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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (2) : 189-201
Hybrid polymer biomaterials for bone tissue regeneration
Bo Lei1, Baolin Guo1, Kunal J. Rambhia2, Peter X. Ma1,2,3,4,5()
1. Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an 710054, China
2. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
3. Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA
4. Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, USA
5. Department of Material Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA
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Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity. However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications. There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers. The review further exemplifies their applications for bone tissue regeneration.

Keywords hybrid polymer      bone regeneration      tissue engineering      biomaterials     
Corresponding Authors: Peter X. Ma   
Just Accepted Date: 04 September 2018   Online First Date: 31 October 2018    Issue Date: 28 March 2019
 Cite this article:   
Bo Lei,Baolin Guo,Kunal J. Rambhia, et al. Hybrid polymer biomaterials for bone tissue regeneration[J]. Front. Med., 2019, 13(2): 189-201.
Fig.1  Bioactive glass particles reinforced PCL osteoconductive hybrid polymers. Reproduced from Ref. [41] with permission.
Fig.2  Schematic illustration of a hypothesized mechanism for the growth of calcium phosphate crystals over time. When a deposition voltage is applied, pH in the vicinity of electrode increases, and some calcium phosphate crystals deposited onto the surface of PLLA nanofibers. Further increase of deposition time leads to the generation of hydrogen bubbles and larger flower-like crystals. Reproduced from Ref. [50] with permission.
Fig.3  Formation mechanism of the biomimetic siloxane-gelatin (SGT) hybrid bone implants. (A–C) Molecular structure and composition of gelatin (GT) (A), siloxane (GS), silicate bioactive glass sol (S); (D–F) GT (D) polymer matrix was cross-linked by GS (E), and then hybridized with the SBG sol at the molecular and nanoscale levels (F); (G and H) semi-transparent SGT hybrid implants with different SBG weight percent, formed after condensation and drying. Reproduced from Ref. [51] with permission from the Royal Society of Chemistry.
Fig.4  Schematic diagram showing an experimental procedure for producing anisotropic porous gelatin-silica hybrid polymer scaffolds by ammonium hydroxide treatment. Reproduced from Ref. [68] with permission.
Fig.5  Porous morphology of gelatin-silica hybrid polymer scaffolds. (A, C) Transverse direction; (B, D) Axial direction. Reproduced from Ref. [68] with permission.
Fig.6  Schematic diagram showing an experimental procedure for producing nanofibrous gelatin-silica hybrid scaffolds by the thermally induced phase separation (TIPS) technique using the mixtures of the gelatin solution and sol–gel derived silica sol. Reproduced from Ref. [59] with permission from the Royal Society of Chemistry.
Fig.7  Synthesis of multifunctional silica-poly(citrate)-based hybrid prepolymers and elastomers. (A,B) Fabrication of multifunctional silica-poly(citrate) (MSPC)?and crosslinked?MSPC (CMSPC) elastomers?by?polycondensation?of citric acid (CA), 1,8-octylene glycol (OD), aminosilane (AS),?as?well?as?the?chemical?crosslinking?with hexamethylene diisocyanate?(HDI) and (C) schematic diagram showing the formation of CMSPC hybrid elastomers matrix. Reproduced from Ref. [30] with permission.
Fig.8  Schematic illustration for preparing poly(glycerol sebacate)-silica-calcium (PGSSC) hybrid elastomers. (A) Synthesis of PGS pre-polymers; (B) formation of silica-based bioactive glass sols; (C) fabrication of PGSSC hybrid elastomers; (D) optical images of PGS and PGSSC hybrid elastomers: (a) PGS; (b) PGS15mol%Si (PGS15Si); and (c) PGS-15mol%Si-20mol%Ca (PGS15Si20Ca). Reproduced from Ref. [29] with permission from the Royal Society of Chemistry.
Fig.9  In vitro biomineralization activity and osteoblast biocompatibility (MC3T3-E1) of BG micro-nanoscale particles-PCL hybrid polymers. (A, B) Apatite formation on surface of PCL (A) and BG-PCL (B) after soaking in SBF for 7 days; (C, D) Cell attachment morphology on the surface of PCL (C) and BG-PCL (D) after culture for 3 days. Reproduced from Refs. [41] and [43] with permission.
Fig.10  Quantitative RT-PCR results of bone sialoprotein (BSP)(A) and osteocalcin (OCN)(B) gene expression. MC3T3-E1 cells were cultured on NF-gelatin and NF-gelatin/apatite scaffolds for 1 and 4 weeks. The Y-axis of the figure is the gene expression results normalized by β actin. * represents statistically significant differences (P<0.05). Reproduced from Ref. [49] with permission.
Fig.11  Micro-computed tomography of the cranial defects (diameter=6 mm) in New Zealand White rabbits after 4-week implantation using PLGA, PLGA/TCP composites. (A, B) Two examples of the CT of the entire cranial bone are shown. Defect margins and treatment modalities are indicated. Adapted from Ref. [92] with permission.
Fig.12  Optical micrographs of the rat bone tissue regeneration responses after the 3 weeks implantation of the membranes: (A, C) pure chitosan and (B, D) the chitosan–silica xerogel hybrid. The fresh-formed bone tissue was revealed in blue, the calcified bones and materials were stained in red. Reproduced from Ref. [93] with permission.
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