members of the BEAR Trial Team are listed in the Authors section at the end of this article.,Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Benedikt Proffen
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.,University of Vermont, Burlington, Vermont, USA.,Members of the BEAR Trial Team are listed in the Authors section at the end of this article.,Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Nicholas Sant
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.,University of Vermont, Burlington, Vermont, USA.,Members of the BEAR Trial Team are listed in the Authors section at the end of this article.,Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Braden C Fleming
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.,University of Vermont, Burlington, Vermont, USA.,Members of the BEAR Trial Team are listed in the Authors section at the end of this article.,Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Lyle J Micheli
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts, USA.,University of Vermont, Burlington, Vermont, USA.,Members of the BEAR Trial Team are listed in the Authors section at the end of this article.,Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
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Sant NJ, Proffen BL, Murray MM. Effects of radiation dose and nitrogen purge on collagen scaffold properties. J Biomater Appl 2021; 36:1011-1018. [PMID: 34607497 DOI: 10.1177/08853282211047683] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Sterilization of medical devices is commonly performed using radiation methods. However, collagen materials can be damaged when using standard radiation doses (25 kGy). Small increases of radiation dose can allow for increases in the acceptable initial bioburden load of aseptically manufactured devices while maintaining required sterility assurance levels, which is often critical in early stage translational settings. In this study, we hypothesized that small increases in radiation dose from 15 to 20 kGy would result in significant changes to several key characteristics of collagen scaffolds. Scaffolds were manufactured by lyophilizing the pepsin digest of dense bovine connective tissue in cylindrical molds and were irradiated at either 0, 15, 17.5, or 20 kGy with an additional group packaged in nitrogen and irradiated at 17.5 kGy. Groups were evaluated for changes to the soluble collagen and glycosaminoglycan mass fractions, protein banding patterns in electrophoresis, a collagen fragmentation assay, and resistance to enzymatic degradation. All parameters were statistically analyzed using one-way analysis of variance with Tukey's correction for multiple comparisons. The soluble collagen mass fraction was significantly decreased in the 20 kGy group; however, there was no significant effect of radiation dose or a nitrogen-rich environment on the other measured parameters, including protein banding patterns, fragmented collagen content, and resistance to enzymatic degradation.Statement of Clinical Significance: Collagen scaffolds have proven useful in clinical applications but can be damaged by standard radiation doses. Low-dose sterilization may be a viable alternative that minimally impacts key properties of these scaffolds.
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Affiliation(s)
- Nicholas J Sant
- Department of Orthopaedic Surgery, 1862Boston Children's Hospital, Boston, MA, USA
| | - Benedikt L Proffen
- Department of Orthopaedic Surgery, 1862Boston Children's Hospital, Boston, MA, USA
| | - Martha M Murray
- Department of Orthopaedic Surgery, 1862Boston Children's Hospital, Boston, MA, USA
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10
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Szwedowski D, Paczesny Ł, Zabrzyński J, Gagat M, Domżalski M, Huri G, Widuchowski W. The Comparison of Clinical Result between Primary Repair of the Anterior Cruciate Ligament with Additional Internal Bracing and Anatomic Single Bundle Reconstruction-A Retrospective Study. J Clin Med 2021; 10:jcm10173948. [PMID: 34501400 PMCID: PMC8432121 DOI: 10.3390/jcm10173948] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 06/30/2021] [Accepted: 08/23/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The current standard of treatment of anterior cruciate ligament (ACL) is reconstruction (ACLR). This technique has some disadvantages: poor proprioception, donor site morbidity and the inability to restore joint kinematics. ACL repair could be an alternative treatment. The purpose of the study was to compare the stability and the function after ACL primary repair versus single-bundle ACLR. METHODS In a retrospective study, 12 patients underwent primary ACL repair with internal bracing, 15 patients underwent standard ACLR. Follow-up examinations were evaluated at up to 2 years postoperatively. One patient in the ACL repair group was lost to follow-up due to re-rupture. The absolute value of anterior tibial translation (ATT) and the side-to-side difference in the same patient (ΔATT) were evaluated using the GNRB arthrometer. The Lysholm knee scoring was obtained. Re-ruptures and other complications were recorded. RESULTS Anterior tibial translation (ATT) was significantly decreased in the ACL repair group compared with the ACLR group (5.31 mm vs. 7.18 mm, respectively; p = 0.0137). Arthrometric measurements demonstrated a mean side-to-side difference (ΔATT) 1.87 (range 0.2 to 4.9) mm significantly decreased compared to ACLR 3.36 (range 1.2-5.6 mm; p = 0.0107). The mean Lysholm score was 85.3 points in the ACL repair group and 89.9 in ACLR group. No significant differences between ACL repair and ACLR were found for the Lysholm score. There was no association between AP laxity and clinical outcomes. There were two complications in the internal bracing group: one patient had re-rupture and was treated by ACLR, another had limited extension and had arthroscopic debridement. CONCLUSIONS Anterior tibial translation was significantly decreased after ACL repair. Additionally, the functional results after ACL repair with internal bracing were comparable with those after ACLR. It should be noted that the two complications occurred. The current study supports further development of ACL repair techniques.
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Affiliation(s)
- Dawid Szwedowski
- Orthopaedic Arthroscopic Surgery International (OASI) Bioresearch Foundation, 20133 Milan, Italy
- Correspondence:
| | - Łukasz Paczesny
- Citomed Healthcare Center, Department of Orthopaedics, Orvit Clinic, Sklodowskiej 73, 87-100 Toruń, Poland; (Ł.P.); (J.Z.)
| | - Jan Zabrzyński
- Citomed Healthcare Center, Department of Orthopaedics, Orvit Clinic, Sklodowskiej 73, 87-100 Toruń, Poland; (Ł.P.); (J.Z.)
- Department of General Orthopedics, Musculoskeletal Oncology and Trauma Surgery, University of Medical Sciences, 61-701 Poznan, Poland
| | - Maciej Gagat
- Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-067 Bydgoszcz, Poland;
| | - Marcin Domżalski
- Department of Orthopedic and Traumatology, Veterans Memorial Hospital, Medical University of Lodz, 90-549 Lodz, Poland;
| | - Gazi Huri
- Orthopaedics and Traumatology Department, Hacettepe Universitesi, Ankara 06100, Turkey;
| | - Wojciech Widuchowski
- Department of the Knee Surgery, Arthroscopy and Sports Traumatology, District Hospital of Orthopedics and Trauma Surgery, 41-940 Piekary Slaskie, Poland;
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Kobayashi EF, Tang K, Grant JA. Is ACL Repair Really Back? A Review of Modern Techniques. OPER TECHN SPORT MED 2021. [DOI: 10.1016/j.otsm.2021.150828] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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Burton DA, Schaefer EJ, Shu HT, Bodendorfer BM, Argintar EH. Primary Anterior Cruciate Ligament Repair Using Suture Tape Augmentation: A Case Series of 29 Patients With Minimum 2-Year Follow-Up. Arthroscopy 2021; 37:1235-1241. [PMID: 33581301 DOI: 10.1016/j.arthro.2020.11.034] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 02/02/2023]
Abstract
PURPOSE To evaluate clinical outcomes and patient-reported outcomes of patients who underwent primary anterior cruciate ligament (ACL) repair using suture tape augmentation. METHODS Patients with a proximal tear of the ACL who underwent primary ACL repair with a minimum 2-year follow-up were included. The exclusion criteria included multiligamentous knee injuries, midsubstance tears, tibial avulsion fractures, and distal tears. Demographic characteristics, injury pattern, concomitant injury pattern, and patient-reported outcome measures were recorded. Patients were evaluated at a minimum 2-year follow-up for clinical success, defined as stability not requiring revision ACL reconstruction, and for patient-reported outcome measurements. Failure was defined as the need for revision surgery. RESULTS The mean follow-up period was 2.8 ± 0.9 years. Thirty-five patients met the inclusion criteria, with an average age of 32.2 ± 7.2 years, and 2-year follow-up was obtained for 29 of these patients. Revision surgery was required in 2 of the 29 patients (6.9%); successful treatment was achieved in the remaining 93.1%. The Single Assessment Numeric Evaluation score and Knee Injury and Osteoarthritis Outcome Score for the 27 successfully treated patients were recorded, with 70.4% having Single Assessment Numeric Evaluation scores of 80 or greater. CONCLUSIONS This case series shows that primary surgical repair of proximal ACL tears using suture tape augmentation results in a low rate of revision surgery. LEVEL OF EVIDENCE Level IV, prospective case series.
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Affiliation(s)
- Denver A Burton
- Department of Orthopaedic Surgery, Georgetown University Medical Center, Washington, DC, U.S.A..
| | | | - Henry T Shu
- Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A
| | - Blake M Bodendorfer
- Department of Orthopaedic Surgery, Georgetown University Medical Center, Washington, DC, U.S.A
| | - Evan H Argintar
- Department of Orthopaedic Surgery, MedStarWashington Hospital Center, Washington, DC, U.S.A
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13
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Daggett MC, Busch K, Ferretti A, Monaco E, Bruni G, Saithna A. Percutaneous Anterior Cruciate Ligament Repair With Needle Arthroscopy and Biological Augmentation. Arthrosc Tech 2021; 10:e289-e295. [PMID: 33680758 PMCID: PMC7917016 DOI: 10.1016/j.eats.2020.10.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 10/08/2020] [Indexed: 02/03/2023] Open
Abstract
Recent advancements in orthopaedic devices have instilled a renewed interest in repair of the anterior cruciate ligament. Biological augmentation of the repair has also recently been investigated with the hopes of improving repair outcomes and improving biological healing. The advent of needle arthroscopy allows for potentially decreased recovery times and potentially reduced complication rates compared with traditional arthroscopy. The purpose of this article is to present a percutaneous technique to repair the anterior cruciate ligament with suture tape augmentation while also augmenting with the biological byproducts from the native effusion using needle arthroscopy.
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Affiliation(s)
- Matthew C. Daggett
- Address correspondence to Matthew C. Daggett, D.O., M.B.A., 2000 SE Blue Pkwy, Ste 230, Lee's Summit, MO 64063, U.S.A.
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Li Y, Fu SC, Cheuk YC, Ong TY, Feng H, Yung SH. The effect of thermosensitive hydrogel platelet-rich-plasma complex in the treatment of partial tear of anterior cruciate ligament in rat model. J Orthop Translat 2020; 24:183-189. [PMID: 33101969 PMCID: PMC7548349 DOI: 10.1016/j.jot.2019.12.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 12/19/2019] [Accepted: 12/22/2019] [Indexed: 01/13/2023] Open
Abstract
Background/Objective The treatment of anterior cruciate ligament (ACL) partial tear is controversial. The reconstructive surgery is invasive while the prevalence of subsequent insufficiency after conservative treatment has been reported to range from 11% to 62%. Therefore, a new method that promotes tissue regeneration is needed. The aim of this study was to observe the healing of ACL partial tear biomechanically and histologically after the administration of a thermosensitive hydrogel platelet-rich-plasma (PRP) complex. Methods The complex was prepared according to a previously published protocol. One hundred and fifty 12-week-old male Sprague-Dawley rats were included and they were allocated into 4 groups. Lesion control group (Group 1), treatment group (Group 2), gel-only group (Group 3) and intact group (Group 4). Biomechanical testing, histological analysis (H&E and immunohistochemical staining) and scoring was performed. Results On gross observation, the treatment group showed a continuous ACL with slightly thickened synovium or a partially healed ACL at 6-week follow up. In the biomechanical testing at 6 weeks after surgery, the failure load of the treatment group was significantly superior when compared with the lesion control group (52.7±10.8N vs. 41.6±7.8N, p<0.01), but the failure load was not restored to level of the intact group (52.7±10.8N vs. 61.5±9.1N, p=0.037). The maturity index of wound sites showed no significant inter-group differences at any timepoints. However, an increased expression of vascular endothelial growth factor (VEGF) and pro-collagen I was detected. Conclusion The thermosensitive hydrogel-PRP was shown to be effective in enhancing the healing of ACL partial tear in the rat model, and potentially this complex can be used as a treatment for patients with ACL partial tear. The translational potential of this article The thermosensitive hydrogel-PRP is potentially translated to clinical use to treat patients with ACL partial tear by injection under arthroscopy or ultrasound guiding.
