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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_13 | Pages 45 - 45
1 Nov 2021
Ramirez SC Stoker A Cook J Ma R
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Introduction and Objective. Anterior cruciate ligament reconstruction (ACLR) with tendon autografts is the “gold standard” technique for surgical treatment of ACL injuries. Common tendon graft choices include patellar tendon (PT), semitendinosus/gracilis “hamstring” tendon (HT), or quadriceps tendon (QT). Healing of the graft after ACLR may be affected by graft type since the tissue is subjected to mechanical stresses during post-operative rehabilitation that play important roles in graft integration, remodeling and maturation. Abnormal mechanical loading can result in high inflammatory and degradative processes and altered extracellular matrix (ECM) synthesis and remodeling, potentially modifying tissue structure, composition, and function. Because of the importance of load and ligamentization for tendon autografts, this study was designed to compare the differential inflammatory and degradative metabolic responses to loading by three tendon types commonly used for autograft ACL reconstruction. Materials and Methods. With IRB approval (IRB # 2009879) and informed patient consent, portions of 9 QT, 7 PT and 6 HT were recovered at the time of standard of care ACLR surgeries. Tissues were minced and digested in 0.2 mg/ml collagenase solution for two hours and were then cultured in 10% FBS at 5% CO. 2. , 37°C, and 95% humidity. Once confluent, cells were plated in Collagen Type I-coated BioFlex® plates (1 × 10. 5. cells/well) and cultured for 2 days prior to the application of strain. Then, media was changed to supplemented DMEM with 2% FBS for the application of strain. Fibroblasts were subjected to continuous mechanical stimulation (2-s strain and 10-s relaxation at a 0.5 Hz frequency) at three different elongation strains (mechanical stress deprivation-0%, physiologic strain-4%, and supraphysiological strain-10%). 9. for 6 days using the Flexcell FX-4000T strain system. Media was tested for inflammatory biomarkers (PGE2, IL-8, Gro-α, and MCP-1) and degradation biomarkers (GAG content, MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2). Significant (p<0.05) difference between graft sources were assessed with Kruskal-Wallis test and post-hoc analysis. Results are reported as median± interquartile range (IQR). Results. Differences in Inflammation-Related Biomarker Production (Figure 1): The production of PGE2 was significantly lower by HT fibroblasts compared to both QT and PT fibroblasts at all timepoints and strain levels. The production of Gro-α was significantly lower by HT fibroblasts compared to QT at all time points and strain levels, and significantly lower than PT on day 3 at 0% strain, and all strain levels on day 6. The production of IL-8 by PT fibroblasts was significantly lower than QT and HT fibroblast on day 3 at 10% strain. Differences in Degradation-Related Biomarker Production (Figure 2): The production of GAG by HT fibroblasts was significantly higher compared to both QT and PT fibroblasts on day 6 at 0% strain. The production of MMP-1 by the QT fibroblasts was significantly higher compared to HT fibroblasts on day 3 of culture at all strain levels, and in the 0% and 10% strain levels on day 6 of culture. The production of MMP-1 by the QT fibroblasts was significantly higher compared to PT fibroblasts at in the 0% and 4% strain groups on day 3 of culture. The production of TIMP-1 by the HT fibroblasts was significantly lower compared to PT fibroblasts on day 3 of culture. Conclusions. The results of this study identify potentially clinically relevant difference in the metabolic responses of tendon graft fibroblasts to strain, suggesting a lower inflammatory response by hamstring tendon fibroblasts and higher degradative response by quadriceps tendon fibroblasts. These responses may influence ACL autograft healing as well as inflammatory mediators of pain in the knee after reconstruction, which may have implications regarding graft choice and design of postoperative rehabilitation protocols for optimizing outcomes for patients undergoing ACL reconstruction. For any figures or tables, please contact the authors directly


Aims

Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells.

Methods

Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Scx, TNC) expression were investigated using coculture system.


Bone & Joint Research
Vol. 8, Issue 6 | Pages 232 - 245
1 Jun 2019
Lu C Zhang T Reisdorf RL Amadio PC An K Moran SL Gingery A Zhao C

Objectives

Re-rupture is common after primary flexor tendon repair. Characterization of the biological changes in the ruptured tendon stumps would be helpful, not only to understand the biological responses to the failed tendon repair, but also to investigate if the tendon stumps could be used as a recycling biomaterial for tendon regeneration in the secondary grafting surgery.

