Fast-curing resilin bioshield with tailored stiffness and bioactivity for guided bone regeneration

Yusai Zhou^{¹^,⁴^,^§}, Yajuan Xie^{²^,³^,^§}, Yunfan Zhang^{³^,⁵^,^§}, Xiaomo Liu^{²^,³^,^§}, Bo Li^⁴, Bing Han^{²^,³}

(), Ruichu Zhang^{²^,³}, Chaonan Jin^⁴, Yao Sun^⁴, Chao Ma^{⁴^,⁷}, Shengxue Yang^¹, Li Miao^⁶

(), Hongjie Zhang^{⁴^,⁷}, Kai Liu^{⁴^,⁷}

(), Yan Wei^{³^,⁵}

()

1School of Materials Science and Engineering, Beihang University, Beijing 100191, China

2Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China

3National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing 100081, China

4Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China

5Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing 100081, China

6Department of Stomatology, the 7th Medical Center, Chinese PLA General Hospital, Beijing 100700, China

7Xiangfu Laboratory, Jiaxing 314102, China

^§ Yusai Zhou, Yajuan Xie, Yunfan Zhang, and Xiaomo Liu contributed equally to this work.

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We presented a fast-curing approach to engineer recombinant resilin bioshield with tunable modulus, superior bioactivity, and rapid assembly kinetics. The mineralized bioshield demonstrated robust barrier functionality and the capacity to orchestrate cellular behavior, significantly accelerating bone regeneration in vivo.

Abstract

Severe bone defects pose a formidable clinical challenge in orthopedics, urgently demanding the development of advanced biomaterials to restore structural and functional integrity. While current regenerative materials, such as collagen-containing products, demonstrate a certain degree of biocompatibility, they are still hampered by limitations that include poor mechanical performance, restricted barrier effects, and arduous preparation methods. Here, we report a rapid-curing methodology to engineer recombinant resilin bioshield with tunable modulus, superior bioactivity, and rapid assembly kinetics. The resilin bioshield is rapidly formed within minutes via a tyrosine-mediated photo-crosslinking strategy, achieving spatially programmable assembly. Enzymatic integration of alkaline phosphatase into the resilin matrix drives in situ mineralization, yielding densely packed hydroxyapatite (HAP) nanocrystals. Remarkably, this process enables controlled modulus tuning of the bioshield across three orders of magnitude, achieving an exceptional maximum modulus of 145 MPa while retaining excellent flexibility, thus surpassing conventional guided bone regeneration materials. Beyond its mechanical superiority, the mineralized resilin bioshield not only directs cellular behavior by enhancing adhesion and spreading but also robustly drives the osteogenic differentiation of mesenchymal stem cells, thereby accelerating functional bone regeneration. As a result, our work provides an alternative approach for creating high-performance barrier membranes for guided bone regeneration.

Keywords

resilin mineralization mechanical performance barrier membrane guided bone regeneration

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References

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