ORCID Profile
0000-0003-0030-7881
Current Organisation
East China University of Science and Technology
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Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.ACTBIO.2018.09.011
Abstract: Bone morphogenetic protein-2 (BMP-2) involved therapy is of great potential for bone regeneration. However, its clinical application is restricted due to the undesirable bioactivity and relevant complications in vivo. Immobilization of recombinant BMP-2 (rhBMP-2) is an efficient strategy to mimic natural microenvironment and retain its bioactivity. Herein, we present evidences indicating that osteoinductive capacity of rhBMP-2 can be regulated via variant immobilizing approaches. Three representative superficial immobilizing models were employed to fabricate rhBMP-2-immobilized surfaces including physical adsorption (Au/rhBMP-2), covalent grafting (rhBMP-2-SAM-Au) and heparin binding (Hep-SAM-Au/rhBMP-2) (SAM: self-assembled monolayer). Loading capacity, releasing behavior, osteogenic differentiation and signaling pathways involved, as well as the cellular recognition of rhBMP-2 under various immobilization modes were systematically investigated. As a result, disparate immobilizing approaches not only have effects on loading capacity, but also lead to disparity of osteoinduction at the same dosage. Notably, heparin could reinforce the recognition between rhBMP-2 and its receptors (BMPRs) whereas weaken its binding to its antagonist Noggin. Owing to this "selective" binding feature, the favorable osteoinduction and maximum ectopic bone formation can be achieved with the heparin-binding approach. In particular, manipulation of orientation-mediated BMP-2-cell recognition efficiency may be a potential target to design more therapeutic efficient rhBMP-2 delivery system. STATEMENT OF SIGNIFICANCE: Bone morphogenetic protein-2 (BMP-2) is crucial in bone regeneration. However, its clinical application is challenged due to its shorten half-life and supra-physiological dose associated complications. In this study, three representative superficial immobilizing patterns were fabricated through physical adsorption, covalent grafting and electrostatic interaction with heparin respectively. We provided evidences indicating an dose-dependent osteoinductive capacity of immobilized BMP-2. Further, a possible mechanism of rhBMP-2-cell recognition at the interface was presented, highlighting the superior effect of heparin on rhBMP-2 bioactivity. Finally, We proposed a dual mechanism of tuning the bioactivity of immobilized rhBMP-2 through surface immobilization approaches: regulation of the saturated loading capacity and orientation-mediated rhBMP-2-cell recognition. These results provide novel insights into designing criterion of efficient delivery vehicle for rhBMP-2.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.BIOMATERIALS.2019.119645
Abstract: Preserving the bioactivity of growth factors (GFs) and mimicking their in vivo supply patterns are challenging in the development of GFs-based bone grafts. In this study, we develop a 2-N, 6-O-sulfated chitosan (26SCS) functionalized dual-modular scaffold composed of mesoporous bioactive glass (MBG) with hierarchical porous structures (module I) and GelMA hydrogel columns (module II) in situ fixed in hollowed channels of the module I, which is capable of realizing differentiated delivery modes for osteogenic rhBMP-2 and angiogenic VEGF. A combinational release profile consisting of a high concentration of VEGF initially followed by a decreasing concentration over time, and a slower/sustainable release of rhBMP-2 is realized by immobilizing rhBMP-2 in module I and embedding VEGF in module II. Systematic in vitro and in vivo studies prove that the two coupled processes of osteogenesis and angiogenesis are well-orchestrated and both enhanced ascribed to the specific GFs delivery modes and 26SCS decoration. 26SCS not only enhances the GFs' bioactivity but also decreases antagonism effects of noggin. This study highlights the importance of differentiating the delivery pattern of different GFs and likely sheds light on the future design of growth factor-based bone grafts.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8BM00701B
Abstract: The immunomodulatory property of biomaterials is vital in determining the in vivo fate of implants and tissue regeneration.
No related grants have been discovered for Yuanman Yu.