A 3D-bioprinted scaffold with doxycycline-controlled BMP2-expressing cells for inducing bone regeneration and inhibiting bacterial infection

Abstract

Large bone defects face a high risk of pathogen exposure due to open wounds, which leads to high infection rates and delayed bone union. To promote successful repair of infectious bone defects, fabrication of a scaffold with dual functions of osteo-induction and bacterial inhibition is required. This study describes creation of an engineered progenitor cell line (C3H10T1/2) capable of doxycycline (DOX)-mediated release of bone morphogenetic protein-2 (BMP2). Three-dimensional bioprinting technology enabled creation of scaffolds, comprising polycaprolactone/mesoporous bioactive glass/DOX and bioink, containing these engineered cells. In vivo and in vitro experiments confirmed that the scaffold could actively secrete BMP2 to significantly promote osteoblast differentiation and induce ectopic bone formation. Additionally, the scaffold exhibited broad-spectrum antibacterial capacity, thereby ensuring the survival of embedded engineered cells when facing high risk of infection. These findings demonstrated the efficacy of this bioprinted scaffold to release BMP2 in a controlled manner and prevent the occurrence of infection; thus, showing its potential for repairing infectious bone defects.

Felodipine enhances aminoglycosides efficacy against implant infections caused by methicillin-resistant Staphylococcus aureus, persisters and biofilms

“…In addition, drug-carrying nanorobots with penetrating function can also be used to increase the concentration of drugs within biofilms, thus further enhancing the efficacy of removing biofilms [ 54 ]. Of course, more drug-loaded bioactive materials might be developed to enhance the anti -biofilm efficacy of felodipine, such as 3D printed biomaterials [ 37 ].…”

“…All in vivo animal experimental procedures were approved and performed in accordance with the guidelines of the Animal Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine, China. To examine the antibacterial effects of felodipine alone, skin and soft tissue infections caused by S. aureus were conducted following a previously described protocol [ [35] , [36] , [37] ] with some modifications. Briefly, eight-week-old female CD1 ICR outbred mice (25–30 g) were purchased from Shanghai JieSiJie Laboratory Animal Co., Ltd. and randomly divided into four groups: 1) vehicle, 2) gentamicin, 3) low-dose felodipine, and 4) high-dose felodipine.…”

3D scaffolds in the treatment of diabetic foot ulcers: New trends vs conventional approaches

“…In general, bioprinting offers several advantages, including the production of scaffolds with a highly porous structure that are capable of supporting cell adhesion and proliferation and allowing oxygen to permeate through the structure to ensure nutrient transport to the innermost sections of the scaffold. High loading of cells and growth factors can also be achieved (Wang et al, 2021), although the extent to which this is achieved varies between bioprinting methods.…”

Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma

“…In recent years, 3D bioprinting technologies have made great progress in replicating the delicate architecture of different tissues and mimicking the realistic in vivo microenvironment due to its ability to deposit supporting biomaterials and living cells at the same time in a cell-friendly manner [ [13] , [14] , [15] ]. In addition, 3D-bioprinting is an ideal tool applied in organ modelling, multifunctional tissue repairing, and the production of biological sensors [ [16] , [17] , [18] , [19] , [20] , [21] ].…”