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Affiliation(s)
- Yue Li
- Sports Medicine Service, Beijing Jishuitan Hospital, Beijing, China
| | - Sai C Fu
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yau C Cheuk
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Tim-Yun Ong
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Hua Feng
- Sports Medicine Service, Beijing Jishuitan Hospital, Beijing, China
| | - Shu-Hang Yung
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
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15
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Barnett S, Murray MM, Liu S, Micheli LJ. Resolution of Pain and Predictors of Postoperative Opioid use after Bridge-Enhanced Anterior Cruciate Ligament Repair and Anterior Cruciate Ligament Reconstruction. Arthrosc Sports Med Rehabil 2020; 2:e219-e228. [PMID: 32548587 PMCID: PMC7283945 DOI: 10.1016/j.asmr.2020.02.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 02/12/2020] [Indexed: 01/08/2023] Open
Abstract
Purpose To compare postoperative pain scores and opioid use between patients undergoing a standard arthroscopic anterior cruciate ligament reconstruction (ACLR) using hamstring autograft with those undergoing a suture repair augmented with an extracellular matrix scaffold (bridge-enhanced ACL repair) performed through an arthrotomy and to determine factors predictive of postoperative opioid use and levels of overprescription. Methods A nonrandomized controlled trial was conducted with 20 patients (10 ACLR, 10 bridge-enhanced ACL repair), aged 18 to 35 years. All surgeries were performed by a single surgeon. A pain medication log was provided to patients on discharge. No regional anesthesia was performed. Pain scores via a visual analog pain scale were recorded at each visit. Correlations between preoperative and intraoperative characteristics and postoperative opioid use were determined. Results The total morphine-equivalent dose ranged from 30 to 309 mg (4-42 pills oxycodone) for the ACLR group and 75 to 254 mg (10-34 pills oxycodone) for the bridge-enhanced ACL repair group. The average opioid use per day was 35.8 mg for the patients undergoing bridge-enhanced ACL repair and 44.2 mg for patients undergoing ACLR (P = .29). Pain scores at time points up to 2 years postoperatively were not significantly different between the 2 groups. Across both groups, the average oversupply of oxycodone was 46 pills per patient, a greater than 70% unused opiate rate. Preoperative body mass index and preoperative Knee Injury and Osteoarthritis Outcome Scores pain score were predictive of greater postoperative opioid use per day, whereas age, concurrent meniscal repair, and operative time were not. Conclusions Total overall opiate intake was not different between the patients undergoing bridge-enhanced ACL repair through an arthrotomy and those undergoing arthroscopic ACLR. Both groups had similar pain scores from 2 weeks to 2 years postoperatively. Greater body mass index and greater preoperative pain (lower Knee Injury and Osteoarthritis Outcome Scores pain score) correlated with greater postoperative opioid use per day. There was an overprescription of opioids across all patients. Level of Evidence Level III, case control study (therapeutic).
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Affiliation(s)
- Samuel Barnett
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, U.S.A
| | - Martha M Murray
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, U.S.A
| | - Shanshan Liu
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital Boston, Massachusetts, U.S.A
| | | | - Lyle J Micheli
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, U.S.A
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Murray MM, Fleming BC, Badger GJ, The BEAR Trial Team, Freiberger C, Henderson R, Barnett S, Kiapour A, Ecklund K, Proffen B, Sant N, Kramer DE, Micheli LJ, Yen YM. Bridge-Enhanced Anterior Cruciate Ligament Repair Is Not Inferior to Autograft Anterior Cruciate Ligament Reconstruction at 2 Years: Results of a Prospective Randomized Clinical Trial. Am J Sports Med 2020; 48:1305-1315. [PMID: 32298131 PMCID: PMC7227128 DOI: 10.1177/0363546520913532] [Citation(s) in RCA: 135] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Preclinical studies suggest that for complete midsubstance anterior cruciate ligament (ACL) injuries, a suture repair of the ACL augmented with a protein implant placed in the gap between the torn ends (bridge-enhanced ACL repair [BEAR]) may be a viable alternative to ACL reconstruction (ACLR). HYPOTHESIS We hypothesized that patients treated with BEAR would have a noninferior patient-reported outcomes (International Knee Documentation Committee [IKDC] Subjective Score; prespecified noninferiority margin, -11.5 points) and instrumented anteroposterior (AP) knee laxity (prespecified noninferiority margin, +2-mm side-to-side difference) and superior muscle strength at 2 years after surgery when compared with patients who underwent ACLR with autograft. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS One hundred patients (median age, 17 years; median preoperative Marx activity score, 16) with complete midsubstance ACL injuries were enrolled and underwent surgery within 45 days of injury. Patients were randomly assigned to receive either BEAR (n = 65) or autograft ACLR (n = 35 [33 with quadrupled semitendinosus-gracilis and 2 with bone-patellar tendon-bone]). Outcomes-including the IKDC Subjective Score, the side-to-side difference in instrumented AP knee laxity, and muscle strength-were assessed at 2 years by an independent examiner blinded to the procedure. Patients were unblinded after their 2-year visit. RESULTS In total, 96% of the patients returned for 2-year follow-up. Noninferiority criteria were met for both the IKDC Subjective Score (BEAR, 88.9 points; ACLR, 84.8 points; mean difference, 4.1 points [95% CI, -1.5 to 9.7]) and the side-to-side difference in AP knee laxity (BEAR, 1.61 mm; ACLR, 1.77 mm; mean difference, -0.15 mm [95% CI, -1.48 to 1.17]). The BEAR group had a significantly higher mean hamstring muscle strength index than the ACLR group at 2 years (98.2% vs 63.2%; P < .001). In addition, 14% of the BEAR group and 6% of the ACLR group had a reinjury that required a second ipsilateral ACL surgical procedure (P = .32). Furthermore, the 8 patients who converted from BEAR to ACLR in the study period and returned for the 2-year postoperative visit had similar primary outcomes to patients who had a single ipsilateral ACL procedure. CONCLUSION BEAR resulted in noninferior patient-reported outcomes and AP knee laxity and superior hamstring muscle strength when compared with autograft ACLR at 2-year follow-up in a young and active cohort. These promising results suggest that longer-term studies of this technique are justified. REGISTRATION NCT02664545 (ClinicalTrials.gov identifier).
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Affiliation(s)
- Martha M. Murray
- Martha M. Murray, MD, Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children’s Hospital, 300 Longwood Ave, Hunnewell 2, Boston, MA 02115, USA ()
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Chahla J, Nelson T, Dallo I, Yalamanchili D, Eberlein S, Limpisvasti O, Mandelbaum B, Metzger MF. Anterior cruciate ligament repair versus reconstruction: A kinematic analysis. Knee 2020; 27:334-340. [PMID: 31813701 DOI: 10.1016/j.knee.2019.10.020] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 10/10/2019] [Accepted: 10/24/2019] [Indexed: 02/02/2023]
Abstract
BACKGROUND The purpose of this study was to compare the biomechanical properties of an anterior cruciate ligament (ACL) anatomic repair of a true femoral avulsion to an anatomic ACL reconstruction. It was hypothesized that the ACL repair and ACL reconstruction would have comparable biomechanical behavior when compared to the native knee. METHODS Ten paired fresh-frozen cadaveric knees (n = 20) were used to investigate knee kinematics when an anterior drawer force, varus, valgus, internal, and external rotational moment were applied at 0, 15, 30, 45, 60, and 90 degrees of flexion. Displacement and rotation were recorded in the following conditions: ACL-intact, ACL-deficient, and ACL-repaired vs reconstructed. RESULTS Sectioning of the ACL significantly increased anterior tibial translation (0°, 15°, 30° and 45°) compared to the intact state. The mean anterior displacement difference from intact was lower in the ACL-repaired knees compared to reconstructed knees at 30° and 90°. There were no significant differences between conditions in varus, valgus, internal, or external rotations. CONCLUSION ACL repair and ACL reconstruction procedures restored knee anterior tibial translation in matched paired specimens. There were no differences in valgus, varus, internal, or external rotation. Although, ACL-repaired knees (avulsion model) demonstrated less anterior tibial translation when compared to ACL-reconstructed knees, this difference was less than one millimeter. Based on the findings of this study, repair and reconstruction procedures both restored anterior tibial translation in matched-pair specimens. This suggests that the initial functionality of both techniques is similar and that further clinical studies are needed to compare the long-term stability.
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Affiliation(s)
- Jorge Chahla
- Cedars-Sinai Kerlan-Jobe Institute, Santa Monica, CA, United States of America
| | - Trevor Nelson
- Orthopaedic Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
| | - Ignacio Dallo
- Unit of Regenerative Therapy and Arthroscopy Surgery, Sanatorio Garay, Santa Fe, Argentina
| | - Dheeraj Yalamanchili
- Department of Orthopaedic Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.
| | - Sam Eberlein
- Orthopaedic Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
| | - Orr Limpisvasti
- Cedars-Sinai Kerlan-Jobe Institute, Santa Monica, CA, United States of America
| | - Bert Mandelbaum
- Cedars-Sinai Kerlan-Jobe Institute, Santa Monica, CA, United States of America
| | - Melodie F Metzger
- Orthopaedic Biomechanics Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America
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Hoogeslag RAG, Brouwer RW, Huis In 't Veld R, Amis AA. Isometric placement of the augmentation braid is not attained reliably in contemporary ACL suture repair. Knee 2020; 27:111-123. [PMID: 31791721 DOI: 10.1016/j.knee.2019.10.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 10/18/2019] [Accepted: 10/20/2019] [Indexed: 02/02/2023]
Abstract
BACKGROUND To assess if during arthroscopic braid-augmented ACL suture repair (ACLSR), the actual positions of the augmentation braids' tunnels corresponded with the positions of their intended and targeted isometric points, and to test the hypothesis that there would be no dispersion in actual positions of the augmentation braids' tunnels compared to their intended and targeted isometric points. METHODS In 12 human cadaveric knees, the positions of the augmentation braids' tunnels and their intended and targeted isometric points relative to a femoral and tibial grid were analysed. Furthermore, vector length between these positions was calculated to assess the accuracy and precision of the augmentation braids' tunnel placement. RESULTS There was dispersion for all of the augmentation braids' tunnel positions compared to their intended isometric points. The femoral and tibial vector lengths (mean ± SD (range)) were 2.9 ± 1.0 (1.1-4.1) and 7.1 ± 2.0 (3.2-9.8) mm respectively. CONCLUSION In augmented ACLSR, with the ruptured ACL in situ, there was dispersion of the positions of the actual small diameter femoral and tibial augmentation braids' tunnels away from their desired isometric points. CLINICAL RELEVANCE The extent of dispersion of the position of both the femoral and tibial tunnels away from their intended isometric positions may cause cyclic length changes with knee motion. An ACLSR with static braid augmentation will thus be vulnerable to cyclic stretching-out. The difficulty of obtaining an isometric tunnel combination for the small diameter augmentation braid may influence the clinician's choice between non-, static or dynamic augmented ACLSR techniques.
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Affiliation(s)
- Roy A G Hoogeslag
- Department of Mechanical Engineering, Imperial College London, London SW7 2AZ, UK.
| | - Reinoud W Brouwer
- Department of Mechanical Engineering, Imperial College London, London SW7 2AZ, UK.
| | | | - Andrew A Amis
- Department of Mechanical Engineering, Imperial College London, London SW7 2AZ, UK; Musculoskeletal Surgery Group, Imperial College London School of Medicine, Charing Cross Hospital, London W6 8RF, UK.
