Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Sep 18, 2016; 7(9): 592-603
Published online Sep 18, 2016. doi: 10.5312/wjo.v7.i9.592
Biologic agents for anterior cruciate ligament healing: A systematic review
Berardo Di Matteo, Markus Loibl, Luca Andriolo, Giuseppe Filardo, Johannes Zellner, Matthias Koch, Peter Angele
Berardo Di Matteo, Luca Andriolo, Giuseppe Filardo, I Orthopaedic and Traumatologic Clinic - Biomechanics and Technology Innovation Laboratory, Rizzoli Orthopaedic Institute, 40136 Bologna, Italy
Markus Loibl, Johannes Zellner, Matthias Koch, Peter Angele, Department of Trauma Surgery, University Regensburg Medical Centre, 93042 Regensburg, Germany
Peter Angele, Sporthopaedicum Regensburg, 93053 Regensburg, Germany
Author contributions: Di Matteo B, Andriolo L, Filardo G and Koch M were responsible for the literature research and for collecting the data and preparing the figures and tables included in the manuscript; Di Matteo B, Loibl M, Zellner J and Angele P wrote the paper; Loibl M and Angele P were responsible for the critical revision of the entire manuscript.
Conflict-of-interest statement: No conflict of interest to declare for the present paper.
Data sharing statement: All the source data used to perform the present systematic review are available from the corresponding author at berardo.dimatteo@gmail.com.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Berardo Di Matteo, MD, I Orthopaedic and Traumatologic Clinic - Biomechanics and Technology Innovation Laboratory, Rizzoli Orthopaedic Institute, Via Pupilli n. 1, 40136 Bologna, Italy. berardo.dimatteo@gmail.com
Telephone: +39-051-6366567 Fax: +39-051-583789
Received: April 20, 2016
Peer-review started: April 22, 2016
First decision: June 6, 2016
Revised: June 22, 2016
Accepted: July 14, 2016
Article in press: July 18, 2016
Published online: September 18, 2016
Processing time: 144 Days and 12.2 Hours
Abstract
AIM

To systematically review the currently available literature concerning the application of biologic agents such as platelet-rich plasma (PRP) and stem cells to promote anterior cruciate ligament (ACL) healing.

METHODS

A systematic review of the literature was performed on the use of biologic agents (i.e., PRP or stem cells) to favor ACL healing during reconstruction or repair. The following inclusion criteria for relevant articles were used: Clinical reports of any level of evidence, written in English language, on the use of PRP or stem cells during ACL reconstruction/repair. Exclusion criteria were articles written in other languages, reviews, or studies analyzing other applications of PRP/stem cells in knee surgery not related to promoting ACL healing.

RESULTS

The database search identified 394 records that were screened. A total of 23 studies were included in the final analysis: In one paper stem cells were applied for ACL healing, in one paper there was a concomitant application of PRP and stem cells, whereas in the remaining 21 papers PRP was used. Based on the ACL injury pattern, two papers investigated biologic agents in ACL partial tears whereas 21 papers in ACL reconstruction. Looking at the quality of the available literature, 17 out of 21 studies dealing with ACL reconstruction were randomized controlled trials. Both studies on ACL repair were case series.

CONCLUSION

There is a paucity of clinical trials investigating the role of stem cells in promoting ACL healing both in case of partial and complete tears. The role of PRP is still controversial and the only advantage emerging from the literature is related to a better graft maturation over time, without documenting beneficial effects in terms of clinical outcome, bone-graft integration and prevention of bony tunnel enlargement.

Keywords: Platelet-rich plasma; Growth factors; Stem cells; Anterior cruciate ligament reconstruction; Anterior cruciate ligament repair; Anterior cruciate ligament healing; Sports medicine; Regenerative medicine

Core tip: There has been a growing interest in the past years on regenerative approaches to stimulate healing of musculo-skeletal tissues. The present systematic review focuses on the clinical application of biologic agents [platelet-rich plasma (PRP) and stem cells] to favor anterior cruciate ligament healing during procedures of reconstruction or repair. We show that there is inconclusive evidence to support the use of biologic augmentations, also due to the paucity of trials currently available, especially concerning stem cells. Looking at PRP, positive findings in terms of promotion of graft maturation were documented, but no beneficial influence was observed in terms of clinical outcome, bone-graft integration and prevention of tunnel enlargement.