Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

Abstract

Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling) compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP) using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found). For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies) was assessed and outcome data were collected for meta-analysis (151 studies). Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0–100% scale. Implantation of acellular biomaterials significantly improved cartilage regeneration by 15.6% compared to non-treated empty defect controls. The addition of biologics to biomaterials significantly improved cartilage regeneration by 7.6% compared to control biomaterials. No significant differences were found between biomaterials from natural or synthetic origin or between scaffolds, hydrogels and blends. No noticeable differences were found in outcome between animal models. The risk of bias assessment indicated poor reporting for the majority of studies, impeding an assessment of the actual risk of bias. In conclusion, implantation of biomaterials in osteochondral defects improves cartilage regeneration compared to natural healing, which is further improved by the incorporation of biologics.

Stellenwert der matrixaugmentierten Knochenmarkstimulation in der Behandlung von Knorpelschäden des Kniegelenks: Konsensusempfehlungen der AG Klinische Geweberegeneration der DGOU

“…Da bei dieser Vorgehensweise durch die Ahlen, besonders an den Rändern der Perforationsstellen, durch räumliche Verdrängung knöcherne Ausziehungen entstehen und diese impaktiert werden können, besteht die Gefahr, dass die eröffneten Kanäle nach MFx durch freie Knochenfragmente wieder verstopft werden. [65]. Berücksichtigt wurden ausschließlich Fall-Kontroll-Studien, bei denen im Tiermodell die Ergebnisse nach Knochenmarkstimulation mit und ohne zusätzlichen Einsatz von zellfreien Biomaterialien anhand eines semiquantitativen histologischen Scoring-Systems verglichen wurden.…”

Terapias Celulares y Productos de Ingeniería de Tejidos para el Tratamiento de Lesiones Condrales de Rodilla

“…Las técnicas que estimulan el sangrado del hueso subcondral y con ello la presencia de células estromales de la médula, han funcionado en pacientes con lesiones pequeñas (Gudas et al, 2005); sin embargo, conducen a la formación de fribrocartílago. Los auto o aloinjertos de cartílago están limitados por la cantidad de tejido disponible para injerto y también reportan fallas terapéuticas debido a la poca integración del injerto (Reddy et al, 2007;Pot et al, 2016).…”

“…Las propiedades microestructurales, físicas y químicas de estas matrices acelulares (sin células), contribuyen a crear un microambiente adecuado para que células mesenquimales provenientes de la médula ósea se adhieran, proliferen, diferencien y recambien la matriz artificial por cartílago hialino (Hoemann et al, 2005;Kang et al, 2008;Erggelet et al, 2009;Kon et al, 2015). Tienen la ventaja de que se pueden aplicar en procedimientos mínimamente invasivos y en un solo paso quirúrgico; además, al no requerir cultivo celular son menos costosas, se puede disponer de ellas de forma inmediata y tienen menos restricciones regulatorias, Pot et al, 2016. Los procedimientos basados en ésta aproximación son conocidos como condrogénesis autóloga inducida por matriz (AMIC, por sus siglas en inglés), Volz et al, 2017. El enorme desarrollo de la ciencia de los materiales, ha permitido estudiar las propiedades de los soportes o matrices; así como, hacer modificaciones de éstas propiedades para aumentar su bioactividad (Tatara & Mikos, 2016).…”

Osteochondral repair using an acellular dermal matrix—pilot in vivo study in a rabbit osteochondral defect model

“…Although cross‐linked acellular cartilage matrices have been described for repair of chondral and osteochondral defects, translation to the clinic is problematic. A meta‐analysis on the utility of acellular biomaterials for cartilage repair of an osteochondral defect concluded that the presence of acellular biomaterials was better than empty defect …”

“…These reports highlight and reinforce the ability of the ADM to remodel to tissue at the site of implantation. The natural architectural complexity of the ECM is maintained in the ADM compared to the single component biomaterials …”