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SCIENCE CHINA Chemistry, Volume 61, Issue 12: 1553-1567(2018) https://doi.org/10.1007/s11426-018-9324-0

Biomineralized polymer matrix composites for bone tissue repair: a review

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  • ReceivedMay 14, 2018
  • AcceptedJul 9, 2018
  • PublishedOct 30, 2018

Abstract

Bone defects caused by trauma, infection or bone tumor resection, are highly prevalent. A small number (5%–10%) of these injuries fail to heal due to non-union and require surgical intervention. Currently, the principal treatment options for these defects are autografts, allografts, xenografts or synthetic grafts. The main problems associated with these therapies include pain, infection and donor site morbidity. Bone tissue engineering is a diverse field that focuses on the regeneration of bone by combining cells, scaffolds, growth factors and dynamic forces. There have been many recent studies utilizing biomineralized polymer matrix composites which mimic the natural structure of bone. The principal focus of this review is on recent advances in the synthesis of various types of biomineralized polymer matrix composite. Examples of the biomineralization of naturally-derived and synthetic polymers widely used for bone engineering are also summarized.


Funded by

The National Key Research and Development Program of China(2017YFC1103500,2017YFC1103502)

the National Natural Science Foundation of China(31525009)

Sichuan Innovative Research Team Program for Young Scientists(2016TD0004)

Distinguished Young Scholars of Sichuan University(2011SCU04B18)

and Sichuan Science and Technology Project(2017GZ0429)


Acknowledgment

This work was supported by the National Key Research and Development Program of China (2017YFC1103500, 2017YFC1103502), the National Natural Science Foundation of China (31525009), Sichuan Innovative Research Team Program for Young Scientists (2016TD0004), Distinguished Young Scholars of Sichuan University (2011SCU04B18), and Sichuan Science and Technology Project (2017GZ0429).


Interest statement

The authors declare that they have no conflict of interest.


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  • Figure 1

    Theories of biomineralization process of collagen. (A) Process of direct nucleation of CaP crystal; (B) three possible process of MV-mediated matrix mineralization. Reprinted with permission from Ref. [55], copyright © 2012 Acta Materialia Inc. (color online).

  • Figure 2

    A schematic representation of the proposed mechanism for silk fibroin microsphere control of the biomineralization process of CaCO3, which including the nucleation (a), growth (b), aggregation (c) and self-assembly (d). Reprinted with permission from Ref. [80], copyright © 2013 Acta Materialia Inc. (color online).

  • Figure 3

    SEM images of a PLA foam incubated in SBF for 30 d. Reprinted with permission from Ref. [99], copyright © 1999 John Wiley & Sons, Inc.

  • Figure 4

    SEM images of PLGA electrospun nanofibers. (a) Without surface treatments; (b) treated with plasma; (c) treated with plasma and then chitosan; (d) treated with plasma, chitosan, and then heparin. All the nanofibers followed by immersion in m10SBF (with a concentration of 42 mM for HCO3) for 3 h. Reprinted with permission from Ref. [124], copyright © 2011 American Chemical Society.

  • Figure 5

    SEM images of mineralized PCL-membrane, PCL/PEG membrane with nano-nets (PG40) and PCL/PEG membrane without nano-nets (PG40A). The membranes were soaked in SBF fluid for 1 or 2 weeks at 37 °C. Reprinted with permission from Ref. [141], copyright © 2017 Elsevier B.V.

  • Figure 6

    (a–d) SEM images of PHBV scaffold incubated in 100 mM CaCl2/Tris and Na2HPO4/Tris solutions alternatively for 1, 3, 5, 7 cycles respectively. Images in the right column of (a–d) show the high-resolution SEM images. Reprinted with permission from Ref. [145], opyright © 2007 Elsevier B.V.

  • Figure 7

    (a) SEM images of as prepared pure PU and PU/ZnO-fMWCNTs composite electrospun nanofiber scaffolds after immersion in SBF solution for 3 and 7 d; (b) EDX results of PU and PU/ZnO-fMWCNTs (0.4 wt%) mats after 3 d incubation in SBF solution. Reprinted with permission from Ref. [154], copyright © 2017 Elsevier B.V. (color online).

  • Table 1   Summary of biomineralized matrix materials and their advantages and disadvantages

    ƒMaterials

    Pros

    Cons

    ƒChitosan

    • Non-toxicity, biodegradability, biocompatibility

    • Good antimicrobial ability

    • Can act as a template for biomineralization due to the presence€of –NH2 and –C=O functional groups

    • High degree of crystallinity and rigid mechanical properties

    • Hydrophobic properties

    ƒCollagen

    • Can be easily degraded and absorbed by human body

    • Can mediate HA formation

    • Oxygen atoms of the carboxyl and carbonyl can become the core€of the heterogeneous nucleation

    • Some 3D scaffolds have to undergo crosslinking to improve€the mechanical strength

    • Need to be dissolved by acids first

    ƒGelatin

    • Compared to collagen, the water solubility of gelatin is higher

    • Have a large number of hydroxyl groups, carboxyl groups and amino€groups which could effectively induce the formation of mineral

    • Insufficient mechanical properties

    ƒSilk proteins

    • Excellent mechanical strength

    • Good biocompatibility and properties of intercellular signaling

    • Pure silk fibroin do not possess osteoconductive property

    • Limited access to obtain

    • The properties and structure vary depending on the different€breeds

    ƒPLA

    • Good biocompatibility and non-toxicity

    • Hydrolysis of –COOH groups lead the polymer surface negatively€charged and can bind to Ca2+

    • Hydrophobic

    • Lack of cell recognition sites and acidic degradation€products.

    ƒPGA

    • Composed of a hydrophilic, anionic, biodegradable and biologically€compatible polypeptide

    • Contain abundant –COOH groups lead to excellent apatite-forming€ability in SBF solution

    • Difficulty in manufacturing

    • Rigid mechanical properties

    ƒPLGA

    • Tunable degree of crystallization, mechanical properties, and€degradation rate

    • Have better processability compared with PGA

    • Lack cell-affinitive ability when used as substrate materials€for cell attachment

    ƒPCL

    • Sufficient mechanical properties, good processability, ability to€support early loads and compatibility with different polymers

    • Lacking functional groups lead to its poor cell attachment

    • Stable in ambient conditions and degrade very slow

    ƒPHA

    • Good mechanical properties and degradation rates depending on the€chemical structure

    • Synthesized by microorganisms fermentation through various carbon€sources

    • Some PHA degrade very slow

    ƒPU

    • Good mechanical strength,

    • Biodegradability and biocompatibility can be easily modified by€adjusting the components of the hard and soft segments during€synthesis

    • Sensitivity to free radicals and therefore it is prone to attacksfrom phagocytes, leading to immune responses.

    • Lack bioactive groups to facilitate biomineralization

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