Tissue engineering and regenerative medicine strategies in meniscus lesions.
OBJECTIVE
The aim of this systematic review was to address tissue engineering and regenerative medicine (TERM) strategies applied to the meniscus, specifically (1) clinical applications, indications, results, and pitfalls and (2) the main trends in research assessed by evaluation of preclinical (in vivo) studies.


METHODS
Three independent reviewers performed a search on PubMed, from 2006 to March 31, 2011, using the term "meniscus" with all of the following terms: "scaffolds," "constructs," "cells," "growth factors," "implant," "tissue engineering," and "regenerative medicine." Inclusion criteria were English language-written, original clinical research (Level of Evidence I to IV) and preclinical studies of TERM application in knee meniscal lesions. Reference lists and related articles on journal Web sites of selected articles were checked until prepublication for potential studies that could not be identified eventually by our original search. The modified Coleman Methodology score was used for study quality analysis of clinical trials.


RESULTS
The PubMed search identified 286 articles (a similar search from 2000 to 2005 identified 161 articles). Non-English-language articles (n = 9), Level V publications (n = 19), in vitro studies (n = 118), and 102 studies not related to the topic were excluded. One reference was identified outside of PubMed. Thirty-eight references that met the inclusion criteria were identified from the original search. On the basis of our prepublication search, 2 other references were included. A total of 9 clinical and 31 preclinical studies were selected for further analysis. Of the clinical trials, 1 was classified as Level I, 2 as Level II, and 6 as Level IV. Eight referred to acellular scaffold implantation for partial meniscal replacement, and one comprised fibrin clot application. The mean modified Coleman Methodology score was 48.0 (SD, 15.7). Of the preclinical studies, 11 original works reported on studies using large animal models whereas 20 research studies used small animals. In these studies the experimental design favored cell-seeded scaffolds or scaffolds enhanced with growth factors (GFs) in attempts to improve tissue healing, as opposed to the plain acellular scaffolds that were predominant in clinical trials. Injection of mesenchymal stem cells and gene therapy are also presented as alternative strategies.


CONCLUSIONS
Partial meniscal substitution using acellular scaffolds in selected patients with irreparable loss of tissue may be a safe and promising procedure. However, there is only 1 randomized controlled study supporting its application, and globally, many methodologic issues of published trials limit further conclusions. We registered a different trend in preclinical trials, with most considering augmentation of scaffolds by cells and/or GFs, as opposed to the predominantly acellular approach in clinical trials. Different TERM approaches to enhance meniscal repair or regeneration are in preclinical analysis, such as the use of mesenchymal stem cells, gene therapy, and GFs alone or in combination, and thus could be considered in the design of subsequent trials.


METHODS
Level IV, systematic review of Level I to IV studies.
3B's Research Group-Biomaterials, Biodegradables and Biomimetics, Minho University, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal. heldermdpereira@gmail.com
Hélder
H
Pereira
Ana M
AM
Frias
Joaquim Miguel
JM
Oliveira
João
J
Espregueira-Mendes
Rui Luís
RL
Reis
D006801:Humans; D007718:Knee Injuries / Q000503:physiopathology / Q000601:surgery*; D008592:Menisci, Tibial / Q000601:surgery*; D017410:Practice Guidelines as Topic; D020127:Recovery of Function / Q000502:physiology*; D044968:Regenerative Medicine / Q000592:standards*; D000070600:Tibial Meniscus Injuries; D023822:Tissue Engineering / Q000592:standards*