The Role of Three-Dimensional Scaffolds in Treating Long Bone Defects: Evidence from Preclinical and Clinical Literature—A Systematic Review

Abstract

Long bone defects represent a clinical challenge. Bone tissue engineering (BTE) has been developed to overcome problems associated with conventional methods. The aim of this study was to assess the BTE strategies available in preclinical and clinical settings and the current evidence supporting this approach. A systematic literature screening was performed on PubMed database, searching for both preclinical (only on large animals) and clinical studies. The following string was used: “(Scaffold OR Implant) AND (Long bone defect OR segmental bone defect OR large bone defect OR bone loss defect).” The search retrieved a total of 1573 articles: 51 preclinical and 4 clinical studies were included. The great amount of preclinical papers published over the past few years showed promising findings in terms of radiological and histological evidence. Unfortunately, this in vivo situation is not reflected by a corresponding clinical impact, with few published papers, highly heterogeneous and with small patient populations. Several aspects should be further investigated to translate positive preclinical findings into clinical protocols: the identification of the best biomaterial, with both biological and biomechanical suitable properties, and the selection of the best choice between cells, GFs, or their combination through standardized models to be validated by randomized trials.

Scaffolds and coatings for bone regeneration

“…Tissue engineering paradigm has several components: a scaffold that mimics the tissue that needs to be regenerated; cells to lay down the ECM; morphogenic signs so cells can differentiate. Tissue engineering can be applied to all types of tissues that constitutes human body such as bone tissue [35,36], osteochondral [37,38], cartilage [39,40], neural tissue [41,42]; skeletal tissue [43,44]; skin [45,46]; meniscus [47,48]; or even blood vessels [49]. Bone tissue engineering strategies aim to achieve bone regeneration which is required in several clinical conditions including but not limited to osteoporosis [15,50], bone infection [15] and resection of musculoskeletal sarcoma which usually results in large bone defects [51].…”

Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair

“…Bone tissue engineering generally starts with the in vitro culturing of BMSC cells with high osteogenic differentiation potential alone or in the presence of scaffold carriers to develop and manipulate a tissue-engineered construct followed by implanting into the defected site to augment bone repair [104]. Despite bone tissue engineering possess the advantages that the same mechanical and functional properties and superior integration to the host bone tissue and has already acquired some better satisfactions in the clinical treatment of bone defect [105-108], the extended clinical application is hampered by major limitations, such as the poor availability and the time required to differentiate up to a stage suitable for implantation of the BMSCs, the inflammatory environment of implanted site triggered by the bone defect itself and the surgical procedure and the further new bone tissue and surrounding host tissue degeneration after construct implantation [21, 109, 110]. Therefore, the improvement of the present available technologies is still needed to acquire more satisfactory clinical outcomes in bone defect repair.…”

Scaffolds as Structural Tools for Bone-Targeted Drug Delivery

“…The treatment requires curettage of the area and infusion of bone marrow derived stem cells [ 128 , 129 ]. The use of bone scaffold is a novel treatment under investigation [ 130 ]. We envision as one of the future targets of scaffolds loaded with osteogenic factors, antibiotics and/or mesenchymal stem cells delivery in the fracture area during the primary surgical treatment in order to decrease the complications rate.…”