Remodelling of human hamstring autografts after anterior cruciate ligament reconstruction
Open accessAbstract
Purpose: Histological analysis of the remodelling process of human hamstring tendon (HT) grafts after standardized anterior cruciate ligament reconstruction (ACLR) with an accelerated rehabilitation protocol. Methods: Sixty‐seven patients underwent retrieval of mid‐substance biopsies after clinically successful hamstring autograft ACLR. Samples were allocated to one of three groups depending on the time point of retrieval: group 1 (6–12 months; n = 15), group 2 (13–24 months; n = 16) and group 3 (>24 months; n = 11). Biopsies from native HT (n = 17) and ACL (n = 8) served as controls. Cellular density, vascular density and myofibroblast density and collagen fibril alignment were analysed by haematoxylin–eosin, Masson‐Goldner‐Trichrom and immunohistochemical staining protocols. Results: Compared with native HT (330.4/mm²), total cell number was increased in groups 1‐3 (Group 1 = 482.0/mm² (P = 0.036); group 2 = 850.9/mm² (P = 0.005); and group 3 = 595.6/mm² (P = 0.043). There were no significant differences between the groups for vessel density. Myofibroblast density was higher in group 2 (199.6/mm²) compared with native HT (1.9/mm², P = 0.014). Collagen orientation was irregular up to 12 months. Thereafter, collagen orientation became more regular, adapting to, but not fully restoring, the appearance of the intact ACL. For the first 12 months, cells were predominantly ovoid. Ensuing cell morphology changed to spindle shaped in group 2 and predominantly narrow long cells over 24 months. Conclusion: Human hamstring grafts showed typical stages of graft remodelling, which was not complete up to 2 years after ACLR. The remodelling process in humans was prolonged compared with the results obtained in several animal studies. Level of evidence: Case–control study, Level III.
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The heterogeneous composition of collagen fibers of varying diameters of native anterior cruciate ligament is never restored after anterior cruciate ligament reconstruction.
“However, the predominant synthesis of type III collagen, which is typically found in weaker scar tissue, continues at higher concentrations, and the heterogeneous composition of collagen fibers of varying diameters of native ACL is never restored [5, 11, 12].”
From A new biological enhancement therapy for anterior cruciate ligament reconstruction: the preclinical proof of anterior cruciate ligament reconstruction with tendon graft reseeded with autologous anterior cruciate ligament-derived cells (2025) · cites this paper as [5]
The Discussion reports that a cited study of patellar-tendon grafts did not find the native ACL’s mean collagen-fibril diameter or bimodality restored during a transformation period of up to two years. This paper’s own Results concern collagen orientation, not fibril diameters, and neither finding establishes that the native diameter distribution is never restored after reconstruction. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe mechanical properties of an implanted graft, regardless of graft type, do not return to normal after anterior cruciate ligament reconstruction surgery.
“However, the mechanical properties of the implanted graft, regardless of graft type, do not return to normal after ACLR surgery [3–5].”
From A new biological enhancement therapy for anterior cruciate ligament reconstruction: the preclinical proof of anterior cruciate ligament reconstruction with tendon graft reseeded with autologous anterior cruciate ligament-derived cells (2025) · cites this paper as [5]
The Discussion reports that animal grafts did not fully regain the mechanical strength of an intact ACL, reaching only 50–60% of its failure strength. But this does not establish that mechanical properties never return to normal in humans or regardless of graft type; the paper’s own conclusion concerns incomplete remodelling of human hamstring grafts up to two years after reconstruction. (LLM, conf=0.86)
Experimental — accuracy not yet measuredJanssen et al. reported a substantial increase in myofibroblast and vessel density up to 24 months, confirming that collagen composition and orientation did not return to normal in the study period.
“Janssen et al., in their retrieval biopsy studies of 67 human ACL grafts, reported a substantial increase in myofibroblast and vessel density up to 24 months, confirming that collagen composition and orientation did not return to normal in the study period [5].”
From A new biological enhancement therapy for anterior cruciate ligament reconstruction: the preclinical proof of anterior cruciate ligament reconstruction with tendon graft reseeded with autologous anterior cruciate ligament-derived cells (2025) · cites this paper as [5]
The Methods report 67 patients, but only 42 graft biopsies; the remaining 25 biopsies were controls. The Results and Discussion report increased myofibroblast and vessel density through 13–24 months and collagen orientation that did not return to normal during the study. They do not establish that collagen composition failed to return to normal; myofibroblast density also declined after 24 months, and vessel-density differences between groups were not significant. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSeveral human biopsy studies have confirmed a similar remodeling cascade of graft necrosis (although to a smaller extent), recellularization, revascularization, and changes in collagen composition during the healing of the tendon graft.
“However, several human biopsy studies have confirmed a similar remodeling cascade of graft necrosis (although to a smaller extent), recellularization, revascularization, and changes in collagen composition during the healing of the tendon graft [5, 9, 10, 66].”
The predominant synthesis of type III collagen, which is typically found in weaker scar tissue, continues at higher concentrations after anterior cruciate ligament reconstruction.
“However, the predominant synthesis of type III collagen, which is typically found in weaker scar tissue, continues at higher concentrations, and the heterogeneous composition of collagen fibers of varying diameters of native ACL is never restored [5, 11, 12].”
From A new biological enhancement therapy for anterior cruciate ligament reconstruction: the preclinical proof of anterior cruciate ligament reconstruction with tendon graft reseeded with autologous anterior cruciate ligament-derived cells (2025) · cites this paper as [5]
The Results report irregular collagen orientation after ACL reconstruction, but do not identify collagen types or measure their synthesis or concentration. A search for type III collagen found it only in a cited paper’s title in the References; our copy does not address whether type III collagen remains predominant or is associated with weaker scar tissue. (LLM, conf=0.76)
Experimental — accuracy not yet measured
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- Authors
- Janssen, R. P. A., van der Wijk, J., Fiedler, A., Schmidt, T., Sala, H. A. G. M., & Scheffler, S. U.
- Affiliations
- Máxima Medisch Centrum (NL)
- <!--<label>1</label>--> Orthopaedic Center Máxima Máxima Medical Center Postbus 90052 5600 PD Eindhoven The Netherlands
- Stiftung Charité (DE)
- Corresponding author
- Janssen, Rob P. A.
- Venue
- Knee Surgery, Sports Traumatology, Arthroscopy
- Publisher
- Wiley
- Published
- 2011-02-04
- Volume
- 19
- Issue
- 8
- Pages
- 1299-1306
- ISSN
- 0942-2056 (ISSN-L)
- 1433-7347
- PMC
- PMC3136699
- OpenAlex
- W2012892026
- Cited by
- 109
- References
- 34
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 9 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 10 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 4 · 2014: 5 · 2013: 8 · 2012: 7
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Knee Surgery Sports Traumatology Arthroscopy (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Knee injuries and reconstruction techniques
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Keywords
- anterior cruciate ligament reconstruction, hamstring tendon graft, graft remodeling, accelerated rehabilitation, myofibroblasts, collagen fibril alignment, cell density, vessel density, graft histology, graft maturation
- MeSH terms
- Adult, Biopsy, Needle, Female, Follow-Up Studies, Humans, Immunohistochemistry, Knee Injuries, Male, Middle Aged, Regeneration, Retrospective Studies, Tendons, Thigh, Time Factors, Transplantation, Autologous, Cohort Studies, Chi-Square Distribution, Statistics, Nonparametric, Young Adult, Anterior Cruciate Ligament Reconstruction
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