Danial Barati

All Publications

• Nanoparticle-Mediated TGF-beta Release from Microribbon-Based Hydrogels Accelerates Stem Cell-Based Cartilage Formation In Vivo. Annals of biomedical engineering Barati, D., Gegg, C., Yang, F. 2020

  Abstract

  Conventional nanoporous hydrogels often lead to slow cartilage deposition by MSCs in 3D due to physical constraints and requirement for degradation. Our group has recently reported macroporous gelatin microribbon (muRB) hydrogels, which substantially accelerate MSC-based cartilage formation in vitro compared to conventional gelatin hydrogels. To facilitate translating the use of muRB-based scaffolds for supporting stem cell-based cartilage regeneration in vivo, there remains a need to develop a customize-designed drug delivery system that can be incorporated into muRB-based scaffolds. Towards this goal, here we report polydopamine-coated mesoporous silica nanoparticles (MSNs) that can be stably incorporated within the macroporous muRB scaffolds,and allow tunable release of transforming growth factor (TGF)-beta3. We hypothesize that increasing concentration of polydopamine coating on MSNs will slow down TGF- beta3 release, and TGF-beta3 release from polydopamine-coated MSNs can enhance MSC-based cartilage formation in vitro and in vivo. We demonstrate that TGF-beta3 released from MSNs enhance MSC-based cartilage regeneration in vitro to levels comparable to freshly added TGF-beta3 in the medium, as shown bybiochemical assays, mechanical testing, and histology. Furthermore, when implanted in vivo in a mouse subcutaneous model, onlythe group containing MSN-mediated TGF-beta3 release supported continuous cartilage formation, whereas control group without MSN showed loss of cartilage matrix and undesirable endochondral ossification. The modular design of MSN-mediated drug delivery can be customized for delivering multiple drugs with individually optimized release kinetics, and may be applicable to enhance regeneration of other tissue types.

  View details for DOI 10.1007/s10439-020-02522-z

  View details for PubMedID 32377980

• Injectable and Crosslinkable PLGA-Based Microribbons as 3D Macroporous Stem Cell Niche. Small (Weinheim an der Bergstrasse, Germany) Barati, D., Watkins, K., Wang, Z., Yang, F. 2020: e1905820

  Abstract

  Poly(lactide-co-glycolide) (PLGA) has been widely used as a tissue engineering scaffold. However, conventional PLGA scaffolds are not injectable, and do not support direct cell encapsulation, leading to poor cell distribution in 3D. Here, a method for fabricating injectable and intercrosslinkable PLGA microribbon-based macroporous scaffolds as 3D stem cell niche is reported. PLGA is first fabricated into microribbon-shape building blocks with tunable width using microcontact printing, then coated with fibrinogen to enhance solubility and injectability using aqueous solution. Upon mixing with thrombin, firbornogen-coated PLGA microribbons can intercrosslink into 3D scaffolds. When subject to cyclic compression, PLGA microribbon scaffolds exhibit great shock-absorbing capacity and return to their original shape, while conventional PLGA scaffolds exhibit permanent deformation after one cycle. Using human mesenchymal stem cells (hMSCs) as a model cell type, it is demonstrated that PLGA muRB scaffolds support homogeneous cell encapsulation, and robust cell spreading and proliferation in 3D. After 28 days of culture in osteogenic medium, hMSC-seeded PLGA muRB scaffolds exhibit an increase in compressive modulus and robust bone formation as shown by staining of alkaline phosphatase, mineralization, and collagen. Together, the results validate PLGA muRBs as a promising injectable, macroporous, non-hydrogel-based scaffold for cell delivery and tissue regeneration applications.

  View details for DOI 10.1002/smll.201905820

  View details for PubMedID 32338432

• IL-4 Overexpressing Mesenchymal Stem Cells within Gelatin-Based Microribbon Hydrogels Enhance Bone Healing in a Murine Long Bone Critical-size Defect Model. Journal of biomedical materials research. Part A Ueno, M., Lo, C. W., Barati, D., Conrad, B., Lin, T., Kohno, Y., Utsunomiya, T., Zhang, N., Maruyama, M., Rhee, C., Huang, E., Romero-Lopez, M., Tong, X., Yao, Z., Zwingenberger, S., Yang, F., Goodman, S. B. 2020

  Abstract

  Mesenchymal stem cell (MSC)-based therapy is a promising strategy for bone repair. Furthermore, the innate immune system, and specifically macrophages, play a crucial role in the differentiation and activation of MSCs. The anti-inflammatory cytokine IL-4 converts pro-inflammatory M1 macrophages into a tissue regenerative M2 phenotype, which enhances MSC differentiation and function. We developed lentivirus-transduced IL-4 over-expressing MSCs (IL-4 MSCs) that continuously produce IL-4 and polarize macrophages toward an M2 phenotype. In the current study, we investigated the potential of IL-4 MSCs delivered using a macroporous gelatin-based microribbon (?RB) scaffold for healing of critical size long bone defects in Mice. IL-4 MSCs within ?RBs enhanced M2 marker expression without inhibiting M1 marker expression in the early phase, and increased macrophage migration into the scaffold. Six weeks after establishing the bone defect, IL-4 MSCs within ?RBs enhanced bone formation and helped bridge the long bone defect. IL-4 MSCs delivered using macroporous ?RB scaffold is potentially a valuable strategy for the treatment of critical size long bone defects. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/jbm.a.36982

  View details for PubMedID 32363683