BMSCs with tissue-engineered scaffolds for large bone segmental defects. A systematic review

Critical-sized bone defects (CSBD) represent a significant clinical challenge, stimulating researchers to seek new methods for successful bone reconstruction. The aim of this systematic review is to assess whether bone marrow stem cells (BMSCs) combined with tissue-engineered scaffolds have demonstrated improved bone regeneration in the treatment of CSBD in large preclinical animal models. A search of electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) focused on in vivo large animal studies identified ten articles according to the following inclusion criteria: 1. in vivo large animal models with segmental bone defects; 2. treatment with tissue-engineered scaffolds combined with BMSCs; 3. the presence of a control group; 4. a minimum of a histological analysis outcome. ARRIVE guidelines were used for quality assessment and SYRCLE's risk of bias tool was used to define internal validity. The results demonstrated that tissue-engineered scaffolds, either from autografts or allografts, when combined with BMSCs provide improved bone mineralization and bone formation, including a critical role in the remodeling phase of bone healing. BMSCs-seeded scaffolds showed improved biomechanical properties and microarchitecture properties of the regenerated bone when compared to untreated and scaffold-alone groups. This review highlights the efficacy of tissue engineering strategies for the repair of extensive bone defects in pre-clinical large-animal models. In particular, the use of mesenchymal stem cells, combined with bio-scaffolds seems to be a successful method in comparison to cell-free scaffolds.