Methods

A canine flexor tendon repair and failure model was used. Following six weeks of repair failure, the tendon stumps were analyzed and characterized as isolated tendon-derived stem cells (TDSCs).


The Bone & Joint Journal
Vol. 100-B, Issue 3 | Pages 271 - 284
1 Mar 2018
Hexter AT Thangarajah T Blunn G Haddad FS

Aims

The success of anterior cruciate ligament reconstruction (ACLR) depends on osseointegration at the graft-tunnel interface and intra-articular ligamentization. Our aim was to conduct a systematic review of clinical and preclinical studies that evaluated biological augmentation of graft healing in ACLR.

Materials and Methods

In all, 1879 studies were identified across three databases. Following assessment against strict criteria, 112 studies were included (20 clinical studies; 92 animal studies).


Bone & Joint Research
Vol. 6, Issue 7 | Pages 399 - 404
1 Jul 2017
Sun X Liu W Cheng G Qu X Bi H Cao Z Yu Q

Objectives

The injured anterior cruciate ligament (ACL) is thought to exhibit an impaired healing response, and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta 1 (TGF-β1).

Methods

A rabbit ACL injury model was used to study the effect of CTGF on ligament recovery. Quantitative real-time PCR (qRT-PCR) was performed for detection of changes in RNA levels of TGF-β1, type 1 collagen (COL1), type 2 collagen (COL2), SRY-related high mobility group-box gene9 (SOX9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase 13 (MMP-13). Expression of related proteins was detected by Western blotting.


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 793 - 798
1 Jun 2016
Kohl S Evangelopoulos DS Schär MO Bieri K Müller T Ahmad SS

Aims

The purpose of this study was to report the experience of dynamic intraligamentary stabilisation (DIS) using the Ligamys device for the treatment of acute ruptures of the anterior cruciate ligament (ACL).

Patients and Methods

Between March 2011 and April 2012, 50 patients (34 men and 16 women) with an acute rupture of the ACL underwent primary repair using this device. The mean age of the patients was 30 years (18 to 50). Patients were evaluated for laxity, stability, range of movement (ROM), Tegner, Lysholm, International Knee Documentation Committee (IKDC) and visual analogue scale (VAS) scores over a follow-up period of two years.


Bone & Joint Research
Vol. 3, Issue 2 | Pages 20 - 31
1 Feb 2014
Kiapour AM Murray MM

Injury to the anterior cruciate ligament (ACL) is one of the most devastating and frequent injuries of the knee. Surgical reconstruction is the current standard of care for treatment of ACL injuries in active patients. The widespread adoption of ACL reconstruction over primary repair was based on early perception of the limited healing capacity of the ACL. Although the majority of ACL reconstruction surgeries successfully restore gross joint stability, post-traumatic osteoarthritis is commonplace following these injuries, even with ACL reconstruction. The development of new techniques to limit the long-term clinical sequelae associated with ACL reconstruction has been the main focus of research over the past decades. The improved knowledge of healing, along with recent advances in tissue engineering and regenerative medicine, has resulted in the discovery of novel biologically augmented ACL-repair techniques that have satisfactory outcomes in preclinical studies. This instructional review provides a summary of the latest advances made in ACL repair.

Cite this article: Bone Joint Res 2014;3:20–31.


Bone & Joint Research
Vol. 1, Issue 10 | Pages 238 - 244
1 Oct 2012
Naraoka T Ishibashi Y Tsuda E Yamamoto Y Kusumi T Kakizaki I Toh S

Objectives

This study aimed to investigate time-dependent gene expression of injured human anterior cruciate ligament (ACL), and to evaluate the histological changes of the ACL remnant in terms of cellular characterisation.

Methods

Injured human ACL tissues were harvested from 105 patients undergoing primary ACL reconstruction and divided into four phases based on the period from injury to surgery. Phase I was < three weeks, phase II was three to eight weeks, phase III was eight to 20 weeks, and phase IV was ≥ 21 weeks. Gene expressions of these tissues were analysed in each phase by quantitative real-time polymerase chain reaction using selected markers (collagen types 1 and 3, biglycan, decorin, α-smooth muscle actin, IL-6, TGF-β1, MMP-1, MMP-2 and TIMP-1). Immunohistochemical staining was also performed using primary antibodies against CD68, CD55, Stat3 and phosphorylated-Stat3 (P-Stat3).


