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  2. Sulfated glycosaminoglycans in decellularized placenta matrix as critical regulators for cutaneous wound healing

Sulfated glycosaminoglycans in decellularized placenta matrix as critical regulators for cutaneous wound healing

  • Acta Biomater. 2021 Mar 1;122:199-210. doi: 10.1016/j.actbio.2020.12.055.
Chen Wang 1 Guoyun Li 2 Kaige Cui 3 Zihan Chai 3 Ziyu Huang 3 Yue Liu 3 Shang Chen 3 Haoyan Huang 3 Kaiyue Zhang 3 Zhibo Han 4 Yuhao Li 3 Guangli Yu 2 Zhong-Chao Han 4 Na Liu 5 Zongjin Li 6
Affiliations

Affiliations

  • 1 Nankai University School of Medicine, Tianjin 300071, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin 300071, China.
  • 2 School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
  • 3 Nankai University School of Medicine, Tianjin 300071, China.
  • 4 Jiangxi Engineering Research Center for Stem Cell, Shangrao 334109, Jiangxi, China; Tianjin Key Laboratory of Engineering Technologies for Cell Pharmaceutical, National Engineering Research Center of Cell Products, AmCellGene Co., Ltd., Tianjin 300457, China; Beijing Engineering Laboratory of Perinatal Stem Cells, Beijing Institute of Health and Stem Cells, Health & Biotech Co., Beijing 100176, China.
  • 5 Nankai University School of Medicine, Tianjin 300071, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin 300071, China. Electronic address: liuna@nankai.edu.cn.
  • 6 Nankai University School of Medicine, Tianjin 300071, China; The Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, the College of Life Sciences, Tianjin 300071, China; State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing 100039, China; Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang 453003, China. Electronic address: zongjinli@nankai.edu.cn.
Abstract

Perinatal-related tissues, such as the placenta, umbilical cord, and amniotic membrane, are generally discarded after delivery and are increasingly attracting attention as alternative sources for decellularized extracellular matrix (dECM) isolation. Recent studies indicate that glycosaminoglycans (GAGs) in the dECM play key roles during tissue regeneration. However, the dECM is organ specific, and the glycosaminoglycanomics of dECMs from perinatal tissues and the regulatory function of GAGs have been poorly investigated. In this study, we explored the glycosaminoglycanomics of dECMs from the placenta, umbilical cord and amniotic membrane. We hypothesized that the therapeutic effects of dECMs are related to the detailed composition of GAGs. Hydrogels of dECM derived from perinatal tissues were generated, and glycosaminoglycanomics analysis was employed to identify the cues that promote tissue repair and regeneration in a murine cutaneous wound-healing model. We utilized highly sensitive liquid chromatography-tandem mass spectrometry for glycosaminoglycanomics analysis. Our results revealed that placenta-derived dECM (PL-dECM) hydrogel has higher contents of chondroitin sulfate (CS) and heparan sulfate (HS). In addition, molecular imaging showed that the PL-dECM hydrogel exerted the best anti-inflammatory and proangiogenic effects in the skin wound healing model. Further in vitro analyses demonstrated that CS with 6-O-sulfo group (CS-6S) has an anti-inflammatory effect, while HS with 6-O-sulfo group (HS-6S) plays a crucial role in angiogenesis. In conclusion, this study highlights the critical roles of GAGs in perinatal tissue-derived dECMs by promoting angiogenesis and inhibiting inflammation and indicates that it is feasible to utilize 6-sulfated GAG-enriched placental dECM hydrogel as an attractive candidate for tissue engineering and drug delivery.

Keywords

Angiogenesis; Extracellular matrix (ECM); Glycosaminoglycans; Hydrogel; Inflammation; Perinatal tissues.

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