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Wang H, Kang H, Yao J, Cheng CK, Woo SLY. Evaluation of a magnesium ring device for mechanical augmentation of a ruptured ACL: Finite element analysis. Clin Biomech (Bristol, Avon) 2019; 68:122-127. [PMID: 31200296 DOI: 10.1016/j.clinbiomech.2019.06.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Revised: 05/04/2019] [Accepted: 06/04/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Recently, a ring device was used for mechanical augmentation to aid the healing of ACL. In-vivo study using goat showed improved joint stability after ring repair in comparison to using biological augmentation alone. Objective of this study was to quantify the load and stress levels in the ACL and its femoral insertion site following ring repair. METHODS A three dimensional finite element model of a goat stifle joint was developed to find the load and stress level in the ACL and at its femoral insertion site following ring repair. FINDINGS Ring repair led to approximately a 50% reduction in anterior-posterior tibial translation over the model with a deficient ACL: 5.2 mm vs 10.6 mm, 4.4 mm vs 9.0 mm, and 2.9 mm vs 5.2 mm at joint flexion angles of 37°, 60° and 90° respectively. After ring repair, the in situ force in the ACL was restored to be nearly 60% of the intact ACL. The maximum Von Mises stress at the femoral insertion site was up to 71% of those for the intact ACL. INTERPRETATION This study offers new knowledge on the function of a ring device to mechanically augment ACL repair in order to improve its healing. Quantitative data on loading levels in the repaired ACL and its insertion site that led to its healing could be used as basis for developing novel devices to mechanically augment the healing of ACL in humans.
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Affiliation(s)
- Huizhi Wang
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China; Musculoskeletal Research Center, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Huijun Kang
- Musculoskeletal Research Center, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Jie Yao
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China
| | - Cheng-Kung Cheng
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China; Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100191, China.
| | - Savio L-Y Woo
- Musculoskeletal Research Center, University of Pittsburgh, Pittsburgh, PA 15219, USA.
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Murray MM, Kalish LA, Fleming BC, Flutie B, Freiberger C, Henderson RN, Perrone GS, Thurber LG, Proffen BL, Ecklund K, Kramer DE, Yen YM, Micheli LJ. Bridge-Enhanced Anterior Cruciate Ligament Repair: Two-Year Results of a First-in-Human Study. Orthop J Sports Med 2019; 7:2325967118824356. [PMID: 30923725 PMCID: PMC6431773 DOI: 10.1177/2325967118824356] [Citation(s) in RCA: 107] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
Background Bridge-enhanced anterior cruciate ligament repair (BEAR) combines suture repair of the anterior cruciate ligament (ACL) with a specific extracellular matrix scaffold (the BEAR scaffold) that is placed in the gap between the torn ends of the ACL to facilitate ligament healing. Purpose/Hypothesis The purpose of this study was to report the 12- and 24-month outcomes of patients who underwent the BEAR procedure compared with a nonrandomized concurrent control group who underwent ACL reconstruction (ACLR) with an autograft. We hypothesized that the BEAR group would have physical examination findings, patient-reported outcomes, and adverse events that were similar to those of the ACLR group. Study Design Cohort study; Level of evidence, 2. Methods Ten patients underwent BEAR, and 10 underwent ACLR with a 4-stranded hamstring autograft. At 24 months, 9 of the 10 BEAR patients and 7 of the 10 ACLR patients completed a study visit. Outcomes reported included International Knee Documentation Committee (IKDC) subjective and objective results, knee anteroposterior (AP) laxity findings via an arthrometer, and functional outcomes. Results There were no graft or repair failures in the first 24 months after surgery. The IKDC subjective scores in both groups improved significantly from baseline (P < .0001) at 12 and 24 months, to 84.6 ± 17.2 in the ACLR group and to 91.7 ± 11.7 in the BEAR group. An IKDC objective grade of A (normal) was found in 44% of patients in the BEAR group and in 29% of patients in the ACLR group at 24 months; no patients in either group had C (abnormal) or D (severely abnormal) grades. Arthrometer testing demonstrated mean side-to-side differences in AP laxity that were similar in the 2 groups at 24 months (BEAR, 1.94 ± 2.08 mm; ACLR, 3.14 ± 2.66 mm). Functional hop testing results were similar in the 2 groups at 12 and 24 months after surgery. Hamstring strength indices were significantly higher in the BEAR group compared with the ACLR group (P = .0001). Conclusion In this small, first-in-human study, BEAR produced similar outcomes to ACLR with a hamstring autograft. BEAR may result in knee stability and patient-reported outcomes at 2 years sufficient to warrant longer term studies of efficacy in larger groups of patients.
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Affiliation(s)
- Martha M Murray
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Leslie A Kalish
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Braden C Fleming
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | | | - Brett Flutie
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Christina Freiberger
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Rachael N Henderson
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Gabriel S Perrone
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Laura G Thurber
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Benedikt L Proffen
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Kirsten Ecklund
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Dennis E Kramer
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Yi-Meng Yen
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
| | - Lyle J Micheli
- Investigation performed at Boston Children's Hospital, Boston, Massachusetts, USA
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Arthroscopic primary repair of proximal anterior cruciate ligament tears: outcomes of the first 56 consecutive patients and the role of additional internal bracing. Knee Surg Sports Traumatol Arthrosc 2019; 27:21-28. [PMID: 30612165 DOI: 10.1007/s00167-018-5338-z] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 12/07/2018] [Indexed: 02/06/2023]
Abstract
PURPOSE Recent outcomes of arthroscopic primary repair of proximal anterior cruciate ligament (ACL) tears have been promising in small cohort studies. The purpose of this study was to assess outcomes of arthroscopic ACL repair in a larger cohort and to assess the role of additional augmentation. METHODS The first 56 consecutive patients that underwent arthroscopic ACL repair were examined at minimum 2-year follow-up. The latter 27 patients [48.2% (27/56)] received additional internal bracing with ACL repair. All 56 patients were included (100% follow-up). Mean age at surgery was 33.5 ± 11.3 years (59% male) and mean follow-up 3.2 ± 1.7 years. Clinical examination was performed using the objective International Knee Documentation Committee (IKDC) form. Subjective outcomes were obtained using the Lysholm, modified Cincinnati, Single Assessment Numeric Evaluation (SANE), and subjective IKDC scores. RESULTS Six repairs (10.7%) failed and four additional patients underwent reoperation (7.1%): two for meniscus tears and two for suture anchor irritation. Objective IKDC scores were A in 38 (73%), B in 8 (15%) and C/D in 6 (12%) patients. Mean Lysholm score was 94 ± 7.6, modified Cincinnati 94 ± 8.9, SANE 90 ± 12.5, pre-injury Tegner 6.7 ± 1.5, current Tegner 6.2 ± 1.5, and subjective IKDC 90 ± 10.9. Failures rates were 7.4% with and 13.8% without internal bracing (P = 0.672). There were no statistically significant or clinically relevant differences in subjective outcomes. CONCLUSION Arthroscopic primary repair has resulted in good objective and subjective outcomes at 3.2-year follow-up in a carefully selected population. The role of additional internal bracing is possibly beneficial, but larger groups are needed to assess this. LEVEL OF EVIDENCE III.
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Pauvert A, Robert H, Gicquel P, Graveleau N, Pujol N, Chotel F, Lefevre N. MRI study of the ligamentization of ACL grafts in children with open growth plates. Orthop Traumatol Surg Res 2018; 104:S161-S167. [PMID: 30314939 DOI: 10.1016/j.otsr.2018.09.003] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 09/06/2018] [Indexed: 02/02/2023]
Abstract
INTRODUCTION There is little published information on the ligamentization of pediatric anterior cruciate ligament (ACL) grafts. The aims of our study were to compare the MRI appearance of ACL grafts performed in a population with open growth plates to normal ACLs in adolescents and to determine whether the MRI signal in the grafts at 6 months could predict a retear. We hypothesized that ligamentization was a slow, gradual process. MATERIAL AND METHODS This was a prospective multicenter study of 100 ACL grafts (quadriceps tendon, hamstring tendon, fascia lata) in children 7 to 16 years of age. Of these, 65 intact grafts underwent one or more MRI examinations between 6 months and 2 years postoperative. MRI images were also analyzed in 7 patients who suffered a retear and in the intact ACL of 20 adolescents (15 to 18 years of age). The other 28 patients did not undergo an MRI during the postoperative phase. For each MRI, the signal-to-noise quotient (SNQ) was calculated in three different areas in the ACL (proximal, middle, distal) along with the Howell intra-articular and intra-tibial grades from I to IV. The Mantel-Haenszel Chi-square, Wilcoxon signed-rank test and Student's t-test were used to compare groups. The Lin concordance correlation coefficients were calculated for inter-rater consistency. RESULTS There was a difference in the SNQ between the three zones of a normal ACL. Most were Howell grade III (55% Howell III, 25% Howell II and 20% Howell I). For intact grafts, the SNQ improved significantly between 6 and 12 months and between 6 and 24 months. There was no difference in the SNQ between the three zones independent of the postoperative time point. The intra-articular Howell grade improved significantly between 6 and 24 months and between 12 and 24 months. The intra-tibial Howell grade improved significantly between 12 and 24 months. There were no significant differences between patients with intact grafts and those who suffered a retear. There were no differences between the various types of grafts used. CONCLUSION Normal ACLs in adolescents have inhomogeneous SNQ and Howell grades. The SNQ and Howell grades in ACL grafts are more homogeneous and continue to improve out to 2 years, but do not reach that of a normal ACL. The signal and appearance of an ACL graft and normal ACL are very different, and the MRI signal at 6 months postoperative is not predictive of retear. LEVEL OF EVIDENCE III, prospective study.
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Affiliation(s)
- Adrien Pauvert
- Department of Orthopaedic Surgery, Centre hospitalier Nord Mayenne, 229 boulevard Paul-Lintier, 53100 Mayenne, France.
| | - Henri Robert
- Department of Orthopaedic Surgery, Centre hospitalier Nord Mayenne, 229 boulevard Paul-Lintier, 53100 Mayenne, France
| | - Philippe Gicquel
- Pediatric orthopedics department, Strasbourg university hospital center, Hautepierre hospital, avevue Molière, 67098 Strasbourg, France
| | - Nicolas Graveleau
- CCOS & Sport clinic of Bordeaux-Mérignac, 2, avenue Georges-de-Negrevergne, 33700 Mérignac, France
| | - Nicolas Pujol
- Department Orthopaedic Surgery, Centre Hospitalier de Versailles, 177, rue de Versailles, 78150 Le Chesnay, France
| | - Franck Chotel
- Pediatric orthopedics department, Hôpital Femme Mere Enfant, 59, boulevard Pinel, 69677, Lyon, France
| | - Nicolas Lefevre
- Department Orthopaedic Sport Surgery, Clinique du sport, Groupe Ramsay-Générale de Santé, 36 boulevard St Marcel, 75005 Paris, France; Orthopaedic Institut, Clinique Nollet, 23, rue Brochant, 75017 Paris, France
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- 15 rue Ampère, 92500 Rueil Malmaison, France
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23
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Christensen K, Cox B, Anz A. Emerging Orthobiologic Techniques and the Future. Clin Sports Med 2018; 38:143-161. [PMID: 30466719 DOI: 10.1016/j.csm.2018.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The future of orthopedic surgery appears to be intimately associated with the development of orthobiologics to facilitate healing and the treatment of multiple disease processes. The orthopedic community should understand developmental processes to ensure that products are adequately studied and the effects are fully known before widespread implementation in the clinical setting. Technologies that embrace this paradigm will impact the field the most.
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Affiliation(s)
- Kevin Christensen
- Andrews Institute, 1040 Gulf Breeze Parkway, Gulf Breeze, FL 32561, USA
| | - Benjamin Cox
- PLLC, 2890 Health Parkway, Mount Pleasant, MI 48858, USA
| | - Adam Anz
- Andrews Institute, Andrews Research and Education Foundation, 1040 Gulf Breeze Parkway, Gulf Breeze, FL 32561, USA.
