Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies

Abstract

Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP) were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies). Cartilage regeneration was expressed on an absolute 0–100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

Ultrapurified Alginate Gel Containing Bone Marrow Aspirate Concentrate Enhances Cartilage and Bone Regeneration on Osteochondral Defects in a Rabbit Model

“…22 A previous systematic review found that cellular biomaterials significantly improve cartilage regeneration by 18.6% compared with acellular biomaterials. 23 Based on these reports, the implantation of UPAL gel would need to be combined with cell transplantation to treat large osteochondral defects.…”

Autologous stem cell-derived chondrocyte implantation with bio-targeted microspheres for the treatment of osteochondral defects

“…Also, it is stated that addition of the cell, as an important component of tissue engineering, leads to healing by production of many bioactive components [42]. A meta-analysis including 117 studies by Pot et al indicated that although results varied between different cell sources, the results of the applications including cells were superior to application without cells [43]. As also stated by an important author of autologous chondrocyte implantation Brittberg, cells are always necessary to repair a damaged tissue in terms of biology [44].…”

Dynamic Compressive Loading Improves Cartilage Repair in an In Vitro Model of Microfracture: Comparison of 2 Mechanical Loading Regimens on Simulated Microfracture Based on Fibrin Gel Scaffolds Encapsulating Connective Tissue Progenitor Cells

“…34 Microfracture is a minimally invasive and inexpensive 1-step approach. 38 It consists of the targeted disruption of the subchondral bone to form a clot rich in intramedullary mesenchymal stem or marrow stromal cells (MSCs) 33,45 that fills the defect. Over time, the MSCs generate a fibrocartilaginous tissue that integrates with the surrounding hyaline cartilage.…”