Bone & Joint Research
Vol. 1, Issue 9 | Pages 218 - 224
1 Sep 2012
Tabuchi K Soejima T Kanazawa T Noguchi K Nagata K

Objectives

The purpose of this study was to evaluate chronological changes in the collagen-type composition at tendon–bone interface during tendon–bone healing and to clarify the continuity between Sharpey-like fibres and inner fibres of the tendon.

Methods

Male white rabbits were used to create an extra-articular bone–tendon graft model by grafting the extensor digitorum longus into a bone tunnel. Three rabbits were killed at two, four, eight, 12 and 26 weeks post-operatively. Elastica van Gieson staining was used to colour 5 µm coronal sections, which were examined under optical and polarised light microscopy. Immunostaining for type I, II and III collagen was also performed.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 103 - 103
1 Feb 2012
Robinson J Baudot C Colombet P Thoribé B Paris G
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There are a few papers in the literature to indicate the likely functional outcome of conservatively managed sportsmen in whom primary outcome cruciate ligament [ACL] healing occurs. We reviewed 298 sportsmen presenting with isolated ACL rupture that were conservatively managed with a rehabilitation programme, based on regaining proprioceptive and hamstring control, and aimed at achieving primary ACL healing. All were protected in a hinged brace. In 50 patients, the ACL was determined as having healed clinically; these patients underwent instrumented laximetry testing with KT 1000 arthrometry and were determined: IKDC A [Normal] or IKDC B [nearly normal]. An MRI was also performed which confirmed healing in 39 patients with ACL fibres parallel to Blumenstat's line. In 11 patients the ACL stump had healed to the PCL. The 50 patients were followed up for an average 16 months [range, 14 to 17 months]. 56% of patients suffered recurrent instability when they returned to their preinjury level of contact or pivoting sport. For competitive athletes, 76.5% suffered further instability on return to sport despite the four-month rehabilitation and independent arthrometry score or MRI findings. However, for occasional, recreational athletes only 7% suffered recurrent instability. This study suggests that a rehabilitation programme aimed at primary ACL healing affords satisfactory results for the occasional, recreational athlete but does not achieve the quality of restraint sufficient for contact or pivoting sports in competitive athletes. These patients suffer high levels of recurrent instability and are exposed to the risk of secondary chondral and meniscal injury


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 267 - 267
1 May 2009
Gobbi A Ramces F Arrigoni P
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Introduction: recent studies showed the possibility of spontaneous ACL healing in acute lesion with proper treatment. The goal of our study was to analyze the functional outcome of partial ACL tears treated acutely with suture-repair combined with a bone marrow stimulation (BMS) technique (microperforation). We hypothesized that knee stability could be restored and good functional outcome could be obtained with a simple primary repair technique. Methods: From January 2003 to January 2006, 22 patients (14 males and 8 females – mean age: 23 years) with partial ACL rupture underwent acute primary ACL repair with our technique. Inclusion-exclusion criteria:. anterior instability (confirmed intraoperatively by an isolated ACL tear),. surgery performed within 3 weeks from injury. No grade 4 chondral defect,. no associated pathologies except for meniscal lesion. will to undergo to the same rehabilitation protocol. Parameters analyzed included the standard knee scales (IKDC, Noyes, Lysholm and Tegner), SANE Score, Knee Laxity Analysis and Deep Flexion Tests. In 6 cases, second look arthroscopy was performed. All patients underwent a post-operative MRI. Results: All these patients were available for follow up at 3/6 and final follow up (average of 18 months). Scoring systems revealed: Lysholm 93% (74–100), Tegner 7 (6–9), Noyes 80% (60–100) and Subjective (SANE) 86,22% (60–100). IKDC score demonstrated 55% group A, 36% B, 4% C and 4% D. This last patient didn’t go back to his previous activity level because of subjective apprehension. The knee was stable. Pivot shift test was negative in all the cases. Side to side difference was less or equal to 2 mm in all of our patients. Conclusion: Based on the preliminary results, primary ACL repair with BMS can lead to favourable results in acute partial ACL lesion. However, further prospective randomized studies are recommended at longer follow-up to validate these findings


