Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions

Chen，Xin1; Tan，Baoyu1; Wang，Shang1; Tang，Rongze1; Bao，Zhiteng1; Chen，Gaoyang1; Chen，Shuai2; Tang，Wanze3; Wang，Zhenmin1; Long，Canling1; Lu，William W.4; Yang，Dazhi1; Bian，Liming5; Peng，Songlin1

2021-07-01

10.1016/j.biomaterials.2021.120895

BIOMATERIALS   影响因子和分区

0142-9612

1878-5905

The development of recombinant protein cross-linked injectable hydrogels with good mechanical strength and effective drug loading capacity for bone regeneration is extremely attractive and rarely reported. Here, we report the fabrication of a smart hydrogel delivery system by incorporating a rationally designed T4 lysozyme mutant (T4M) to mediate the localized delivery and synergistic release of Mg and Zn for bone repair. Apart from its intrinsic antibacterial properties, T4M bears abundant free amine groups on its surface to function as effective covalent crosslinkers to strengthen the hydrogel network as well as exhibits specific binding affinity to multivalent cations such as Zn. Moreover, the integrin receptor-binding Arg-Gly-Asp (RGD) sequence was introduced onto the C-terminus of T4 lysozyme to improve its cellular affinity and further facilitate rapid tissue regeneration. The final composite hydrogel displays excellent injectability, improved mechanical properties, antibacterial activity, and unique bioactivities. The effective loading of Mg/Zn in the hydrogels could mediate the sequential and sustained release of Mg and Zn, thereby resulting in synergistic enhancement on bone regeneration through modulation of the MAPK signaling pathway. We believe that the strategy proposed in this paper opens up a new route for developing protein cross-linked smart delivery systems for tissue regeneration.

Bone-tissue engineering Protein crosslinker Protein engineering Smart delivery system Synergistic effect of bioactive ions

SCI ; EI

英语

第一 ; 通讯

National Natural Science Foundation of China[81902199] ; Shenzhen Municipal Science and Technology Innovation Committee Project["JCYJ20190806160407178","JCYJ20180305164659637","JCYJ20180305164544288","JSGG201805 04170427135","SGLH20180625141602256","JCYJ2017041362104773"] ; Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration[ZDSYS20200811143752005]

Engineering ; Materials Science

Engineering, Biomedical ; Materials Science, Biomaterials

WOS:000663586500001

ELSEVIER SCI LTD

20212110405574

Binding energy ; Biomechanics ; Bone ; Controlled drug delivery ; Enzymes ; Magnesium ; Recombinant proteins ; Targeted drug delivery ; Tissue regeneration ; Zinc

Biomedical Engineering:461.1 ; Biological Materials and Tissue Engineering:461.2 ; Biomechanics, Bionics and Biomimetics:461.3 ; Magnesium and Alloys:542.2 ; Zinc and Alloys:546.3 ; Alkaline Earth Metals:549.2 ; Colloid Chemistry:801.3 ; Physical Chemistry:801.4 ; Chemical Products Generally:804 ; Organic Compounds:804.1

MATERIALS SCIENCE

2-s2.0-85106306759

Scopus

1.Department of Spine Surgery and Institute for Orthopaedic Research,Shenzhen People's Hospital,The First Affiliated Hospital of Southern University of Science and Technology,Jinan University Second College of Medicine,Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration,Shenzhen,518001,China
2.Department of Biology,Southern University of Science and Technology,Shenzhen,518000,China
3.Department of Medicine,Southern University of Science and Technology,Shenzhen,518000,China
4.Department of Orthopaedics and Traumatology,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong
5.Department of Biomedical Engineering,The Chinese University of Hong Kong,Hong Kong

Chen，Xin,Tan，Baoyu,Wang，Shang,et al. Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions[J]. BIOMATERIALS,2021,274.

Chen，Xin.,Tan，Baoyu.,Wang，Shang.,Tang，Rongze.,Bao，Zhiteng.,...&Peng，Songlin.(2021).Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions.BIOMATERIALS,274.

Chen，Xin,et al."Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions".BIOMATERIALS 274(2021).