Assessment of Polymer/Bioactive Glass-Composite Microporous Spheres for Tissue Regeneration Applications

Abstract

Conformable scaffold materials capable of rapid vascularization and tissue infiltration would be of value in the therapy of inaccessible wounds. Microporous spheres of poly(D,L-lactide-co-glycolide) (PLGA) containing bioactive glass (BG) were prepared using a thermally induced phase separation (TIPS) technique, and the bioactivity, in vitro degradation, and tissue integration of the microporous spheres were assessed. Microporous spheres containing 10% (w/w) BG stimulated a significant increase in vascular endothelial growth factor secretion from myofibroblasts consistently over a 10-day period (p < 0.01) compared with the neat PLGA microporous spheres. The microporous spheres degraded steadily in vitro over a 16-week period, with the neat PLGA microporous spheres retaining 82% of their original weight and microporous spheres containing 10% (w/w) BG retaining 77%. Both types of microporous spheres followed a similar pattern of size reduction throughout the degradation study, resulting in a 23% and 20% reduction after 16 weeks for the neat PLGA microporous spheres and PLGA microporous spheres containing 10% (w/w) BG, respectively (p < 0.01). After in vivo implantation into a subcutaneous wound model, the TIPS microporous spheres became rapidly integrated (interspherically and intraspherically) with host tissue, including vascularization of voids inside the microporous sphere. The unique properties of TIPS microporous spheres make them ideally suited for regenerative medicine applications where tissue augmentation is required.

A Novel Method for Differentiation of Human Mesenchymal Stem Cells into Smooth Muscle-Like Cells on Clinically Deliverable Thermally Induced Phase Separation Microspheres

“…29 We have also shown that TIPS microspheres retain an open scaffold structure when implanted in vivo, which facilitates rapid tissue infiltration and integration at the site of implantation, thus reducing the possibility of migration from the target site. 40 Results from the current study indicate that it is possible to achieve smooth muscle-like cells from AdMSCs when incubated on TIPS microcarriers. Further studies will be necessary to prove that the differentiated cells are capable of providing phasic and tonic contractile properties similar to native smooth muscle and that they can restore damaged or lost smooth muscle function.…”

“…29,31,40 Relative to solid microcarriers, TIPS microcarriers of an equal size contain approximately 80-90% less polymer material. 40 This is advantageous as less degradation products are produced as the microcarriers degrade to be replaced by host tissue. The open porous structure also allows surface erosion to occur rather than an autocatalytic process that is associated with solid PLGA microspheres due to entrapment and accumulation of acidic degradation products.…”

Bioactive glass and glass-ceramic scaffolds for bone tissue engineering

“…In vivo results have confirmed that BG is able to stimulate and promote neo-vascularization [52,55,[120][121][122]164,203,206,[208][209][210][211]. For example, Leu et al [211] filled calvarial defects in SpragueDawley rats with 45S5 Bioglass ® impregnated (1.2 mg) collagen sponges (volume = 0.05 cm 3 ) and unloaded, empty sponge as a control.…”

“…In 2003, Boccaccini and Maquet [42] reported for the first time on the successful fabrication of porous foam-like bioactive glass containing poly(lactide-co-glycolide) (PLGA) composites, which exhibited well-defined, oriented and interconnected porosity. Since then, many studies have been carried out to optimize and investigate bone TE composite scaffolds concerning material combinations, bioactive properties, degradation characteristics [161,164,165,168], in vitro [47,[161][162][163]169] and in vivo behavior [47,164], as well as mechanical properties [50,81,160].…”

“…Extensive work has been also carried out to investigate the cellular response to bioactive glass containing composites concerning composition, particle concentration and particle size effect in vitro and in vivo [46][47][48][161][162][163][164]166,[169][170][171]174]. For example, Lu et al [179] showed that for PLGA/bioactive glass films (0, 10, 25, 50 wt %), the growth, mineralization and differentiation of human osteoblast-like SaOS-2 cells (Figure 15), as well as the kinetics of Ca-P layer formation and the resulting Ca-P chemistry were dependent on BG content.…”