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24
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Li Y, Fu SC, Cheuk YC, Song G, Feng H, Yung SH. The non-reconstructive treatment of complete ACL tear with biological enhancement in clinical and preclinical studies: A systematic review. Asia Pac J Sports Med Arthrosc Rehabil Technol 2018; 14:10-16. [PMID: 30302314 PMCID: PMC6170796 DOI: 10.1016/j.asmart.2018.04.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 03/28/2018] [Accepted: 04/09/2018] [Indexed: 01/15/2023] Open
Abstract
Introduction There is still controversy regarding the bio-enhanced non-reconstructive ACL treatment. Materials and methods A search for articles in databases was performed in February 2017. The objective and subjective evaluations of clinical studies and biomechanical and histological data of preclinical studies were extracted. Results Eighteen articles were included for analysis. In clinical studies, although subjective scores were significantly improved, the rate of re-operation rate was high. In preclinical studies, bio-enhancing techniques demonstrated promotion of the healing of ACL. Conclusions The efficacy of biological enhancement cannot be validated in clinical studies. Preclinical studies showed improved biomechanical and healing potential.
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Affiliation(s)
- Yue Li
- Sports Medicine Service, Beijing Jishuitan Hospital, China
| | - Sai Cheun Fu
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yau Chuk Cheuk
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Guanyang Song
- Sports Medicine Service, Beijing Jishuitan Hospital, China
| | - Hua Feng
- Sports Medicine Service, Beijing Jishuitan Hospital, China
| | - Shu-Hang Yung
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, China.,Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Hong Kong, China
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25
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Gil JA, Chambers A, Shah KN, Crisco JJ, Got C, Akelman E. A Biomechanical Evaluation of a 2-Suture Anchor Repair Technique for Thumb Metacarpophalangeal Joint Ulnar Collateral Ligament Injuries. Hand (N Y) 2018; 13:581-585. [PMID: 28836462 PMCID: PMC6109898 DOI: 10.1177/1558944717725380] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND A complete thumb ulnar collateral ligament (UCL) repaired with 1-suture anchor has been demonstrated to be significantly weaker compared with the intact UCL. The objective of this study is to test the biomechanical strength of a 2-anchor thumb UCL repair. METHODS Nine paired fresh-frozen hands were used for this biomechanical analysis. One thumb from each pair was randomized to the control group and one to the repair group. In the control group, the UCL was loaded to failure in tension. In the repair group, the UCL was dissected off of the proximal phalanx, subsequently repaired with a 2-anchor technique, and then tested to failure. RESULTS The mean yield load was 342 N (95% confidence interval [CI], 215-470 N) in the control group and 68 N (95% CI, 45-91 N) in the repair group. The mean maximum load at failure was 379 N (95% CI, 246-513 N) in the control group and 84 N (95% CI, 62-105 N) in the repair group. The mean stiffness was 72 N/m (95% CI, 48-96 N/m) in the control group and 17 N/m (95% CI, 13-21 N) in the repair group. The mean displacement at failure was 7.8 mm (95% CI, 7-9 mm) in the control group and 7.8 mm (95% CI, 7-9 mm) in the repair group. CONCLUSIONS The 2-anchor repair technique we tested does not acutely reestablish the strength of the insertion of the native insertion of the UCL with this technique.
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Affiliation(s)
- Joseph A. Gil
- Brown University, Providence, RI, USA,Joseph A. Gil, Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, 593 Eddy Street, Providence, RI 02903, USA.
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26
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van Eck CF, Limpisvasti O, ElAttrache NS. Is There a Role for Internal Bracing and Repair of the Anterior Cruciate Ligament? A Systematic Literature Review. Am J Sports Med 2018; 46:2291-2298. [PMID: 28783472 DOI: 10.1177/0363546517717956] [Citation(s) in RCA: 99] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Renewed interest has arisen in arthroscopic anterior cruciate ligament (ACL) repair techniques. HYPOTHESIS ACL repair with or without some form of internal bracing could lead to good outcomes in a carefully selected subset of patients. STUDY DESIGN Systematic review. METHODS An electronic database search was performed to identify 89 papers describing preclinical and clinical studies on the outcome of ACL repair. RESULTS Proximal ACL tear patterns showed a better healing potential with primary repair than distal or midsubstance tears. Some form of internal bracing increased the success rate of ACL repair. Improvement in the biological characteristics of the repair was obtained by bone marrow access by drilling tunnels or microfracture. Augmentation with platelet-rich plasma was beneficial only in combination with a structural scaffold. Skeletally immature patients had the best outcomes. Acute repair offered improved outcomes with regard to load, stiffness, laxity, and rerupture. CONCLUSION ACL repair may be a viable option in young patients with acute, proximal ACL tears. The use of internal bracing, biological augmentation, and scaffold tissue may increase the success rate of repair.
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Affiliation(s)
| | - Orr Limpisvasti
- Kerlan Jobe Orthopaedic Clinic, Los Angeles, California, USA
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27
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Mahapatra P, Horriat S, Anand BS. Anterior cruciate ligament repair - past, present and future. J Exp Orthop 2018; 5:20. [PMID: 29904897 PMCID: PMC6002325 DOI: 10.1186/s40634-018-0136-6] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 05/31/2018] [Indexed: 12/14/2022] Open
Abstract
Background This article provides a detailed narrative review on the history and current concepts surrounding ligamentous repair techniques in athletic patients. In particular, we will focus on the anterior cruciate ligament (ACL) as a case study in ligament injury and ligamentous repair techniques. PubMed (MEDLINE), EMBASE and Cochrane Library databases for papers relating to primary anterior cruciate ligament reconstruction were searched by all participating authors. All relevant historical papers were included for analysis. Additional searches of the same databases were made for papers relating to biological enhancement of ligament healing. Current standard The poor capacity of the ACL to heal is one of the main reasons why the current gold standard surgical treatment for an ACL injury in an athletic patient is ACL reconstruction with autograft from either the hamstrings or patella tendon. It is hypothesised that by preserving and repairing native tissues and negating the need for autograft that primary ACL repair may represent a key step change in the treatment of ACL injuries. History of primary ACL repair The history of primary ACL repair will be discussed and the circumstances that led to the near-abandonment of primary ACL repair techniques will be reviewed. New primary repair techniques There has been a recent resurgence in interest with regards to primary ACL repair. Improvements in imaging now allow for identification of tear location, with femoral-sided injuries, being more suitable for repair. We will discuss in details strategies for improving the mechanical and biological environment in order to allow primary healing to occur. In particular, we will explain mechanical supplementation such as Internal Brace Ligament Augmentation and Dynamic Intraligamentary Stabilisation techniques. These are novel techniques that aim to protect the primary repair by providing a stabilising construct that connects the femur and the tibia, thus bridging the repair. Bio enhanced repair In addition, biological supplementation is being investigated as an adjunct and we will review the current literature with regards to bio-enhancement in the form platelet rich plasma, bio-scaffolds and stem cells. On the basis of current evidence, there appears to be a role for bio-enhancement, however, this is not yet translated into clinical practice. Conclusions Several promising avenues of further research now exist in the form of mechanical and biological augmentation techniques. Further work is clearly needed but there is renewed interest and focus for primary ACL repair that may yet prove the new frontier in ligament repair.
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Affiliation(s)
- Piyush Mahapatra
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK.
| | - Saman Horriat
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK
| | - Bobby S Anand
- Trauma and Orthopaedic Department, Croydon University Hospital, 530 London Road, London, CR7 7YE, UK
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28
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Beveridge JE, Machan JT, Walsh EG, Kiapour AM, Karamchedu NP, Chin KE, Proffen BL, Sieker JT, Murray MM, Fleming BC. Magnetic resonance measurements of tissue quantity and quality using T 2 * relaxometry predict temporal changes in the biomechanical properties of the healing ACL. J Orthop Res 2018; 36:1701-1709. [PMID: 29227559 PMCID: PMC5995620 DOI: 10.1002/jor.23830] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 12/04/2017] [Indexed: 02/04/2023]
Abstract
The purpose of this study was to develop a magnetic resonance T2 * relaxometry-based multiple linear regression model to predict the structural properties of the healing anterior cruciate ligament (ACL) over a 24-week healing period following ACL repair in Yucatan minipigs. Two hypotheses were tested: (i) that a regression model based on ACL sub-volumes containing short and long T2 * relaxation times would outperform a competing model based on sub-volumes of short T2 * relaxation times only; and (ii) that an optimized regression model would be capable of predicting ACL structural properties between 6 and 24 weeks post-repair. ACLs were imaged in 24 minipigs (8/group) at either 6, 12, or 24 weeks after ACL repair. The structural properties of the ACLs were determined from tensile failure tests. Four multiple linear regression models of increasing complexity were fitted to the data. Akaike Information Criterion values and Bland-Altman tests were used to compare model performance and to test the hypotheses. The structural properties predicted from the multiple linear regression model that was based on the change in ACL sub-volumes of both the short and long T2 * relaxation times over the healing period were in closest agreement to the measured values, suggesting that the amounts of both organized and disorganized collagen, and the change in these quantities over time, are required to predict the structural properties of healing ACLs accurately. CLINICAL SIGNIFICANCE our time-specific, T2 *-based regression model may allow us to estimate the structural properties of ACL repairs in vivo longitudinally. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1701-1709, 2018.
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Affiliation(s)
- Jillian E Beveridge
- Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Jason T Machan
- Rhode Island Hospital Biostatistics Core, Providence, Rhode Island
| | - Edward G Walsh
- Division of Biology and Medicine, Department of Neuroscience, Brown University, Providence, Rhode Island
| | | | - Naga Padmini Karamchedu
- Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | - Kaitlyn E Chin
- Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island
| | | | | | | | - Braden C Fleming
- Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island
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29
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Bez M, Kremen TJ, Tawackoli W, Avalos P, Sheyn D, Shapiro G, Giaconi JC, Ben David S, Snedeker JG, Gazit Z, Ferrara KW, Gazit D, Pelled G. Ultrasound-Mediated Gene Delivery Enhances Tendon Allograft Integration in Mini-Pig Ligament Reconstruction. Mol Ther 2018; 26:1746-1755. [PMID: 29784586 DOI: 10.1016/j.ymthe.2018.04.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Revised: 04/18/2018] [Accepted: 04/20/2018] [Indexed: 02/01/2023] Open
Abstract
Ligament injuries occur frequently, substantially hindering routine daily activities and sports participation in patients. Surgical reconstruction using autogenous or allogeneic tissues is the gold standard treatment for ligament injuries. Although surgeons routinely perform ligament reconstructions, the integrity of these reconstructions largely depends on adequate biological healing of the interface between the ligament graft and the bone. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would lead to significantly improved ligament graft integration. To test this hypothesis, an anterior cruciate ligament reconstruction procedure was performed in Yucatan mini-pigs. A collagen scaffold was implanted in the reconstruction sites to facilitate recruitment of endogenous mesenchymal stem cells. Ultrasound-mediated reporter gene delivery successfully transfected 40% of cells recruited to the reconstruction sites. When BMP-6 encoding DNA was delivered, BMP-6 expression in the reconstruction sites was significantly enhanced. Micro-computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to significantly enhanced osteointegration in all animals 8 weeks after surgery. Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchymal progenitor cells can effectively improve ligament reconstruction in large animals, thereby addressing a major unmet orthopedic need and offering new possibilities for translation to the clinical setting.
