Bioactive Scaffold Fabricated by 3D Printing for Enhancing Osteoporotic Bone Regeneration

Abstract

We develop a poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP)-based scaffold through a three-dimensional (3D) printing technique incorporating icaritin (ICT), a unique phytomolecule, and secretome derived from human fetal mesenchymal stem cells (HFS), to provide mechanical support and biological cues for stimulating bone defect healing. With the sustained release of ICT and HFS from the composite scaffold, the cell-free scaffold efficiently facilitates the migration of MSCs and promotes bone regeneration at the femoral defect site in the ovariectomy (OVX)-induced osteoporotic rat model. Furthermore, mechanism study results indicate that the combination of ICT and HFS additively activates the Integrin–FAK (focal adhesion kinase)–ERK1/2 (extracellular signal-regulated kinase 1/2)–Runx2 (Runt-related transcription factor 2) axis, which could be linked to the beneficial recruitment of MSCs to the implant and subsequent osteogenesis enhancement. Collectively, the PLGA/TCP/ICT/HFS (P/T/I/S) bioactive scaffold is a promising biomaterial for repairing osteoporotic bone defects, which may have immense implications for their translation to clinical practice.

Integrating bioprinting, cell therapies and drug delivery towards in vivo regeneration of cartilage, bone and osteochondral tissue

“…The use of endogenous protective systems, e.g. secretome [ 142 , 143 ], has been proposed as an alternative to the use of growth factors for bone TE. Secretome is defined as a set of secreted membrane-enclosed vesicles containing free nucleic acids and soluble proteins [ 144 ].…”

“…According to some works present in literature, secretome derived from human fetal MSCs promoted osteogenic differentiation of adult MSCs and enhanced bone consolidation in vivo [ 142 ]. From this perspective, Zhang et al [ 143 ] proposed a combination of secretome derived from human fetal MSCs and from icaritin (ICT). ICT is an intestinal metabolite derived from the Chinese traditional medical plant Epimedium capable to promote the proliferation and differentiation of osteoblasts and enhance matrix calcification due to its estrogenic-like activity [ 145 , 146 ].…”

“…ICT is an intestinal metabolite derived from the Chinese traditional medical plant Epimedium capable to promote the proliferation and differentiation of osteoblasts and enhance matrix calcification due to its estrogenic-like activity [ 145 , 146 ]. This combination was able to improve the bioactive properties of a PLGA/TCP-based scaffold favouring the recruitment and differentiation of endogenous MSCs towards the osteoblast lineage in vitro [ 143 ]. Moreover, in vivo experiments in an osteoporotic bone defect rat model showed that the designed system promoted bone regeneration at the defect sites.…”

Photobiomodulation Therapy Improves Repair of Bone Defects Filled by Inorganic Bone Matrix and Fibrin Heterologous Biopolymer

“…This event is stimulated by the production of chemical mediators by macrophages and platelets and, through these vessels, the migration of undifferentiated or poorly differentiated cells occurs, which subsequently differentiate and take on their function in the tissue, such as the production of extracellular matrix. The newly formed vessels and undifferentiated cells are supported by a threedimensional fibrin network formed by the blood clot or exudate [1,2].…”

“…For repair to occur effectively, it depends on a number of factors, such as care taken with the surgical environment, surgical margins, vascular proliferation, migration of undifferentiated cells, the presence of a fibrin network and, when possible, preserving the periosteum and endosteum [9][10][11]. When bone repair does not take place in the injured area, the lesion will be filled with fibrous connective tissue and the tissue will not recover its original functionality [1,12,13]. In cases where one of these factors cannot be preserved, biomaterials can be used to recompose the bone tissue [14][15][16][17].…”