Ligamentization of Tendon Grafts Treated With an Endogenous Preparation Rich in Growth Factors: Gross Morphology and Histology
Abstract
Purpose: To investigate whether the application of a particular platelet‐rich plasma preparation rich in growth factors (PRGF) during anterior cruciate ligament (ACL) surgery gives a potential advantage for better tendon graft ligamentization. Methods: This study included 37 volunteers who underwent either conventional (control group, n = 15) or PRGF‐assisted (n = 22) ACL reconstruction with an autogenous hamstring and required second‐look arthroscopy to remove hardware or loose bodies, treat meniscal tears or plica syndrome, or resect cyclops lesions at 6 to 24 months after ACL surgery. The gross morphologies of the grafts were evaluated on second‐look arthroscopy by use of the full arthroscopic score (0 to 4 points) to evaluate graft thickness and apparent tension (0 to 2 points) plus synovial coverage (0 to 2 points). At the same time, biopsy specimens were harvested uniformly from the grafted tendons. In these specimens the histologic transformation of the tendon graft to ACL‐like tissue was evaluated by use of the Ligament Tissue Maturity Index, and a score to assess the progression of new connective tissue enveloping the graft was created by use of 3 criteria previously used to characterize changes during ligament healing: cellularity, vascularity, and collagen properties. Results: The overall arthroscopic evaluation of PRGF‐treated grafts showed an excellent rating in 57.1% of the knees (score of 4) and a fair rating in 42.9% (score of 2 or 3). In contrast, evaluation of untreated grafts showed an excellent rating in 33.3% of the knees, a fair rating in 46.7%, and a poor rating in 20% (score of 0 or 1). Overall, arthroscopic evaluations were not statistically different between PRGF and control groups ( P = .051). PRGF treatment influenced the histologic characteristics of the tendon graft, resulting in tissue that was more mature than in controls ( P = .024). Histologically evident newly formed connective tissue enveloping the graft was present in 77.3% of PRGF‐treated grafts and 40% of controls. The appearance of the connective tissue envelope changed with increasing time from surgery. On the basis of the histologic findings, we suggest that the remodeling of PRGF‐treated grafts involves the formation of synovial‐like tissue enveloping the graft. This tissue is eventually integrated in the remodeled tendon graft, conferring a similar appearance to the normal ACL. Conclusions: The use of PRGF influenced the histologic characteristics of tendon grafts, resulting in more remodeling compared with untreated grafts. We have shown temporal histologic changes during the 6‐ to 24‐month postoperative period of graft maturation, with newly formed connective tissue enveloping most grafts treated with PRGF. Level of Evidence: Level III, case‐control study.
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The influx of host fibroblasts into the necrotic area of the graft occurs early in the healing phase, followed by remodeling of the tendon graft.
“The influx of host fibroblasts into the necrotic area of the graft reportedly occurs early in the healing phase, followed by remodeling of the tendon graft.”
A tendon graft implanted during anterior cruciate ligament reconstruction undergoes a maturation process known as ligamentization.
“A tendon graft implanted during ACLR undergoes a maturation process known as ligamentization [9, 10].”
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.
“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].”
Cites
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Remodelling of human hamstring autografts after anterior cruciate ligament reconstruction
Janssen, R. P. A., van der Wijk, J., Fiedler, A., Schmidt, T., Sala, H. A. G. M., & Scheffler, S. U. (2011) · Knee Surgery, Sports Traumatology, Arthroscopy · doi:10.1007/s00167-011-1419-y · Cited by 109 · see citing works
Cook, J. L., Smith, P. A., Bozynski, C. C., Kuroki, K., Cook, C. R., Stoker, A. M., & Pfeiffer, F. M. (2016) · Journal of Orthopaedic Research · doi:10.1002/jor.23054 · Cited by 91 · see citing works
Autologous Platelet-Rich Plasma: A Revolution in Soft Tissue Sports Injury Management?
Mei-Dan, O., Lippi, G., Sánchez, M., Andia, I., & Maffulli, N. (2010) · The Physician and Sportsmedicine · doi:10.3810/psm.2010.12.1835 · Cited by 83 · see citing works
Self-citationYoshioka, T., Kanamori, A., Washio, T., Aoto, K., Uemura, K., Sakane, M., & Ochiai, N. (2013) · Knee Surgery, Sports Traumatology, Arthroscopy · doi:10.1007/s00167-012-2002-x · Cited by 61 · see citing works
Park, J., Jo, S., Lee, M.-K., Kim, T.-H., Sung, I.-H., & Lee, J. K. (2022) · Bone & Joint Research · doi:10.1302/2046-3758.1111.bjr-2021-0548.r2 · Cited by 12 · see citing works
Park, J., Soh, H., Jang, Y.-K., Lee, Y. S., Lee, M.-K., Kim, H., Kim, T.-H., Alkhelaifi, K., Kim, T.-J., & Lee, J. K. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04760-1 · Cited by 3 · see citing works
- Authors
- Sánchez, M., Anitua, E., Azofra, J., Prado, R., Muruzabal, F., & Andia, I.
- Affiliations
- Unidad de Cirugía Artroscópica (ES)
- BTI Biotechnology Institute (ES)
- BTI Biotechnology Institute IMASD Vitoria‐Gasteiz Spain
- Venue
- Arthroscopy
- Publisher
- Wiley
- Published
- 2010-01-18
- Volume
- 26
- Issue
- 4
- Pages
- 470-480
- ISSN
- 0749-8063 (ISSN-L)
- 1526-3231
- OpenAlex
- W2143110295
- Cited by
- 235
- References
- 1
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 3 · 2023: 8 · 2022: 11 · 2021: 23 · 2020: 14 · 2019: 15 · 2018: 16 · 2017: 15 · 2016: 13 · 2015: 23 · 2014: 22 · 2013: 18 · 2012: 22
- FWCI
- 19.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Arthroscopy The Journal of Arthroscopic and Related Surgery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Knee injuries and reconstruction techniques
- Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Tendon Structure and Treatment
- Keywords
- platelet-rich growth factor, anterior cruciate ligament reconstruction, hamstring tendon graft, graft remodeling, graft histology, second-look arthroscopy, growth factors, connective tissue formation, collagen properties, vascularity, cellularity, graft integration, Cyclops
- MeSH terms
- Adolescent, Adult, Arthroscopy, Female, Humans, Knee Joint, Male, Middle Aged, Tendons, Anterior Cruciate Ligament, Intercellular Signaling Peptides and Proteins, Platelet-Rich Plasma, Young Adult
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