Biologic agents for anterior cruciate ligament healing: A systematic review

Abstract

AIMTo 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.METHODSA 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.RESULTSThe 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.CONCLUSIONThere 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.

Arthroscopic Harvesting of Autologous Bone Graft for Use as a Mesenchymal Stem Cell Carrier in Anterior Cruciate Ligament Reconstruction

“…8 Various growth factors, such as transforming growth factor-b (TGF-b), are also present in bones. 13,14 A study examining the injection of upregulating TGF-b MSCs into osseous tunnels during rabbit ACLRs found tighter entheses, reduced scar tissue, sealed bone tunnels, and greater quantities of cell types indicative of healing compared with controls. 6 Moreover, they found that overexpression of TGF-b promoted greater maximum load, rigidity, new bone formation, and mineral densitydwhich are integral to achieving robust graft fixation.…”

Editorial Commentary: Bone Tunnel Grafting for Two-Stage Anterior Cruciate Ligament Revision and the Meaning of Life for an Arthroscopic Surgeon

“…Another option is the selection of a bone allograft, yet the stringent regulations and the limited availability of allograft tissue are well known in many countries around the world, not to mention the high financial costs associated with the harvesting and preservation of bony specimens. 2 In recent decades, there has been a growing interest in the development of "biologic" strategies to improve the outcomes of musculoskeletal surgery 3,4 : bony substitutes have been increasingly adopted in clinical practice in a wide range of conditions. 5 Humanitas University (E.K.)…”

Outcomes of Anterior Cruciate Ligament Reconstruction Using Biologic Augmentation in Patients 21 Years of Age and Younger

“…The use of biologic agents, such as platelet-derived growth factors and stem cells, remains an area of interest as surgeons explore new means to improve healing. 7 Platelet-rich plasma (PRP) is a biologic agent that has received significant attention. Although it is known that patients may show differing levels of platelets, often varying by time of day, all patients experience up to a 4-fold increase in platelet concentration with appropriate processing.…”