Sustained release of bioactive molecules from delivery systems is a common strategy for ensuring their prolonged bioactivity and for minimizing safety issues. However, residual toxic reagents, the use of harsh organic solvents, and complex fabrication procedures in conventional delivery systems are considered enormous impediments toward clinical use. Herein, we describe bone morphogenetic protein-2 (BMP-2)-immobilized porous polycaprolactone particles with unique leaf-stacked structures (LSS particles) prepared using clinically feasible materials and procedures. The BMP-2 immobilized in these LSS particles is continuously released up to 36 days to provide an appropriate environment for osteogenic differentiation of human periosteum-derived cells and new bone formation. Thus, the leaf-stacked structures of these LSS particles provide a simple but clinically applicable platform for effectively delivering a variety of bioactive molecules, such as growth factors, hormones, cytokines, peptides, etc.
The aim of this study was to examine the effects of human umbilical cord blood-derived CD34-positive endothelial progenitor cells (CD34+ EPCs) on osteoblastic differentiation of cultured human periosteal-derived osteoblasts (POs). CD34+ cells from human umbilical cord blood were sorted to purify more EPCs in characterization. These sorted cells showed CD31, VE-cadherin, and KDR expression as well as CD34 expression and formed typical tubes in Matrigel. These sorted cells were referred to as human cord blood-derived CD34+ EPCs. In in vivo bone formation using a miniature pig model, the newly formed bone was clearly examined in defects filled with polydioxanone/pluronic F127 (PDO/Pluronic F127) scaffolds containing either human umbilical cord blood-derived CD34+ EPCs and POs or human umbilical vein endothelial cells (HUVEC) and POs; however, the new bone had the greatest density in the defect treated with CD34+ EPCs and POs. Osteoblastic phenotypes of cultured human POs using ALP activity and von Kossa staining were also more clearly found in CD34+ EPC-conditioned medium than CD34-negative (CD34-) cell-conditioned medium, whereas HUVEC-conditioned medium had an intermediate effect. PCR array for common cytokines and growth factors showed that the secretion of interleukin (IL)-1β was significantly higher in CD34+ EPCs than in HUVEC, followed by level in CD34- cells. In addition, IL-1β also potently and dose dependently increased ALP activity and mineralization of POs in culture. These results suggest that human umbilical cord blood-derived CD34+ EPCs stimulates osteoblastic differentiation of cultured human POs. The functional role of human umbilical cord blood-derived CD34+ EPCs in increasing the osteogenic phenotypes of cultured human POs may depend on IL-1β secreted from human umbilical cord blood-derived CD34+ EPCs.
Sufficient oxygen
delivery into tissue-engineered three-dimensional
(3D) scaffolds to produce clinically applicable tissues/organs remains
a challenge for researchers and clinicians. One potential strategy
to overcome this limitation is the use of an oxygen releasing scaffold.
In the present study, we prepared hollow microparticles (HPs) loaded
with an emulsion of the oxygen carrier perfluorooctane (PFO; PFO-HPs)
for the timely supply of oxygen to surrounding cells. These PFO-HPs
prolonged the survival and preserved the osteogenic differentiation
potency of human periosteal-derived cells (hPDCs)
under hypoxia. hPDCs seeded onto PFO-HPs formed new
bone at a faster rate and with a higher bone density than hPDCs seeded onto phosphate buffered saline-loaded control
HPs. These findings suggest that PFO-HPs provide a suitable environment
for the survival and maintenance of differentiation ability of hPDCs at bony defects without vascular networks until new
blood vessel ingrowth occurs, thus enhancing bone regeneration. PFO-HPs
are a promising system for effective delivery of various functional
cells, including stem cells and progenitor cells, to regenerate damaged
tissues/organs.
Although biological therapies based on growth factors and transplanted cells have demonstrated some positive outcomes for intervertebral disc (IVD) regeneration, repeated injection of growth factors and cell leakage from the injection site remain considerable challenges for human therapeutic use. Herein, we prepare human bone marrow-derived mesenchymal stem cells (hBMSCs) and transforming growth factor-β3 (TGF-β3)-loaded porous particles with a unique leaf-stack structural morphology (LSS particles) as a combination bioactive delivery matrix for degenerated IVD. The LSS particles are fabricated with clinically acceptable biomaterials (polycaprolactone and tetraglycol) and procedures (simple heating and cooling). The LSS particles allow sustained release of TGF-β3 for 18 days and stable cell adhesiveness without additional modifications of the particles. On the basis of in vitro and in vivo studies, it was observed that the hBMSCs/TGF-β3-loaded LSS particles can provide a suitable milieu for chondrogenic differentiation of hBMSCs and effectively induce IVD regeneration in a beagle dog model. Thus, therapeutically loaded LSS particles offer the promise of an effective bioactive delivery system for regeneration of various tissues including IVD.
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