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Affiliation(s)
- Maxim Bez
- Skeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Thomas J Kremen
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Wafa Tawackoli
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Pablo Avalos
- Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Dmitriy Sheyn
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Galina Shapiro
- Skeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel
| | - Joseph C Giaconi
- Department of Imaging, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Shiran Ben David
- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Jess G Snedeker
- Department of Orthopedics, University of Zurich, Zurich 8008, Switzerland
| | - Zulma Gazit
- Skeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Katherine W Ferrara
- Department of Biomedical Engineering, University of California, Davis, Davis, CA 95616, USA
| | - Dan Gazit
- Skeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Orthopedics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Gadi Pelled
- Skeletal Biotech Laboratory, The Hebrew University-Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem 91120, Israel; Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Biomedical Imaging Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
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30
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Converse MI, Walther RG, Ingram JT, Li Y, Yu SM, Monson KL. Detection and characterization of molecular-level collagen damage in overstretched cerebral arteries. Acta Biomater 2018; 67:307-318. [PMID: 29225149 PMCID: PMC5794621 DOI: 10.1016/j.actbio.2017.11.052] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Revised: 11/21/2017] [Accepted: 11/29/2017] [Indexed: 12/22/2022]
Abstract
It is well established that overstretch of arteries alters their mechanics and compromises their function. However, the underlying structural mechanisms behind these changes are poorly understood. Utilizing a recently developed collagen hybridizing peptide (CHP), we demonstrate that a single mechanical overstretch of an artery produces molecular-level unfolding of collagen. In addition, imaging and quantification of CHP binding revealed that overstretch produces damage (unfolding) among fibers aligned with the direction of loading, that damage increases with overstretch severity, and that the onset of this damage is closely associated with tissue yielding. These findings held true for both axial and circumferential loading directions. Our results are the first to identify stretch-induced molecular damage to collagen in blood vessels. Furthermore, our approach is advantageous over existing methods of collagen damage detection as it is non-destructive, readily visualized, and objectively quantified. This work opens the door to revealing additional structure-function relationships in arteries. We anticipate that this approach can be used to better understand arterial damage in clinically relevant settings such as angioplasty and vascular trauma. Furthermore, CHP can be a tool for the development of microstructurally-based constitutive models and experimentally validated computational models of arterial damage and damage propagation across physical scales. STATEMENT OF SIGNIFICANCE Arteries play a critical role by carrying oxygen and essential nutrients throughout the body. However, trauma to the head and neck, as well as surgical interventions, can overstretch arteries and alter their mechanics. In order to better understand the cause of these changes, we employ a novel collagen hybridizing peptide (CHP) to study collagen damage in overstretched arteries. Our approach is unique in that we go beyond the fiber- and fibril-level and characterize molecular-level disruption. In addition, we image and quantify fluorescently-labeled CHP to reveal a new structure-property relationship in arterial damage. We anticipate that our approach can be used to better understand arterial damage in clinically relevant settings such as angioplasty and vascular trauma.
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Affiliation(s)
- Matthew I Converse
- Department of Mechanical Engineering, University of Utah, Salt Lake City, UT 84112, United States
| | - Raymond G Walther
- Department of Mechanical Engineering, University of Utah, Salt Lake City, UT 84112, United States
| | - Justin T Ingram
- Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, United States
| | - Yang Li
- Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, United States
| | - S Michael Yu
- Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, United States; Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, United States
| | - Kenneth L Monson
- Department of Mechanical Engineering, University of Utah, Salt Lake City, UT 84112, United States; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, United States.
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31
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Perrone GS, Proffen BL, Kiapour AM, Sieker JT, Fleming BC, Murray MM. Bench-to-bedside: Bridge-enhanced anterior cruciate ligament repair. J Orthop Res 2017; 35:2606-2612. [PMID: 28608618 PMCID: PMC5729057 DOI: 10.1002/jor.23632] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Accepted: 06/05/2017] [Indexed: 02/04/2023]
Abstract
Anterior cruciate ligament (ACL) injuries are one of the most well-known orthopaedic injuries and are treated with one of the most common orthopaedic procedures performed in the United States. This surgical procedure, ACL reconstruction, is successful at restoring the gross stability of the knee. However, the outcomes of ACL reconstruction can be limited by short and long-term complications, including muscle weakness, graft rupture, and premature osteoarthritis. Thus, new methods of treating this injury are being explored. This review details the pathway of how a tissue engineering strategy can be used to improve the healing of the ACL in preclinical studies and then translated to patients in an FDA-approved clinical study. This review paper will outline the clinical importance of ACL injuries, history of primary repair, the pathology behind failure of the ACL to heal, pre-clinical studies, the FDA approval process for a high risk medical device, and the preliminary results from a first-in-human study. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2606-2612, 2017.
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Affiliation(s)
- Gabriel S Perrone
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
| | - Benedikt L Proffen
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
| | - Ata M Kiapour
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
| | - Jakob T Sieker
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
| | - Braden C Fleming
- Department of Orthopaedics, Bioengineering Labs, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island
| | - Martha M Murray
- Department of Orthopaedic Surgery, Sports Medicine Research Laboratory, Harvard Medical School/Boston Children's Hospital, Boston, Massachusetts
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32
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Evangelopoulos DS, Kohl S, Schwienbacher S, Gantenbein B, Exadaktylos A, Ahmad SS. Collagen application reduces complication rates of mid-substance ACL tears treated with dynamic intraligamentary stabilization. Knee Surg Sports Traumatol Arthrosc 2017; 25:2414-2419. [PMID: 26564213 DOI: 10.1007/s00167-015-3838-7] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Accepted: 10/22/2015] [Indexed: 01/22/2023]
Abstract
PURPOSE Dynamic intraligamentary stabilization was recently proposed as an option for the treatment of acute ACL ruptures. The aim of this study was to investigate the feasibility of the procedure in mid-substance ACL ruptures and examine whether the additional application of a bilayer collagen I/III membrane would provide for a superior outcome. METHODS The study group consisted of patients presenting with a mid-substance ACL rupture undergoing dynamic intraligamentary stabilization using the Ligamys™ device along with application of a collagen I/III membrane to the surface of the ACL (group A, n = 23). The control group comprised a matched series of patients presenting with a mid-substance ACL rupture also treated by dynamic intraligamentary stabilization Ligamys™ repair, however, without additional collagen application (group B, n = 33). Patients were evaluated preoperatively and at 24-month follow-up for stability as well as Tegner and Lysholm scores. Knee laxity was measured as a difference in anterior translation (ΔAP) and pivot shift. Any events occurring during the follow-up period of 24 months were documented. Logistic regression of complications was performed, and adjustment undertaken where necessary. RESULTS A high total complication rate of 78.8 % was noted in group B, compared to group A (8.7 %) (p = 0.002). The addition of a collagen membrane was the only independent prognostic factor associated with reduced complications (OR 8.0, CI 2.0-32.2, p = 0.003, for collagen-free treatment). In group B, 6 patients suffered a re-rupture with subsequent instability requiring secondary hamstring reconstruction surgery, and 11 developed extension loss requiring arthroscopic debridement, whilst in group A, 2 patients required arthroscopic debridement for loss of exension, with no further encountered complication. Median Lysholm score was significantly higher in group A compared to group B (median 100 range 93-100 vs median 95 range 60-100, p = 0.03) at final follow-up. CONCLUSIONS A high complication rate following ACL Ligamys™ repair of mid-substance ruptures was noted. Application of a collagen membrane to the surface of the ACL resulted in a reduced incidence of extension deficit and re-ruptures. The results indicate that solitary ACL Ligamys™ repair does not present an appropriate treatment modality for mid-substance ACL ruptures. Collage application proved to provide healing benefits with superior clinical outcome after ACL repair. LEVEL OF EVIDENCE Case control study, Level III.
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Affiliation(s)
| | - Sandro Kohl
- Department of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, Bern, Switzerland.
| | - Stefan Schwienbacher
- Department of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, Bern, Switzerland
| | - Benjamin Gantenbein
- Institute for Surgical Technology and Biomechanics (ISTB), University of Bern, Bern, Switzerland
| | | | - Sufian S Ahmad
- Department of Orthopaedic Surgery and Traumatology, Inselspital, University of Bern, Bern, Switzerland.,Institute for Surgical Technology and Biomechanics (ISTB), University of Bern, Bern, Switzerland
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Yamamoto Y, Yamaguchi S, Sasho T, Fukawa T, Akatsu Y, Akagi R, Yamaguchi T, Takahashi K, Nagashima K, Takahashi K. Quantitative US Elastography Can Be Used to Quantify Mechanical and Histologic Tendon Healing in a Rabbit Model of Achilles Tendon Transection. Radiology 2017; 283:408-417. [PMID: 28145809 DOI: 10.1148/radiol.2016160695] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Purpose To determine the time-dependent change in strain ratios (SRs) at the healing site of an Achilles tendon rupture in a rabbit model of tendon transection and to assess the correlation between SRs and the mechanical and histologic properties of the healing tissue. Materials and Methods Experimental methods were approved by the institutional animal care and use committee. The Achilles tendons of 24 New Zealand white rabbits (48 limbs) were surgically transected. The SRs of Achilles tendons were calculated by using compression-based quantitative ultrasonographic elastography measurements obtained 2, 4, 8, and 12 weeks after transection. After in vivo elastography, the left Achilles tendon was harvested for mechanical testing of ultimate load, ultimate stress, elastic modulus, and linear stiffness, and the right tendons were harvested for tissue histologic analysis with the Bonar scale. Time-dependent changes in SRs, mechanical parameters, and Bonar scale scores were evaluated by using repeated-measures analysis of variance. The correlation between SRs and each measured variable was evaluated by using the Spearman rank correlation coefficient. Results Mean SRs and Bonar scale values decreased as a function of time after transection, whereas mechanical parameters increased (P < .001). SR correlated with ultimate stress (ρ = 0.68, P <.001,) elastic modulus (ρ = 0.74, P <.001), and the Bonar scale (ρ = 0.87, P <.001). Conclusion Quantitative elastography could be a useful method with which to evaluate mechanical and histologic properties of the healing tendon. © RSNA, 2017 Online supplemental material is available for this article.
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Affiliation(s)
- Yohei Yamamoto
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Satoshi Yamaguchi
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Takahisa Sasho
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Taisuke Fukawa
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Yorikazu Akatsu
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Ryuichiro Akagi
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Tadashi Yamaguchi
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Kenji Takahashi
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Kengo Nagashima
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
| | - Kazuhisa Takahashi
- From the Department of Orthopaedic Surgery, Graduate School of Medical and Pharmaceutical Sciences (Y.Y., S.Y., T.S., T.F., Y.A., R.A., Kazuhisa Takahashi), Clinical Research Center (K.N.), and Center for Frontier Medical Engineering (T.Y.), Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan; and Funabashi Orthopaedic Hospital, Funabashi, Japan (Kenji Takahashi)
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Murray MM, Flutie BM, Kalish LA, Ecklund K, Fleming BC, Proffen BL, Micheli LJ. The Bridge-Enhanced Anterior Cruciate Ligament Repair (BEAR) Procedure: An Early Feasibility Cohort Study. Orthop J Sports Med 2016; 4:2325967116672176. [PMID: 27900338 PMCID: PMC5120682 DOI: 10.1177/2325967116672176] [Citation(s) in RCA: 110] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background: This study assessed the safety of the newly developed bridge-enhanced anterior cruciate ligament (ACL) repair (BEAR), which involves suture repair of the ligament combined with a bioactive scaffold to bridge the gap between the torn ligament ends. As the intra-articular environment is complex in its response to implanted materials, this study was designed to determine whether there would be a significant rate of adverse reaction to the implanted scaffold. Hypothesis: The primary hypothesis was that the implanted scaffold would not result in a deep joint infection (arthrocentesis with positive culture) or significant inflammation (clinical symptoms justifying arthrocentesis but negative culture). The secondary hypotheses were that patients treated with BEAR would have early postoperative outcomes that were similar to patients treated with ACL reconstruction with an autologous hamstring graft. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 20 patients were enrolled in this nonrandomized, first-in-human study. Ten patients received BEAR treatment and 10 received a hamstring autograft ACL reconstruction. The BEAR procedure was performed by augmenting a suture repair with a proprietary scaffold, the BEAR scaffold, placed in between the torn ends of the ACL at the time of suture repair. The BEAR scaffold is to our knowledge the only device that fills the gap between the torn ligament ends to have current Investigational Device Exemption approval from the Food and Drug Administration. Ten milliliters of autologous whole blood were added to the scaffold prior to wound closure. Outcomes were assessed at 3 months postoperatively. The outcomes measures included postoperative pain, muscle atrophy, loss of joint range of motion, and implant failure (designated by an International Knee Documentation Committee grade C or D Lachman test and/or an absence of continuous ACL tissue on magnetic resonance images). Results: There were no joint infections or signs of significant inflammation in either group. There were no differences between groups in effusion or pain, and no failures by Lachman examination criteria (BEAR, 8 grade A and 2 grade B; ACL reconstruction, 10 grade A). Magnetic resonance images from all of the BEAR and ACL-reconstructed patients demonstrated a continuous ACL or intact graft. In addition, hamstring strength at 3 months was significantly better in the BEAR group than in the hamstring autograft group (mean ± SD: 77.9% ± 14.6% vs 55.9% ± 7.8% of the contralateral side; P < .001). Conclusion: The results of this study suggest that the BEAR procedure may have a rate of adverse reactions low enough to warrant a study of efficacy in a larger group of patients.
