FULL PAPER 1700539 (1 of 12) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mme-journal.de The Tunable Porous Structure of Gelatin–Bioglass Nanocomposite Scaffolds for Bone Tissue Engineering Applications: Physicochemical, Mechanical, and In Vitro Properties Neda Arabi, Ali Zamanian,* Sarvenaz N. Rashvand, and Farnaz Ghorbani N. Arabi, Dr. A. Zamanian, F. Ghorbani Biomaterials Research Group Nanotechnology and Advanced Materials Department Materials and Energy Research Center (MERC) Tehran 3177983634, Iran E-mail: a-zamanian@merc.ac.ir S. N. Rashvand Department of Bioengineering College of Engineering Temple University Philadelphia, 19122 PA, USA S. N. Rashvand Children’s Hospital of Philadelphia Philadelphia 19104 PA, USA F. Ghorbani Department of Biomedical Engineering Tehran Science and Research Branch Islamic Azad University Tehran 1477893855, Iran The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/mame.201700539. DOI: 10.1002/mame.201700539 1. Introduction Tissue engineering is a promising approach for various tissue or organs regeneration such as bone, [1] nerve, [2] cardiovascular, [3] etc. In bone regeneration research, scaffolds can be incorporated with/without appropriate cells such as stem cells or osteoblasts and growth factors like Bone morphogenetic proteins-2 (BMP-2) to support new bone for- mation. [4,5] Biocompatibility and intercon- nected porous microstructure of scaffolds are critical factors to facilitate the cellular proliferation, migration, and successful regeneration. Synthetic scaffolds promote healing process by mimicking the original extra cellular matrix (ECM), supplying sub- strate for cellular adhesion, stimulating osteogenesis and providing a template with required physicochemical and mechanical properties, sterilizability, etc. [6] One of the significant challenges in biomedical research is selecting the appropriate material for a particular application so that the chemistry, sur- face energy, shape, microstructure, and mechanical characteristics resemble the target tissue. [7] Polymers are one of the most common materials that have been used for fabrication of tissue engineering scaf- folds. Natural polymers (collagen, [8] gelatin, [9] chitosan, [10] etc.) have shown more similarity to the composition of the body following better interaction with cells. [11] Among mentioned materials, gelatin has gained a lot of attention due to its biocom- patibility, hydrophilic nature, and biodegradable behavior. [12] However, gelatin has not been able to provide the required mechanical properties for bone tissue engineering applica- tions. To overcome this issue, bioceramics with high corro- sion and compression resistance can be added to gelatin. The same results have been observed by Nagarajan et al. [13,14] They added boron nitride and graphene oxide to electrospun gelatin nanofibers separately, which then led to improved mechanical strength and scaffold–tissue interactions. The ability of bio- active ceramics, such as hydroxyapatite (HAP), [15] calcium phos- phate, [16] and bioactive glasses (BG) [17] to react with physiological fluids also resulted in the formation of mineralized layers and superior regeneration of bone defects. [18] BG has proven to be a Nanocomposite Scaffolds Unidirectional freeze-casting method is used to fabricate gelatin–bioglass nano- particles (BGNPs) scaffolds. Transmission electron microscopy (TEM) images show that sol–gel prepared BGNPs are distributed throughout the scaffold with diameters of less than 10 nm. Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetric are used to evaluate the physicochemical properties of BGNPs. Scanning electron microscopy (SEM) micrographs pre- sent an oriented porous structure and a homogeneous distribution of BGNPs in the gelatin matrix. The lamellar-type structure indicates an improvement of mechanical strength and absorption capacity of the scaffolds. Increasing the concentration of BGNPs from 0 to 50 wt% have no noticeable effect on pore orientation, but decreases porosity and pore size distribution. Increase in BGNPs content improves the compressive strength. The absorption and biodegradation rate reduces with augmentation in BGNPs concentration. Bio- activity is evaluated through apatite formation after immersion of the nanocom- posites in simulated body fluid and is verified by SEM–energy-dispersive X-ray spectroscopy (EDS), an element map analysis, X-ray powder diffractometer, and FTIR spectrum. SEM images and methyl thiazolyl tetrazolium assay confirm the biocompatibility of scaffolds and the supportive behavior of nanocomposites in cellular spreading. The results show that gelatin–(30 wt%)bioglass nanocom- posites have incipient physicochemical and biological properties. Macromol. Mater. Eng. 2018, 1700539