2. Academic Validation
  3. Construction of anti-calcification small-diameter vascular grafts using decellularized extracellular matrix/poly (L-lactide-co-ε-caprolactone) and baicalin-cathepsin S inhibitor

Construction of anti-calcification small-diameter vascular grafts using decellularized extracellular matrix/poly (L-lactide-co-ε-caprolactone) and baicalin-cathepsin S inhibitor

  • Acta Biomater. 2025 May 1:197:184-201. doi: 10.1016/j.actbio.2025.03.033.
Yanjiao Teng 1,  Xiaohai Zhang 2,  Lin Song 2,  Jianing Yang 1,  Duo Li 1,  Ziqi Shi 1,  Xiaoqin Guo 1,  Shufang Wang 3,  Haojun Fan 1,  Li Jiang 4,  Shike Hou 5,  Seeram Ramakrishna 6,  Qi Lv 7,  Jie Shi 8
Affiliations

Affiliations

  • 1 School of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, PR China; Key Laboratory for Disaster Medicine Technology, Tianjin 300072, PR China; Wenzhou Safety (Emergency) Institute of Tianjin University, Wenzhou 325026, PR China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210000, PR China.
  • 3 Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, PR China.
  • 4 Tianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Tianjin 300021, PR China.
  • 5 School of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, PR China; Key Laboratory for Disaster Medicine Technology, Tianjin 300072, PR China; Wenzhou Safety (Emergency) Institute of Tianjin University, Wenzhou 325026, PR China. Electronic address: housk86@163.com.
  • 6 Department of Mechanical Engineering, College of Design and Engineering, National University of Singapore, Singapore 117575, Singapore. Electronic address: seeram@nus.edu.sg.
  • 7 School of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, PR China; Key Laboratory for Disaster Medicine Technology, Tianjin 300072, PR China; Wenzhou Safety (Emergency) Institute of Tianjin University, Wenzhou 325026, PR China. Electronic address: lvqi68@163.com.
  • 8 School of Disaster and Emergency Medicine, Tianjin University, Tianjin 300072, PR China; Key Laboratory for Disaster Medicine Technology, Tianjin 300072, PR China; Wenzhou Safety (Emergency) Institute of Tianjin University, Wenzhou 325026, PR China. Electronic address: jie.shi@tju.edu.cn.
PMID: 40120837 DOI: 10.1016/j.actbio.2025.03.033
Abstract

The long-term transplantation of small-diameter vascular grafts (SDVGs) is associated with a risk of calcification, which is a key factor limiting the clinical translation of SDVG. Hence, there is an urgency attached to the development of new SDVGs with anti-calcification properties. Here, we used decellularized extracellular matrix (dECM) and poly (L-lactide-co-ε-caprolactone) (PLCL) as base Materials and combined these with baicalin, Cathepsin S (Cat S) inhibitor to prepare PBC-SDVGs by electrospinning. Baicalin contains carboxyl and hydroxyl groups that can interact with chemical groups in dECM powder, potentially blocking calcium nucleation sites. Cat S inhibitor prevents elastin degradation and further reduces the risk of calcification. PBC-SDVGs were biocompatible and when implanted in rat abdominal aorta, accelerated endothelialization, enhanced vascular tissue regeneration, inhibited elastin degradation, and promoted macrophage polarization M2 phenotype to regulate inflammation. After 3 months of implantation, the results of Doppler ultrasound, MicroCT, and histological staining revealed a significant reduction in calcification. In summary, the developed anti-calcification SDVGs offer a promising strategy for long-term implantation with significant clinical application potential. STATEMENT OF SIGNIFICANCE: The dECM and PLCL were used as base Materials, connected with baicalin, and loaded with Cat S inhibitor to prepare PBC-SDVGs. The baicalin and dECM powder formed hydrogen bonds to crosslink together reducing the calcium deposition. In vitro, the vascular graft downregulated the expression level of osteogenic genes and promoted macrophage polarization toward an anti-inflammatory M2 phenotype, thereby reducing calcification. The PBC-SDVGs implanted in rat abdominal aorta can accelerate endothelialization, enhance vascular tissue regeneration, inhibit elastin degradation, reduce inflammation response and calcification.

Keywords

Anti-calcification, tissue regeneration; Baicalin; Cathepsin S inhibitor; Small-diameter vascular grafts.

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