Muscle-Secreted Factors Improve Anterior Cruciate Ligament Graft Healing: An<i>In Vitro</i>and<i>In Vivo</i>Analysis

Ghebes, Corina Adriana; Gröen, Nathalie; Cheuk, Yau-Chuk; Fu, Sai‐Chuen; Fernandes, Hugo; Saris, Daniël B.F.

doi:10.1089/ten.tea.2016.0546

Cited by 14 publications

(11 citation statements)

References 48 publications

(49 reference statements)

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“…Myoblast conditioned medium (Myo-CM) was also reported to upregulate tendon/ligament genes, TNMD, tenascin C and COMP, and enhanced collagen production in vitro. When tested on rats for ACL reconstruction, Myo-CM accelerated femoral tunnel closure but not tibial tunnel closure [145]. Physiologically, tenocytes synthesize the ECM including collagen and other proteins for tendon formation [146].…”

Section: Secretomes/growth Factorsmentioning

confidence: 99%

Current Progress in Tendon and Ligament Tissue Engineering

Lim

Liau

et al. 2019

Tissue Eng Regen Med

153

146

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BACKGROUND: Tendon and ligament injuries accounted for 30% of all musculoskeletal consultations with 4 million new incidences worldwide each year and thus imposed a significant burden to the society and the economy. Damaged tendon and ligament can severely affect the normal body movement and might lead to many complications if not treated promptly and adequately. Current conventional treatment through surgical repair and tissue graft are ineffective with a high rate of recurrence. METHODS: In this review, we first discussed the anatomy, physiology and pathophysiology of tendon and ligament injuries and its current treatment. Secondly, we explored the current role of tendon and ligament tissue engineering, describing its recent advances. After that, we also described stem cell and cell secreted product approaches in tendon and ligament injuries. Lastly, we examined the role of the bioreactor and mechanical loading in in vitro maturation of engineered tendon and ligament. RESULTS: Tissue engineering offers various alternative ways of treatment from biological tissue constructs to stem cell therapy and cell secreted products. Bioreactor with mechanical stimulation is instrumental in preparing mature engineered tendon and ligament substitutes in vitro. CONCLUSIONS: Tissue engineering showed great promise in replacing the damaged tendon and ligament. However, more study is needed to develop ideal engineered tendon and ligament.

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Section: Secretomes/growth Factorsmentioning

confidence: 99%

Current Progress in Tendon and Ligament Tissue Engineering

Lim

Liau

et al. 2019

Tissue Eng Regen Med

153

146

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“…Tendon depends on its adherent musculature for development. 4 The biological potential of the remnant musculature to help the healing of the tendon graft has already been elucidated by Ghebes et al 10 The muscle tissue contains neurotrophic factors that assist in the survival and growth of proprioceptive neurons. 8 Skeletal muscle tissue also has a regulatory effect on tendon development through the paracrine secretion of key factors related to tendon development.…”

Section: Discussionmentioning

confidence: 99%

“…It is worth mentioning that the same types of cells in native ACL fragments were found in the ACL remnants from patients who underwent surgery ( Figure 5). .002 Femoral portion 9.32 ± 0.93 (9-11) 8.31 ± 0.97 (7)(8)(9)(10) <.001 Tibial portion 9.51 ± 0.76 (8-11) 8.40 ± 1.04 (7)(8)(9)(10) .004…”

Section: Histological Analysismentioning

confidence: 99%

Remnant Muscle Preservation on Hamstring Tendon Autograft During ACL Reconstruction Promotes Volumetric Increase With Biological and Regenerative Potential