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Affiliation(s)
- Martha M Murray
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, USA
| | - Brett M Flutie
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, USA
| | - Leslie A Kalish
- Clinical Research Center, Boston Children's Hospital Boston, Massachusetts, USA
| | - Kirsten Ecklund
- Department of Radiology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Braden C Fleming
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Benedikt L Proffen
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, USA
| | - Lyle J Micheli
- Division of Sports Medicine, Department of Orthopaedic Surgery, Boston Children's Hospital Boston, Massachusetts, USA
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Farraro KF, Sasaki N, Woo SLY, Kim KE, Tei MM, Speziali A, McMahon PJ. Magnesium ring device to restore function of a transected anterior cruciate ligament in the goat stifle joint. J Orthop Res 2016; 34:2001-2008. [PMID: 26916011 PMCID: PMC9583724 DOI: 10.1002/jor.23210] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Accepted: 02/18/2016] [Indexed: 02/04/2023]
Abstract
A bioresorbable, mono-crystalline magnesium (Mg) ring device and suture implantation technique were designed to connect the ends of a transected anterior cruciate ligament (ACL) to restabilize the knee and load the ACL to prevent disuse atrophy of its insertion sites and facilitate its healing. To test its application, cadaveric goat stifle joints were evaluated using a robotic/universal force-moment sensor testing system in three states: Intact, ACL-deficient, and after Mg ring repair, at 30°, 60°, and 90° of joint flexion. Under a 67-N anterior tibial load simulating that used in clinical examinations, the corresponding anterior tibial translation (ATT) and in-situ forces in the ACL and medial meniscus for 0 and 100 N of axial compression were obtained and compared with a control group treated with suture repair. In all cases, Mg ring repair reduced the ATT by over 50% compared to the ACL-deficient joint, and in-situ forces in the ACL and medial meniscus were restored to near normal levels, showing significant improvement over suture repair. These findings suggest that Mg ring repair could successfully stabilize the joint and load the ACL immediately after surgery, laying the framework for future in vivo studies to assess its utility for ACL healing. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2001-2008, 2016.
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Affiliation(s)
- Kathryn F. Farraro
- Department of Bioengineering, Musculoskeletal Research Center; Swanson School of Engineering, University of Pittsburgh; 405 Center for Bioengineering, 300 Technology Drive Pittsburgh Pennsylvania 15219
| | - Norihiro Sasaki
- Department of Bioengineering, Musculoskeletal Research Center; Swanson School of Engineering, University of Pittsburgh; 405 Center for Bioengineering, 300 Technology Drive Pittsburgh Pennsylvania 15219
| | - Savio L-Y. Woo
- Department of Bioengineering, Musculoskeletal Research Center; Swanson School of Engineering, University of Pittsburgh; 405 Center for Bioengineering, 300 Technology Drive Pittsburgh Pennsylvania 15219
| | - Kwang E. Kim
- Department of Bioengineering, Musculoskeletal Research Center; Swanson School of Engineering, University of Pittsburgh; 405 Center for Bioengineering, 300 Technology Drive Pittsburgh Pennsylvania 15219
| | - Matteo M. Tei
- Department of Bioengineering, Musculoskeletal Research Center; Swanson School of Engineering, University of Pittsburgh; 405 Center for Bioengineering, 300 Technology Drive Pittsburgh Pennsylvania 15219
| | - Andrea Speziali
- Department of Bioengineering, Musculoskeletal Research Center; Swanson School of Engineering, University of Pittsburgh; 405 Center for Bioengineering, 300 Technology Drive Pittsburgh Pennsylvania 15219
| | - Patrick J. McMahon
- Department of Bioengineering, Musculoskeletal Research Center; Swanson School of Engineering, University of Pittsburgh; 405 Center for Bioengineering, 300 Technology Drive Pittsburgh Pennsylvania 15219
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Cook JL, Smith PA, Bozynski CC, Kuroki K, Cook CR, Stoker AM, Pfeiffer FM. Multiple injections of leukoreduced platelet rich plasma reduce pain and functional impairment in a canine model of ACL and meniscal deficiency. J Orthop Res 2016; 34:607-15. [PMID: 26403590 DOI: 10.1002/jor.23054] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Accepted: 09/21/2015] [Indexed: 02/04/2023]
Abstract
Platelet rich plasma (PRP) is used to treat many musculoskeletal disorders. We used a canine model to determine the effects of multiple intra-articular injections of leukoreduced PRP (ACP) on anterior cruciate ligament healing, meniscal healing, and progression of osteoarthritis (OA). With Animal Care and Use Committee (ACUC) approval, 12 dogs underwent partial ACL transection and meniscal release in one knee. At weeks 1, 2, 3, 6, and 8 after insult, dogs were treated with intra-articular injections (2 ml) of either ACP (n = 6) or saline (n = 6). Dogs were assessed over 6 months to determine comfortable range of motion (CROM), lameness, pain, effusion, kinetics, and radiographic and arthroscopic assessments. At 6-month endpoint, dogs were assessed for ACL material properties and histopathology. Saline-treated dogs had significantly (p < 0.04) more CROM loss, significantly (p < 0.01) more pain, significantly (p < 0.05) more severe lameness, significantly (p < 0.05) lower function, and significantly (p < 0.05) lower %Total Pressure Index in affected hindlimbs compared to ACP-treated dogs. Radiographic OA increased significantly (p < 0.01) over time within each group. Arthroscopically, saline-treated knees showed moderate to severe synovitis, further ACL disruption, and medial compartment cartilage loss, and ACP-treated knees showed evidence of ACL repair and less severe synovitis. ACL material properties in ACP-treated knees were closer to normal than in saline-treated knees, however, the differences were not statistically significant. ACL histopathology was significantly (p< 0.05) less severe in ACP-treated knees compared to saline-treated knees. Five intra-articular injections of leukoreduced PRP had beneficial effects for ACL healing, improved range of motion, decreased pain, and improved limb function for up to 6 months in this model.
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Affiliation(s)
- James L Cook
- Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
| | | | | | - Keiichi Kuroki
- Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
| | - Cristi R Cook
- Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
| | - Aaron M Stoker
- Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
| | - Ferris M Pfeiffer
- Comparative Orthopaedic Laboratory, University of Missouri, Columbia, Missouri
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Taylor SA, Khair MM, Roberts TR, DiFelice GS. Primary Repair of the Anterior Cruciate Ligament: A Systematic Review. Arthroscopy 2015; 31:2233-47. [PMID: 26165465 DOI: 10.1016/j.arthro.2015.05.007] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2014] [Revised: 04/13/2015] [Accepted: 05/13/2015] [Indexed: 02/02/2023]
Abstract
PURPOSE To describe the clinical and preclinical research conducted on primary repair of the anterior cruciate ligament (ACL) during the past 10 years. METHODS A systematic search of PubMed, the Cochrane Central Register of Controlled Trials, and Embase was performed for all English-language studies published between 2003 and April 2014 on primary repair of the ACL. RESULTS Twenty-six studies met the inclusion and exclusion criteria. In the clinical research group, 8 studies (166 patients; age range, 10 to 71 years) met the inclusion and exclusion criteria and were largely long-term clinical outcome studies, based on the original cohorts from the 1970s and 1980s, and suggested high failure rates, additional surgery, and revision for instability. A subset of patients, however, achieved good to excellent subjective and objective long-term outcomes. In the preclinical research group, 18 studies met the inclusion and exclusion criteria and were based on an ACL transection model; they suggested that (1) stabilization of the knee with an internal suture strut improved the healing and biomechanical properties of the repaired ACL, (2) "enhancing" the repair with biological collagen-platelet composite augmentation improved healing and mechanical strength, (3) younger age and skeletal immaturity seem to correlate with improved histologic healing and biomechanical properties, (4) enhanced primary repair of the ACL may reduce post-traumatic osteoarthritis, and (5) the native ACL biomechanically outperformed the repaired ACL. CONCLUSIONS Although long-term human studies suggest collectively unacceptable outcomes for open primary repair of the ACL, a subset of patients achieved acceptable long-term results. ACL transection model animal studies showed improved healing and biomechanics with primary suture repair stabilization, early intervention, biological augmentation techniques, and younger age. Primary repair of the ACL may be an effective treatment modality for an appropriately selected subset of patients. LEVEL OF EVIDENCE Level IV, systematic review of preclinical and clinical Level IV studies.
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Affiliation(s)
- Samuel A Taylor
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - M Michael Khair
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - Timothy R Roberts
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A
| | - Gregory S DiFelice
- Orthopaedic Trauma and Sports Medicine Services, Hospital for Special Surgery, New York, New York, U.S.A..
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Kiapour AM, Fleming BC, Murray MM. Biomechanical Outcomes of Bridge-enhanced Anterior Cruciate Ligament Repair Are Influenced by Sex in a Preclinical Model. Clin Orthop Relat Res 2015; 473:2599-608. [PMID: 25742916 PMCID: PMC4488214 DOI: 10.1007/s11999-015-4226-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Despite the well-established role of sex on the anterior cruciate ligament (ACL) injury risk, its effects on ACL surgical outcomes remain controversial. This is particularly critical when developing novel surgical techniques to treat the injury because there are limited data existing on how these procedures will respond in each sex. One such approach is bridge-enhanced ACL repair, in which primary suture repair of the ACL is augmented with a bioactive scaffold saturated with autologous blood. It has shown comparable biomechanical outcomes to ACL reconstruction in preclinical models. QUESTIONS/PURPOSES We asked (1) whether sex affects the biomechanical outcomes of bridge-enhanced ACL repair; and (2) if suture type (absorbable or nonabsorbable), used to repair the torn ACL, can minimize the potential sex discrepancies in outcomes after 15 weeks of healing in a large animal preclinical model. METHODS Seventeen (eight males, nine females) Yorkshire pigs (Parson's Farms, Hadley, MA, USA) underwent bilateral ACL transection and received bridge-enhanced ACL repair with an absorbable suture (n=17) on one side and with a nonabsorbable suture (n=17) on the other side. The leg receiving the absorbable suture was randomized within each animal. ACL structural properties and AP knee laxity for each knee were measured after 15 weeks of healing. Mixed linear models were used to compare the biomechanical outcomes between sexes and suture groups. RESULTS When treated with absorbable suture, females had a lower ACL linear stiffness (females, 11 N/mm [range, 8-42]; males, 31 N/mm [range, 12-56]; difference, 20 N/mm [95% confidence interval {CI}, 4-36]; p=0.032), ACL yield (females, 121 N [range, 56-316]; males, 224 N [range, 55-538]; difference, 103 N [95% CI, 6-200]; p=0.078), and maximum load (females, 128 N [range, 63-332]; males, 241 N [range, 82-538]; difference, 114 N [95% CI, 15-212]; p=0.052) than males after 15 weeks of healing. Female knees treated with absorbable suture had a lower linear stiffness (absorbable, 11 N/mm [range, 8-42]; nonabsorbable, 25 N/mm [range, 8-64]; difference, 14 [95% CI, 2-26] N; p=0.054), ACL yield (absorbable, 121 N [range, 56-316]; nonabsorbable, 230 N [range, 149-573]; difference, 109 N [95% CI, 56-162]; p=0.002), and maximum load (absorbable, 128 N [range, 63-332]; nonabsorbable, 235 N [range, 151-593]; difference, 107 N [95% CI, 51-163]; p=0.002) along with greater AP knee laxity at 30° (absorbable, 9 mm [range, 5-12]; nonabsorbable, 7 mm [range, 2-13]; difference, 2 mm [95% CI, 1-4]; p=0.034) than females treated with nonabsorbable suture. When repaired using nonabsorbable suture, the biomechanical outcomes were similar between female and male knees (p>0.10). CONCLUSIONS Females had significantly worse biomechanical outcomes than males when the repairs were performed using absorbable sutures. However, the use of nonabsorbable sutures ameliorated these differences between males and females. CLINICAL RELEVANCE The current findings highlight the critical role of sex on the biomechanical outcomes of bridge-enhanced ACL repair in a relevant large animal model. Better understanding of the mechanisms responsible for these observations using preclinical models and concomitant clinical studies in human patients may allow for additional development of sex-specific surgical and rehabilitative strategies with potentially improved outcomes in women.
