{Reference Type}: Journal Article {Title}: Diatom-guided bone healing via a hybrid natural scaffold. {Author}: Mohammadi M;Abbaszadeh S;Nosrati-Siahmazgi V;Akbari M;Rezaei S;Musaie K;Eskandari MR;Santos HA;Poursina N;Shahbazi MA; {Journal}: Heliyon {Volume}: 10 {Issue}: 4 {Year}: 2024 Feb 29 {Factor}: 3.776 {DOI}: 10.1016/j.heliyon.2024.e25878 {Abstract}: Bone tissue engineering (BTE) involves the design of three-dimensional (3D) scaffolds that aim to address current challenges of bone defect healing, such as limited donor availability, disease transmission risks, and the necessity for multiple invasive surgeries. Scaffolds can mimic natural bone structure to accelerate the mechanisms involved in the healing process. Herein, a crosslinked combination of biopolymers, including gelatin (GEL), chitosan (CS), and hyaluronic acid (HA), loaded with diatom (Di) and β-sitosterol (BS), is used to produce GCH-Di-S scaffold by freeze-drying method. The GCH scaffold possesses a uniform structure, is biodegradable and biocompatible, and exhibits high porosity and interconnected pores, all required for effective bone repair. The incorporation of Di within the scaffold contributes to the adjustment of porosity and degradation, as well as effectively enhancing the mechanical property and biomineralization. In vivo studies have confirmed the safety of the scaffold and its potential to stimulate the creation of new bone tissue. This is achieved by providing an osteoconductive platform for cell attachment, prompting calcification, and augmenting the proliferation of osteoblasts, which further contributes to angiogenesis and anti-inflammatory effects of BS.