Induced Pluripotent Stem Cell-derived Mesenchymal Stem Cell Seeding on Biofunctionalized Calcium Phosphate Cements

Induced pluripotent stem ceils （iPSCs） have great potential due to their proliferation and differentiation capability. The objectives of this study were to generate iPSC-derived mesenchymal stem cells （iPSC-MSCs）, and investigate iPSC-MSC proliferation and osteogenic differentiation on calcium phosphate cement （CPC） containing biofunctional agents for the first time. Human iPSCs were derived from marrow CD34＋ cells which were reprogrammed by a single episomal vector, iPSCs were cultured to form embryoid bodies （EBs）, and MSCs migrated out of EBs. Five biofunctional agents were incorporated into CPC： RGD （Arg-Gly-Asp） peptides, fibronectin （Fn）, fibronectin-like engineered polymer protein （FEPP）, extracellular matrix Geltrex, and platelet concentrate, iPSC-MSCs were seeded on five biofunctionalized CPCs： CPC-RGD, CPC-Fn, CPC- FEPP, CPC-Geltrex, and CPC-Platelets. iPSC-MSCs on biofunctional CPCs had enhanced proliferation, actin fiber expression, osteogenic differentiation and mineralization, compared to control. Cell proliferation was greatly increased on biofunctional CPCs. iPSC-MSCs underwent osteogenic differentiation with increased alkaline phosphatase, Runx2 and coUagen-I expressions. Mineral synthesis by iPSC-MSCs on CPC-Platelets was 3-fold that of CPC control. In conclusion, iPSCs showed high potential for bone engineering, iPSC- MSCs on biofunctionalized CPCs had cell proliferation and bone mineralization that were much better than traditional CPC. iPSC-MSC-CPC constructs are promising to promote bone regeneration in craniofacial/ orthopedic repairs.

Inhibition of CCL2 by bindarit alleviates diabetes-associated periodontitis by suppressing inflammatory monocyte infiltration and altering macrophage properties

Diabetes-associated periodontitis(DP)aggravates diabetic complications and increases mortality from diabetes.DP is caused by diabetes-enhanced host immune-inflammatory responses to bacterial insult.In this study,we found that persistently elevated CCL2 levels in combination with proinflammatory monocyte infiltration of periodontal tissues were closely related to DP.Moreover,inhibition of CCL2 by oral administration of bindarit reduced alveolar bone loss and increased periodontal epithelial thickness by suppressing periodontal inflammation.Furthermore,bindarit suppressed the infiltration of proinflammatory monocytes and altered the inflammatory properties of macrophages in the diabetic periodontium.This finding provides a basis for the development of an effective therapeutic approach for treating DP.

3D-printed Mechanically Strong Calcium Phosphate Cement Scaffold with Metformin/Stem Cell-encapsulating Alginate Microbeads for Bone Tissue Engineering

The utilization of Calcium Phosphate Cement(CPC)is limited due to its low mechanical strength and difficulty to seed cells deep into the scaffold.The objectives of this study were to:(1)develop a 3D-printed CPC-dopamine-metformin scaffold encapsulating human periodontal ligament stem cells(hPDLSCs),(2)investigate the effect of dopamine on the performance of CPC,and(3)evaluate the effect of microbead degradation and metformin release on the osteogenic differentiation of the released hPDLSCs.The mechanical property of the CPC scaffolds was elevated by adding dopamine,and the CPC scaffold with 7 wt.%dopamine had the highest compressive strength(7.35 MPa).Four types of microbeads with different content of alginate(oxidized alginate),hPDLSCs,and 2%metformin were fabricated.Morphological and cell counting kit tests confirm that the hPDLSCs are protected by microbeads encapsulation during the CPC setting process.The alkaline phosphatase test indicates that the osteogenic differentiation of hPDLSCs was enhanced by the fast release of cells and metformin.The microbeads consisting of 2%oxidized alginate and 2%metformin were optimal for cell delivery due to favorable cell release and osteogenic differentiation.This CPC scaffold is promising used for bone regeneration in dental,craniofacial,and orthopedic applications.