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Affiliation(s)
- Ata M. Kiapour
- />Sports Medicine Research Laboratory, Department of Orthopaedic Surgery, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115 USA
| | - Braden C. Fleming
- />Department of Orthopaedics, Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, RI USA
| | - Martha M. Murray
- />Sports Medicine Research Laboratory, Department of Orthopaedic Surgery, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115 USA
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Biercevicz AM, Akelman MR, Fadale PD, Hulstyn MJ, Shalvoy RM, Badger GJ, Tung GA, Oksendahl HL, Fleming BC. MRI volume and signal intensity of ACL graft predict clinical, functional, and patient-oriented outcome measures after ACL reconstruction. Am J Sports Med 2015; 43:693-9. [PMID: 25540298 PMCID: PMC4344859 DOI: 10.1177/0363546514561435] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Clinical, functional, and patient-oriented outcomes are commonly used to evaluate the efficacy of treatments after anterior cruciate ligament (ACL) injury; however, these evaluation techniques do not directly measure the biomechanical changes that occur with healing. PURPOSE To determine if the magnetic resonance (MR) image-derived parameters of graft volume and signal intensity (SI), which have been used to predict the biomechanical (ie, structural) properties of the graft in animal models, correlate with commonly used clinical (anteroposterior [AP] knee laxity), functional (1-legged hop), and patient-oriented outcome measures (Knee Injury and Osteoarthritis Outcome Score [KOOS]) in patients 3 and 5 years after ACL reconstruction. STUDY DESIGN Cohort study (diagnosis); Level of evidence, 3. METHODS Based on a subset of participants enrolled in an ongoing ACL reconstruction clinical trial, AP knee laxity, 1-legged hop test, and KOOS were assessed at 3- and 5-year follow-up. Three-dimensional, T1-weighted MR images were collected at each visit. Both the volume and median SI of the healing graft were determined and used as predictors in a multiple regression linear model to predict the traditional outcome measures. RESULTS Graft volume combined with median SI in a multiple linear regression model predicted 1-legged hop test at both the 3- and 5-year follow-up visits (R(2) = 0.40, P = .008 and R(2) = 0.62, P = .003, respectively). Similar results were found at the 5-year follow-up for the KOOS quality of life (R(2) = 0.49, P = .012), sport/function (R(2) = 0.37, P = .048), pain (R(2) = 0.46, P = .017), and symptoms (R(2) = 0.45, P = .021) subscores, although these variables were not significant at 3 years. The multiple linear regression model for AP knee laxity at 5-year follow-up approached significance (R(2) = 0.36, P = .088). CONCLUSION The MR parameters (volume and median SI) used to predict ex vivo biomechanical properties of the graft in an animal model have the ability to predict clinical or in vivo outcome measures in patients at 3- and 5-year follow-up. CLINICAL RELEVANCE Results from this study may enhance clinical evaluation of graft health by relating the MR parameters of volume and median SI to traditional outcome measures and could potentially aid researchers in determining the appropriate timing for athletes to return to sport.
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Affiliation(s)
- Alison M Biercevicz
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Matthew R Akelman
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Paul D Fadale
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Michael J Hulstyn
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Robert M Shalvoy
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Gary J Badger
- Department of Medical Biostatistics, University of Vermont, Burlington, Vermont, USA
| | - Glenn A Tung
- Department of Diagnostic Imaging, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Heidi L Oksendahl
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
| | - Braden C Fleming
- Department of Orthopaedics, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, Rhode Island, USA
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Biercevicz AM, Akelman MR, Rubin LE, Walsh EG, Merck D, Fleming BC. The uncertainty of predicting intact anterior cruciate ligament degeneration in terms of structural properties using T(2)(*) relaxometry in a human cadaveric model. J Biomech 2015; 48:1188-92. [PMID: 25746575 DOI: 10.1016/j.jbiomech.2015.02.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 01/15/2015] [Accepted: 02/15/2015] [Indexed: 11/26/2022]
Abstract
The combination of healing anterior cruciate ligament (ACL) volume and the distributions of T2(*) relaxation times within it have been shown to predict the biomechanical failure properties in a porcine model. This MR-based prediction model has not yet been used to assess ligament degeneration in the aging human knee. Using a set of 15 human cadaveric knees of varying ages, we obtained in situ MR measures of volume and T2(*) of the intact ACL and then related these MR variables to biomechanical outcomes (maximum and yield loads, linear stiffness) obtained via ex vivo failure testing. Using volume in conjunction with the median T2(*) value, the multiple linear regression model did not predict maximum failure load for the intact human ACL; R(2)=0.23, p=0.200. Similar insignificant results were found for yield load and linear stiffness. Naturally restricted distributions of the intact ligament volume and T2(*) (demonstrated by the respective Z-scores) in an older cadaveric population were the likely reason for the insignificant results. These restricted distributions may negatively affect the ability to detect a correlation when one exists. Further research is necessary to understand the relationship of MRI variables and ligament degeneration. While this study failed to find a significant prediction of human biomechanical outcome using these MR variables, with further research, an MR-based approach may offer a tool to longitudinally assess changes in cruciate ligament degradation.
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Affiliation(s)
- A M Biercevicz
- Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI, USA; Center for Biomedical Engineering and School of Engineering, Brown University, Providence, RI, USA
| | - M R Akelman
- Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI, USA
| | - L E Rubin
- Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI, USA
| | - E G Walsh
- Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, RI, USA
| | - D Merck
- Center for Biomedical Engineering and School of Engineering, Brown University, Providence, RI, USA; Department of Diagnostic Imaging, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI, USA
| | - B C Fleming
- Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI, USA; Center for Biomedical Engineering and School of Engineering, Brown University, Providence, RI, 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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Biercevicz AM, Walsh EG, Murray MM, Akelman MR, Fleming BC. Improving the clinical efficiency of T2(*) mapping of ligament integrity. J Biomech 2014; 47:2522-5. [PMID: 24792580 DOI: 10.1016/j.jbiomech.2014.03.037] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Revised: 03/21/2014] [Accepted: 03/22/2014] [Indexed: 10/25/2022]
Abstract
Current MR methods use T2(*) relaxation time as a surrogate measure of ligament strength. Currently, a multi-echo voxel-wise least squares fit is the gold standard to create T2(*) maps; however, the post-processing is time-intensive and serves as a stopgap for clinical use. The study objective was to determine if an alternative method could improve post-processing time without sacrificing fidelity of T2(*) values for eventual translational use in the clinic. Using a 6 echo FLASH sequence, three different methods were used to determine intact posterior cruciate ligament (PCL) median T2(*) Two of these methods utilized a voxel-wise method to establish T2(*) maps: (1) a current "gold standard" method using a voxel-wise 6 echo least-squares fit (6LS) and (2) a voxel-wise 2 echo point T2(*) determination (2MM). The third method used median ligament signal intensity and a single nonlinear least-squares fit (6LSROI) instead of a voxel-wise basis. The resulting median T2(*) values of the PCL and computational time were compared. The median T2(*) values were 42% higher using the 2MM compared to the 6LS method (p<0.0001). However, a strong correlation was found for the median T2(*) values between the 2MM and 6LS methods (R(2)=0.80). The median T2(*) values were not significantly different between the 6LS and 6LSROI methods (p=0.519). Using the 2MM (which provides a regional map) and the 6LSROI (which efficiently provides the median T2(*) value) methods in tandem would take only minutes of post-processing computational time compared to the 6LS method (~540 min), and hence would facilitate clinical application of T2(*) maps to predict ligament structural properties as a patient outcome measure.
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Affiliation(s)
- A M Biercevicz
- Department of Orthopaedics, Warren Alpert Medical School, Brown University, 1 Hoppin St, Coro West, Ste 404, Providence, RI 02903, USA
| | - E G Walsh
- Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, RI, USA
| | - M M Murray
- Department of Orthopaedic Surgery, Children׳s Hospital Boston, Boston, MA, USA
| | - M R Akelman
- Department of Orthopaedics, Warren Alpert Medical School, Brown University, 1 Hoppin St, Coro West, Ste 404, Providence, RI 02903, USA
| | - B C Fleming
- Department of Orthopaedics, Warren Alpert Medical School, Brown University, 1 Hoppin St, Coro West, Ste 404, Providence, RI 02903, USA.
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Monto RR. Platelet-rich plasma efficacy versus corticosteroid injection treatment for chronic severe plantar fasciitis. Foot Ankle Int 2014; 35:313-8. [PMID: 24419823 DOI: 10.1177/1071100713519778] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Chronic plantar fasciitis is a common orthopedic condition that can prove difficult to successfully treat. In this study, autologous platelet-rich plasma (PRP), a concentrated bioactive blood component rich in cytokines and growth factors, was compared to traditional cortisone injection in the treatment of chronic cases of plantar fasciitis resistant to traditional nonoperative management. METHODS Forty patients (23 females and 17 males) with unilateral chronic plantar fasciitis that did not respond to a minimum of 4 months of standardized traditional nonoperative treatment modalities were prospectively randomized and treated with either a single ultrasound guided injection of 3 cc PRP or 40 mg DepoMedrol cortisone. American Orthopedic Foot and Ankle Society (AOFAS) hindfoot scoring was completed for all patients immediately prior to PRP or cortisone injection (pretreatment = time 0) and at 3, 6, 12, and 24 months following injection treatment. Baseline pretreatment radiographs and MRI studies were obtained in all cases to confirm the diagnosis of plantar fasciitis. RESULTS The cortisone group had a pretreatment average AOFAS score of 52, which initially improved to 81 at 3 months posttreatment but decreased to 74 at 6 months, then dropped to near baseline levels of 58 at 12 months, and continued to decline to a final score of 56 at 24 months. In contrast, the PRP group started with an average pretreatment AOFAS score of 37, which increased to 95 at 3 months, remained elevated at 94 at 6 and 12 months, and had a final score of 92 at 24 months. CONCLUSIONS PRP was more effective and durable than cortisone injection for the treatment of chronic recalcitrant cases of plantar fasciitis. LEVEL OF EVIDENCE Level I, prospective randomized comparative series.
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Biercevicz AM, Murray MM, Walsh EG, Miranda DL, Machan JT, Fleming BC. T2 * MR relaxometry and ligament volume are associated with the structural properties of the healing ACL. J Orthop Res 2014; 32:492-9. [PMID: 24338640 PMCID: PMC3946219 DOI: 10.1002/jor.22563] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 11/19/2013] [Indexed: 02/04/2023]
Abstract
Our objective was to develop a non-invasive magnetic resonance (MR) method to predict the structural properties of a healing anterior cruciate ligament (ACL) using volume and T2 * relaxation time. We also compared our T2 *-based structural property prediction model to a previous model utilizing signal intensity, an acquisition-dependent variable. Surgical ACL transection followed by no treatment (i.e., natural healing) or bio-enhanced ACL repair was performed in a porcine model. After 52 weeks of healing, high-resolution MR images of the ACL tissue were collected. From these images, ligament volumes and T2 * maps were established. The structural properties of the ligaments were determined via tensile testing. Using the T2 * histogram profile, each ligament voxel was binned based on its T2 * value into four discrete tissue sub-volumes defined by specific T2 * intervals. The linear combination of the ligament sub-volumes binned by T2 * value significantly predicted maximum load, yield load, and linear stiffness (R(2) = 0.92, 0.82, 0.88; p < 0.001) and were similar to the previous signal intensity based method. In conclusion, the T2 * technique offers a highly predictive methodology that is a first step towards the development of a method that can be used to assess ligament healing across scanners, studies, and institutions.
