Effect of chitosan/inorganic nanomaterial scaffolds on bone regeneration and related influencing factors in animal models: A systematic review

Abstract

Bone tissue engineering (BTE) provides a promising alternative for transplanting. Due to biocompatibility and biodegradability, chitosan-based scaffolds have been extensively studied. In recent years, many inorganic nanomaterials have been utilized to modify the performance of chitosan-based materials. In order to ascertain the impact of chitosan/inorganic nanomaterial scaffolds on bone regeneration and related key factors, this study presents a systematic comparison of various scaffolds in the calvarial critical-sized defect (CSD) model. A total of four electronic databases were searched without publication date or language restrictions up to April 2022. The Animal Research Reporting of In Vivo Experiments 2.0 guidelines (ARRIVE 2.0) were used to assess the quality of the included studies. Moreover, the risk of bias (RoB) was evaluated via the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool. After the screening, 22 studies were selected. None of these studies achieved high quality or had a low RoB. In the available studies, scaffolds reconstructed bone defects in radically different extensions. Several significant factors were identified, including baseline characteristics, physicochemical properties of scaffolds, surgery details, and scanning or reconstruction parameters of micro-computed tomography (micro-CT). Further studies should focus on not only improving the osteogenic performance of the scaffolds but also increasing the credibility of studies through rigorous experimental design and normative reports.

Keywords: animal models; bone regeneration; calvarial bone defects; chitosan; inorganic nanomaterials.

FIGURE 1

Schematic diagram of the scoring system.

FIGURE 2

Flow chart of studies selected for the systematic review.

FIGURE 3

Results of the quality assessment of 22 studies applying ARRIVE 2.0 guidelines. The bar graph shows the percentage frequencies of 21 items. It is to be noted that the former 10 items belong to the essential set, whereas the latter 11 are in the recommendation set.

FIGURE 4

Results of the evaluation bias risk of 22 included studies applying SYRCLE’s RoB tool. The bar graph shows the percentage frequencies of 10 sources of bias. It is to be noted that the main sources of bias are “incomplete outcome data” and “selective outcome reporting.”

FIGURE 5

Summary of the key factors that influence the effects of chitosan/inorganic nanomaterial scaffolds on osteogenesis in calvaria CSD models. DD, the degree of deacetylation; MW, molecular weight.

FIGURE 6

Schematic diagram for the mechanism of cell adhesion on scaffolds. Integrin, located on the cell membrane, is consisted of an a-subunit and a ß-subunit, which mediates cell adhesion to the extracellular matrix via binding to the RGD sequences in some proteins, such as collagen, fibronectin, vitronectin, and laminin.