Funchal¹,

Ortiz²,

Jimenez

et al. 2021

Orthopaedic Journal of Sports Medicine

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Background: The removal of all adherent muscle tissue from the hamstring graft during anterior cruciate ligament reconstruction (ACLR) is common practice. However, there is a paucity of research to justify this removal or evaluate its biological implications. Purpose/Hypothesis: The purpose of this study was to (1) evaluate the histological characteristics of the myotendinous muscle tissue harvested from hamstring tendons, (2) compare the final diameter of the prepared graft before and after the removal of the remnant musculature, and (3) evaluate patients who were treated with and without preservation of the graft-adhered muscle. The hypothesis was that the adherent musculature of the graft would have cells that could contribute to graft incorporation and revascularization, assist in the proprioceptive capacity of the neoligament, and increase the graft’s diameter. Study Design: Cohort study; Level of evidence, 3. Methods: We divided 84 patients into 2 groups: group 1 underwent ACLR using hamstring tendon autograft with adherent musculature, and group 2 underwent ACLR using hamstring tendon autograft stripped of its remnant muscle. All patients had minimum 2-year follow-up. The muscle harvested from the graft in group 2 was submitted for histological examination, and the graft diameter before and after muscle removal was compared. The Tegner activity scale and Lysholm scores were determined preoperatively and at 12 and 24 months postoperatively. Results: There was a significant difference in graft diameter between groups. The evaluation of the graft diameter in group 2 showed a decrease of 11.52% after removal of muscle tissue from the tendon graft. Patients from group 1 had better Tegner and Lysholm scores (mean ± SD) after 12 months (Tegner, 8.03 vs 7 [ P = .004]; Lysholm, 95.48 ± 1.2 vs 87.54 ± 3.21 [ P = .002]) and better Lysholm scores after 24 months (95.76 ± 2.1 vs 89.32 ± 2.47; P = .002). The muscle tissue of the analyzed fragments presented a pattern with fibrous tissue beams, invaginating regularly and sequentially from the myotendinous junction into the muscles. Conclusion: Preserving the muscle tissue on tendon grafts promoted a volumetric increase in the final autograft diameter and demonstrated biological and regenerative potential. Patients who underwent ACLR using the tendon with the muscle attached had better functional scores at 2-year follow-up as compared with patients treated using the tendon with the muscle removed.

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“…In an in vitro experiment conducted by Ghebes et al, co-culturing myoblasts with hamstring tendon-derived cells upregulated the expression of tendon/ligament differentiation markers and increased the synthesis of collagen units [41]. Moreover, authors analyzed the influence of muscle-secreted factors on the ACL reconstruction in the rat model.…”

Section: Preservation Of Muscle Tissue On Tendon Graftmentioning

confidence: 99%

Maturation of Anterior Cruciate Ligament Graft—Possibilities of Surgical Enhancement: What Do We Know So Far?

Ebisz¹,

Góralczyk

Mostowy

et al. 2021

Applied Sciences

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The purpose of this study is to review the surgical methods of enhancing anterior cruciate ligament (ACL) graft maturation. Several methods of ACL maturation enhancement were identified through research of the literature available in the PubMed database. ACL remnant preservation was the most extensively investigated technique. ACL reconstruction with a pedunculated hamstring graft provides superior revascularization of the graft along with higher mechanical strength. The usage of a graft enveloped with a periosteum was proposed to enhance the tendon-bone unit formation, and consequently, to prevent the bone tunnel widening. The muscle tissue on the graft is a potential source of stem cells. However, an excessive amount may weaken whole graft strength despite its enhanced remodeling. Similarly, amniotic tissue may augment the ACL reconstruction with stem cells and growth factors. Despite the existence of several surgical techniques that utilize amnion, the outcomes of these augmentation methods are lacking. Lastly, the intra-articular transplantation of the synovium on the surface of an ACL was proposed to augment the graft with synovial tissue and blood vessels. In conclusion, diverse approaches are being developed in order to enhance the maturation of an ACL reconstruction graft. Although these approaches have their foundation in on well-established scientific research, their outcomes are still equivocal. Clinical trials of high quality are needed to evaluate their utility in clinical practice.

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Muscle-Secreted Factors Improve Anterior Cruciate Ligament Graft Healing: AnIn VitroandIn VivoAnalysis

Cited by 14 publications

References 48 publications

Current Progress in Tendon and Ligament Tissue Engineering

Current Progress in Tendon and Ligament Tissue Engineering

Remnant Muscle Preservation on Hamstring Tendon Autograft During ACL Reconstruction Promotes Volumetric Increase With Biological and Regenerative Potential

Maturation of Anterior Cruciate Ligament Graft—Possibilities of Surgical Enhancement: What Do We Know So Far?

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