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Affiliation(s)
- Alison M. Biercevicz
- Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI
| | - Martha M. Murray
- Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA
| | - Edward G. Walsh
- Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, RI
| | - Danny L. Miranda
- Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI
| | - Jason T. Machan
- Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI,Biostatistics, Rhode Island Hospital, Providence, RI
| | - Braden C. Fleming
- Department of Orthopaedics, Warren Alpert Medical School, Brown University/Rhode Island Hospital, Providence, RI,School of Engineering, Brown University, Providence, RI 02903
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Murray MM, Fleming BC. Biology of anterior cruciate ligament injury and repair: Kappa delta ann doner vaughn award paper 2013. J Orthop Res 2013; 31:1501-6. [PMID: 23818453 PMCID: PMC3750083 DOI: 10.1002/jor.22420] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Accepted: 06/06/2013] [Indexed: 02/04/2023]
Abstract
Anterior cruciate ligament (ACL) injuries are currently treated by removing the injured ligament and replacing it with a tendon graft. Recent studies have examined alternative treatment methods, including repair and regeneration of the injured ligament. In order to make such an approach feasible, a basic understanding of ACL biology and its response to injury is needed. Identification of obstacles to native ACL healing can then be identified and potentially resolved using tissue engineering strategies-first, with in vitro screening assays, and then with in vivo models of efficacy and safety. This Perspectives paper outlines this path of discovery for optimizing ACL healing using a bio-enhanced repair technique. This journey required constructing indices of the functional tissue response, pioneering physiologically based methods of biomechanical testing, developing, and validating clinically relevant animal models, and creating and optimizing translationally feasible scaffolds, surgical techniques, and biologic additives. Using this systematic translational approach, "bio-enhanced" ACL repair has been advanced to the point where it may become an option for future treatment of acute ACL injuries and the prevention of subsequent post-traumatic osteoarthritis associated with this injury.
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Affiliation(s)
- Martha Meaney Murray
- Department of Orthopaedic Surgery, Boston Children's Hospital, Harvard Medical School, Division of Sports Medicine, Boston, MA
| | - Braden C. Fleming
- Department of Orthopaedics, Bioengineering Labs, Warren Alpert Medical School of Brown University/Rhode Island Hospital, Providence, RI,Center for Biomedical Engineering, Brown University, Providence, RI
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Murray MM, Fleming BC. Use of a bioactive scaffold to stimulate anterior cruciate ligament healing also minimizes posttraumatic osteoarthritis after surgery. Am J Sports Med 2013; 41:1762-70. [PMID: 23857883 PMCID: PMC3735821 DOI: 10.1177/0363546513483446] [Citation(s) in RCA: 143] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although anterior cruciate ligament (ACL) reconstruction is the treatment gold standard for ACL injury, it does not reduce the risk of posttraumatic osteoarthritis. Therefore, new treatments that minimize this postoperative complication are of interest. Bioenhanced ACL repair, in which a bioactive scaffold is used to stimulate healing of an ACL transection, has shown considerable promise in short-term studies. The long-term results of this technique and the effects of the bioenhancement on the articular cartilage have not been previously evaluated in a large animal model. HYPOTHESES (1) The structural (tensile) properties of the porcine ACL at 6 and 12 months after injury are similar when treated with bioenhanced ACL repair, bioenhanced ACL reconstruction, or conventional ACL reconstruction, and all treatments yield results superior to untreated ACL transection. (2) After 1 year, macroscopic cartilage damage following bioenhanced ACL repair is similar to that in bioenhanced ACL reconstruction and less than in conventional ACL reconstruction and untreated ACL transection. STUDY DESIGN Controlled laboratory study. METHODS A total of 64 Yucatan mini-pigs underwent ACL transection and randomization to 4 experimental groups: no treatment, conventional ACL reconstruction, bioenhanced ACL reconstruction using a bioactive scaffold, and bioenhanced ACL repair using a bioactive scaffold. The biomechanical properties of the ligament or graft were examined and macroscopic assessments of the cartilage surfaces were performed after 6 and 12 months of healing. RESULTS The structural properties (ie, linear stiffness, yield, and maximum loads) of the ligament after bioenhanced ACL repair were not significantly different from those in bioenhanced ACL reconstruction or conventional ACL reconstruction but were significantly greater than those in untreated ACL transection after 12 months of healing. Macroscopic cartilage damage after bioenhanced ACL repair was significantly less than that in untreated ACL transection and bioenhanced ACL reconstruction, and there was a strong trend (P = .068) for less macroscopic cartilage damage than in conventional ACL reconstruction in the porcine model at 12 months. CONCLUSION Bioenhanced ACL repair produces a ligament that is biomechanically similar to an ACL graft and provides chondroprotection to the joint after ACL surgery. CLINICAL RELEVANCE Bioenhanced ACL repair may provide a new, less invasive treatment option that reduces cartilage damage following joint injury.
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Affiliation(s)
- Martha M. Murray
- Department of Orthopaedic Surgery, Children’s Hospital Boston, 300 Longwood Ave, Boston, MA 02115
| | - Braden C. Fleming
- Department of Orthopaedics, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Coro West, Suite 404, 1 Hoppin St, Providence RI 02903
,School of Engineering, Brown University, Providence, RI 02903
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Biercevicz AM, Miranda DL, Machan JT, Murray MM, Fleming BC. In Situ, noninvasive, T2*-weighted MRI-derived parameters predict ex vivo structural properties of an anterior cruciate ligament reconstruction or bioenhanced primary repair in a porcine model. Am J Sports Med 2013; 41:560-6. [PMID: 23348076 PMCID: PMC3593999 DOI: 10.1177/0363546512472978] [Citation(s) in RCA: 95] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Magnetic resonance imaging (MRI) is a noninvasive technology that can quantitatively assess anterior cruciate ligament (ACL) graft size and signal intensity. However, how those properties relate to reconstructed or repaired ligament strength during the healing process is yet unknown. HYPOTHESIS Magnetic resonance imaging-derived measures of graft volume and signal intensity are significant predictors of the structural properties of an ACL or ACL graft after 15 weeks and 52 weeks of healing. STUDY DESIGN Controlled laboratory study. METHODS The current data were gathered from 2 experiments evaluating ACL reconstruction and repair techniques. In the first experiment, pigs underwent unilateral ACL transection and received (1) ACL reconstruction, (2) ACL reconstruction with collagen-platelet composite (CPC), or (3) no treatment. The surgical legs were harvested after 15 weeks of healing. In the second experiment, pigs underwent ACL transection and received (1) ACL reconstruction, (2) ACL reconstruction with CPC, (3) bioenhanced ACL primary repair with CPC, or (4) no treatment. The surgical legs were harvested after 52 weeks. The harvested knees were imaged using a T2*-weighted 3-dimensional constructive interference in steady state (CISS) sequence. Each ligament was segmented from the scans, and the intra-articular volume and the median grayscale values were determined. Mechanical testing was performed to establish the ligament structural properties. RESULTS Volume significantly predicted the structural properties (maximum load, yield load, and linear stiffness) of the ligaments and grafts (R (2) = 0.56, 0.56, and 0.49, respectively; P ≤ .001). Likewise, the median grayscale values (ie, signal intensity) significantly predicted the structural properties of the ligaments and grafts (R (2) = 0.42, 0.37, and 0.40, respectively; P < .001). The combination of these 2 parameters in a multiple regression model improved the predictions (R (2) = 0.73, 0.72, and 0.68, respectively; P ≤ .001). CONCLUSION Volume and grayscale values from high-resolution T2*-weighted MRI scans are predictive of structural properties of the healing ligament or graft in a porcine model. CLINICAL RELEVANCE This study provides a critical step in the development of a noninvasive method to predict the structural properties of the healing ACL graft or repair. This technique may prove beneficial as a surrogate outcome measure in preclinical animal and clinical studies.
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Affiliation(s)
| | | | | | - Martha M. Murray
- Dept of Orthopaedic Surgery, Children’s Hospital Boston, Boston MA
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Vavken P, Proffen B, Peterson C, Fleming BC, Machan JT, Murray MM. Effects of suture choice on biomechanics and physeal status after bioenhanced anterior cruciate ligament repair in skeletally immature patients: a large-animal study. Arthroscopy 2013. [PMID: 23200845 PMCID: PMC3644616 DOI: 10.1016/j.arthro.2012.07.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
PURPOSE The objective of this study was to assess the effect of absorbable or nonabsorbable sutures in bioenhanced anterior cruciate ligament (ACL) repair in a skeletally immature pig model on suture tunnel and growth plate healing and biomechanical outcomes. METHODS Sixteen female skeletally immature Yorkshire pigs were randomly allocated to receive unilateral, bioenhanced ACL repair with an absorbable (Vicryl) or nonabsorbable (Ethibond) suture augmented by an extracellular matrix-based scaffold (MIACH). After 15 weeks of healing, micro-computed tomography was used to measure residual tunnel diameters and growth plate status, and biomechanical outcomes were assessed. RESULTS At 15 weeks postoperatively, there was a significant difference in tunnel diameter with significantly larger diameters in the nonabsorbable suture group (4.4 ± 0.3 mm; mean ± SD) than in the absorbable group (1.8 ± 0.5 mm; P < .001). The growth plate showed a significantly greater affected area in the nonabsorbable group (15.2 ± 3.4 mm(2)) than in the absorbable group (2.7 ± 0.8 mm(2), P < .001). There was no significant difference in the linear stiffness of the repairs (29.0 ± 14.8 N/mm for absorbable v 43.3 ± 28.3 N/mm for nonabsorbable sutures, P = .531), but load to failure was higher in the nonabsorbable suture group (211 ± 121.5 N) than in the absorbable suture group (173 ± 101.4 N, P = .002). There was no difference between the 2 groups in anteroposterior laxity at 30° (P = .5117), 60° (P = .3150), and 90° (P = .4297) of knee flexion. CONCLUSIONS The use of absorbable sutures for ACL repair resulted in decreased physeal plate damage after 15 weeks of healing; however, use of nonabsorbable sutures resulted in 20% stronger repairs. CLINICAL RELEVANCE Choice of suture type for ACL repair or repair of tibial avulsion fractures may depend on patient skeletal age and size, with absorbable sutures preferred in very young, small patients at higher risk with physeal damage and nonabsorbable sutures preferred in larger, prepubescent patients who may place higher loads on the repair.
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Affiliation(s)
- Patrick Vavken
- Sports Medicine Research Laboratory, Department of Orthopedic Surgery, Children's Hospital Boston, Harvard Medical School, Massachusetts, USA.
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Proffen BL, McElfresh M, Fleming BC, Murray MM. A comparative anatomical study of the human knee and six animal species. Knee 2012; 19:493-9. [PMID: 21852139 PMCID: PMC3236814 DOI: 10.1016/j.knee.2011.07.005] [Citation(s) in RCA: 258] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2011] [Revised: 06/03/2011] [Accepted: 07/17/2011] [Indexed: 02/02/2023]
Abstract
PURPOSE Animal models are an indispensable tool for developing and testing new clinical applications regarding the treatment of acute injuries and chronic diseases of the knee joint. Therefore, the purpose of this study was to compare the anatomy of the intra-articular structures of the human knee to species commonly used in large animal research studies. METHODS Fresh frozen cow (n=4), sheep (n=3), goat (n=4), dog (n=4), pig (n=5), rabbit (n=5), and human (n=4) cadaveric knees were used. Passive range of motion and intra-articular structure sizes of the knees were measured, the structure sizes normalized to the tibial plateau, and compared among the species. RESULTS Statistically significant differences in the range of motion and intra-articular structure sizes were found among all the species. Only the human knee was able to attain full extension. After normalization, only the pig ACL was significantly longer than the human counterpart. The tibial insertion site of the ACL was split by the anterior lateral meniscus attachment in the cow, sheep, and pig knees. The sheep PCL had two distinct tibial insertion sites, while all the other knees had only one. Furthermore, only in human knees, both lateral meniscal attachments were located more centrally than the medial meniscal attachments. CONCLUSIONS/CLINICAL RELEVANCE Despite the relatively preserved dimensions of the cruciate ligaments, menisci, and intercondylar notch amongst human and animals, structural differences in the cruciate ligament attachment sites and morphology of the menisci between humans and animals are important to consider when selecting an animal model.
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Affiliation(s)
- Benedikt L Proffen
- Department of Orthopaedic Surgery, Children's Hospital of Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA 02115, USA.
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