Hybrid use of combined and sequential delivery of growth factors and ultrasound stimulation in porous multilayer composite scaffolds to promote both vascularization and bone formation in bone tissue engineering

Abstract

In this study, a multilayer coating technology would be adopted to prepare a porous composite scaffold and the growth factor release and ultrasound techniques were introduced into bone tissue engineering to finally solve the problems of vascularization and bone formation in the scaffold whilst the designed multilayer composite with gradient degradation characteristics in the space was used to match the new bone growth process better. The results of animal experiments showed that the use of low intensity pulsed ultrasound (LIPUS) combined with growth factors demonstrated excellent capabilities and advantages in both vascularization and new bone formation in bone tissue engineering. The degradation of the used scaffold materials could match new bone formation very well. The results also showed that only RGD-promoted cell adhesion was insufficient to satisfy the needs of new bone formation while growth factors and LIPUS stimulation were the key factors in new bone formation.

Biophysical Stimuli as the Fourth Pillar of Bone Tissue Engineering

“…For example, Parmaksiz et al transplanted DBM and DBM containing magnetic particles to bilateral critical-size cranial defects of rats with or without PEMF exposure, and results revealed that exposed groups of DBM and DBM containing magnetic particles show improved bone regeneration and reduced fibrous formation compared with unexposed groups (Parmaksiz et al, 2021). Yan et al also verified that postoperative LIPUS could promote the healing of rabbit femurs defects (Yan et al, 2016). Therefore, postoperative biophysical stimuli loading strategies show great promise in bone tissue engineering, but they remain poorly explored.…”

In Vivo Bone Tissue Engineering Strategies: Advances and Prospects

“…Previous studies have revealed key components of BTE [ 21 , 22 , 23 , 24 , 25 , 26 ]. According to these studies successful bone regeneration relies on the combination of (1) a bioactive scaffold [ 27 , 28 , 29 , 30 , 31 ]; (2) osteoprogenitor cells [ 21 , 26 , 32 , 33 , 34 , 35 ]; (3) growth factors (GF) [ 23 , 36 , 37 , 38 , 39 , 40 ] and (4) adequate vascularization [ 41 , 42 , 43 ] ( Figure 1 ).…”

“…Previous studies have revealed key components of BTE [21][22][23][24][25][26]. According to these studies successful bone regeneration relies on the combination of (1) a bioactive scaffold [27][28][29][30][31]; (2) osteoprogenitor cells [21,26,[32][33][34][35]; (3) growth factors (GF) [23,[36][37][38][39][40] and (4) adequate vascularization [41][42][43] (Figure 1). Natural polymers are particularly effective for regenerative medicine application for two main reasons.…”

Tissue Engineering and Regenerative Medicine: Achievements, Future, and Sustainability in Asia

“…In addition, they also found the function of modulating immunity and inducing immune tolerance of allogeneic mesenchymal stromal cells (Peng et al, 2012). Likewise, growth factors such as BMP-2 and TGF-β1 and vascular endothelial growth factor (VEGF) are also introduced to scaffolds to enhance bone repair (Qu et al, 2015;Yan et al, 2016). Yang's group developed PLGA/PCL scaffold modified by silver impregnation, collagen coating, and electrospinning; this scaffold showed osteogenic and antimicrobial properties for orofacial tissue regeneration (Qian et al, 2019).…”