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 288 - 288
1 May 2009
Horan RL Richmond JC Weitzel PP Horan DJ Mortarino E DeAngelis N Toponarski I Huang J Boepple H Prudom J Altman GH
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Objectives: Advances in biomedical engineering have led to a thorough understanding of the body’s own capacity for ACL healing if provided the correct impetus—a long-term bioresorbable graft scaffold that anticipates the defect site’s biological and mechanical requirements. We hypothesize that by providing a structural scaffold which anticipates ACL repair mechanisms, “engineered” autologous ligament with excellent functional integrity can be developed by the body itself. This study evaluated the SeriACL™ graft, a non-mammalian derived long-term bioresorbable multi-bundled silk-based implant, for ACL replacement in a goat model at 3, 6 and 12 months post-operatively. Methods: The ACL of 43 goats was replaced with the SeriACL graft in an arthroscopically assisted procedure. The ACL was excised, a guide pin driven into the femur and 6mm diameter antegrade drilling performed. The tibial tunnel was drilled under direct visualization. The SeriACL, designed to mimic hamstring grafts, was anchored around a post on the femur. The graft was tensioned to 50N and cycled 30x before tibial fixation with a staple and sutures around a post. Animals were clinically, mechanically and histomorphometrically evaluated at 3, 6 and 12 months. Results: The SeriACL graft or surgical procedure did not induce early signs of acute inflammation, swelling or initial scar formation as indicated by rapidly declining scores for pain and knee size. All animals were weight bearing at 3, 6 and 12 months, with 95% returning to normal gait by 6 months. Lachmann showed the majority of knees were clinically stable at all points. Range of motion assessment indicated the knees maintained a normal range flexion and extension at all points. No gross cartilaginous damage, synovitis or particulate debris in lymph nodes was observed at any time point. Organized collagen and aligned fibroblasts in a crimp pattern were observed in the periphery of the ligament structure, adjacent to and attached to the remaining SeriACL device at all necropsy times. Collagen development throughout the graft and bone tunnels increased with time. Conversely, inflammation and device mass loss decreased with time. Fluoroscopy indicated no abnormal bone tunnel findings. Total plasma IgG levels did not increase from pre-surgery levels at any time. AP laxity indicated joint stability at all time points. Implant abrasion was observed to varying extents yet mechanical testing revealed tissue development supported increased load bearing over time. Conclusions: Results clearly demonstrate the potential of a scaffold-first strategy in engineering viable autologous ACL tissue that may serve over the patient’s life time. The SeriACL graft supported autologous development of a mechanically robust, biologically viable ligament which stabilized the joint over a 12 mo period. Mechanical, clinical and histological results indicated the safety of the SeriACL with initial indications of efficacy. Thus, the implant may offer the potential of an ACL replacement graft without the deleterious side-effects associated with donor-site morbidity and allogenic and xenogenic grafts


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 257 - 257
1 Nov 2002
Parmar P Johnson D
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Purpose: To document healing of the anterior cruciate ligament. Introduction: Conventional wisdom holds that the anterior cruciate ligament (ACL) does not heal. In an athlete the ACL deficient knee is likely to be symptomatic and lead to functional instability. This has led to the belief that all ACL tears in the active athlete require reconstruction. Some ACL tears in recreational athletes are successfully treated conservatively with activity modification and bracing. A literature search was performed which found three articles on ACL healing. These articles felt that complete ACL tears could heal if patients were properly braced and rehabilitated. Materials and Methods: At the Carleton University Sports Medicine Clinic we retrospectively reviewed ACL tears diagnosed by the Lachman, pivot shift, and KT-1000 arthrometer testing. We then examined those whose clinical exam became stable by the same three tests. The latest follow up exam was performed by the same examiner (P.P). At the follow up exam, knee function was evaluated with the expanded IKDC form. Results: Nine patients were found to be asymptomatic and stable after an initial diagnosis of an ACL tear. In follow up the Lachman test had a good endpoint, the pivot shift was normal and the KT – 1000 manual max was less than 3mm. The IKDC results showed 3/9 were grade A, 5/9 were grade B and 1/9 was grade C. The clinical implication: ACL tears should be treated initially conservatively since in a small percentage of patients, the ACL tear can heal