Enhanced Osteogenesis of Bone Marrow‐Derived Mesenchymal Stem Cells by a Functionalized Silk Fibroin Hydrogel for Bone Defect Repair

Abstract

effective for bone defect treatment and bone reconstruction, these approaches are limited in their clinical application by certain constraints such as i) tissue morbidity at donor sites and the limited availability of autologous bone as well as ii) the high risk of infection and immunogenic rejection with allografts. [5][6][7][8][9] To overcome the limitations of autografting and allografting, various materials, including metals, ceramics, and polymers, have been investigated as bone scaffold biomaterials for bone graft substitutes. [10][11][12] In some cases, these scaffolds often suffer from low cell adhesion, insufficient bioactivity, or uncontrolled degradability. Therefore, the development of new classes of biomaterials for bone regeneration has been the focus of research in the fields of bone tissue engineering. [13][14][15] Ideal biomaterials for bone regeneration should provide temporary structural scaffolds with suitable mechanical strength and possess bioactive elements for cell adhesion, proliferation, differentiation of tissue regenerating cells, and the generation of a new mineralized bone matrix. [16,17] Over the last decade, hydrogels have emerged as a promising class of biomaterials for the fabrication of both bone scaffolds and bone-engineering tissues due to their high water content, structural similarity to natural extracellular matrices (ECM), [18][19][20][21] and tailorable physical and biochemical properties. [22] In contrast to rigid biomaterials from ceramics and metals, hydrogels exhibit a high degree of flexibility and toughness. Therefore, after implantation via minimally invasive surgical techniques, hydrogels are capable of fitting the lesion geometry of defects and establish tight contacts with host tissues to achieve better cell adhesion and therapy. [23][24][25] Moreover, recent advances in the development of cell-laden hydrogels have opened up a new opportunity for bone repair and regeneration. [26][27][28] Hydrogels act as 3D scaffolds providing suitable microenvironments for cell proliferation, differentiation, and maintenance of function, thus allowing exogenous cells to grow and secrete new ECM for the reconstruction of damaged bone tissues. [29,30] Mesenchymal stem cells (MSCs) are multipotent stromal cells originating from umbilical cord, muscle, and bone Silk fibroin (SF) from Bombyx mori is a promising natural material for the synthesis of biocompatible and biodegradable hydrogels for use in biomedical applications from tissue engineering to drug delivery. However, weak gelation performance and the lack of biochemical cues to trigger cell proliferation and differentiation currently significantly limit its application in these areas. Herein, a biofunctional hydrogel containing SF (2.0%) and a small peptide gelator (e.g., NapFFRGD = 1.0 wt%) is generated via cooperative molecular self-assembly. The introduction of NapFFRGD to SF is shown to significantly improve its gelation properties by lowering both its threshold gelation concentration to 2.0% and gelation time to 20 min ...

Human Adipose-Derived Mesenchymal Stem Cells-Incorporated Silk Fibroin as a Potential Bio-Scaffold in Guiding Bone Regeneration

“…In clinical applications, cell viability is an important parameter for evaluating the scaffold capacity to generate successful cell-biomaterial constructs. Previous studies have demonstrated that cell viability and proliferation were promoted by SF [34,35]. In this study, the SF scaffold cytotoxicity was evaluated on cultured hASCs for two weeks.…”

“…Previous studies have reported the osteogenic abilities of stem cells-incorporated SF to stimulate new bone formation using different scaffold designs and animal models [35,49,50]. Yan et al demonstrated that, besides mediating cell adhesion, the RGD ligands incorporated within their SF-RGD gel promoted the osteogenic differentiation of bone marrow-derived mesenchymal stem cells encapsulated within the gel matrix, leading to bone regeneration in a mouse calvarial defect model, compared with a blank SF gel [35]. Further, the functionalized SF-GO-BMP-2 composite scaffold displayed good biocompatibility and excellent proliferation effects and biological activity, thus improving bone regeneration in critical-sized bone defects and enhancing the osteogenic differentiation of BMSCs [49].…”

Immunotherapeutic silk inverse opal particles for post-surgical tumor treatment

“…1. Silk fibroin, extracted from Bombyx mori cocoons, is a widely studied and used natural fibrous protein for diverse biomedical applications because of its advantages of abundant sources, excellent biocompatibility, great biodegradability, low toxicity and non-immunogenic features [34][35][36][37]. Although the silk materials have been employed for the drug delivery systems, most of them are merely prepared into simple morphologies or structures with less controllable capabilities due to the lack of elaborate design; this greatly limits their practical applications [38,39].…”

High-Strength Albumin Hydrogels With Hybrid Cross-Linking

“…However, the poor mechanical properties of natural protein hydrogels is one of the main drawbacks impeding their application in some cases (Silva et al, 2017;Tang et al, 2018). Recently, great efforts have been made to enhance the mechanical properties of natural protein hydrogels, and some strategies have been developed, including nanocomposite (Yuk et al, 2016;Qin et al, 2017;Wang et al, 2017Wang et al, , 2018, physical cross-linking (Toivonen et al, 2015;Feng et al, 2018;Yan et al, 2019;Zhang et al, 2019), solvent induction (Li et al, 2016;Zhang et al, 2016;Hashemnejad et al, 2017;Zhu et al, 2018), double network (Bhattacharjee et al, 2015;Luo et al, 2016;Rangel-Argote et al, 2018;Tavsanli and Okay, 2019), hybrid cross-linking (Moura et al, 2011;Epstein-Barash et al, 2012;Xu et al, 2016;Nojima and Iyoda, 2018;Yang et al, 2018), and so on.…”