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Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix.

ABSTRACT: Patients with diabetes experience impaired growth factor production such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), and they are reportedly involved in wound healing processes. Here, we report dual growth factor-loaded hyaluronate collagen dressing (Dual-HCD) matrix, using different ratios of the concentration of stabilized growth factors-stabilized-EGF (S-EGF) and stabilized-bFGF (S-bFGF). At first, the optimal concentration ratio of S-EGF to S-bFGF in the Dual-HCD matrix is determined to be 1:2 in type I diabetic mice. This Dual-HCD matrix does not cause cytotoxicity and can be used in vivo. The wound-healing effect of this matrix is confirmed in type II diabetic mice. Dual HCD enhances angiogenesis which promotes wound healing and thus, it shows a significantly greater synergistic effect than the HCD matrix loaded with a single growth factor. Overall, we conclude that the Dual-HCD matrix represents an effective therapeutic agent for impaired diabetic wound healing.

SUBMITTER: Kim J

PROVIDER: S-EPMC7970265 | biostudies-literature | 2021 Jan-Dec

REPOSITORIES: biostudies-literature

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Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix.

Kim Jihyun J Lee Kyoung-Mi KM Han Seung Hwan SH Ko Eun Ae EA Yoon Dong Suk DS Park Ik Kyu IK Shin Hang-Cheol HC Park Kwang Hwan KH Lee Jin Woo JW

Journal of tissue engineering 20210101

Patients with diabetes experience impaired growth factor production such as epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF), and they are reportedly involved in wound healing processes. Here, we report dual growth factor-loaded hyaluronate collagen dressing (Dual-HCD) matrix, using different ratios of the concentration of stabilized growth factors-stabilized-EGF (S-EGF) and stabilized-bFGF (S-bFGF). At first, the optimal concentration ratio of S-EGF to S-bFGF in the Dual- ...[more]

PMID: 33796249

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Project description:Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal strategy to prevent abdominal adhesions. Keratinocyte growth factor (KGF) has been proven to improve the proliferation of mesothelial cells, which may enhance fibrinolytic activity to suppress postoperative adhesions. This study investigated whether the combined administration of KGF and a sodium hyaluronate (HA) gel can prevent intra-abdominal adhesions by improving the orderly repair of the peritoneal mesothelial cells. The possible prevention mechanism was also explored. The cecum wall and its opposite parietal peritoneum were abraded after laparotomy to induce intra-abdominal adhesion formation. Animals were randomly allocated to receive topical application of HA, KGF, KGF + HA, or normal saline (Control). On postoperative day 7, the adhesion score was assessed with a visual scoring system. Masson's trichrome staining, picrosirius red staining and hydroxyproline assays were used to assess the magnitude of adhesion and tissue fibrosis. Cytokeratin, a marker of the mesothelial cells, was detected by immunohistochemistry. The levels of tissue plasminogen activator (tPA), interleukin-6 (IL-6), and transforming growth factor β1 (TGF-β1) in the abdominal fluid were determined using enzyme-linked immunosorbent assays (ELISAs). Western blotting was performed to examine the expression of the TGF-β1, fibrinogen and α-smooth muscle actin (α-SMA) proteins in the rat peritoneal adhesion tissue. The combined administration of KGF and HA significantly reduced intra-abdominal adhesion formation and fibrin deposition and improved the orderly repair of the peritoneal mesothelial cells in the rat model. Furthermore, the combined administration of KGF and HA significantly increased the tPA levels but reduced the levels of IL-6, tumor necrosis factor α (TNF-α) and TGF-β1 in the abdominal fluid. The expression levels of TGF-β1, fibrinogen and α-SMA protein and mRNA in the rat peritoneum or adhesion tissues were also down-regulated following the combined administration of KGF and HA. The combined administration of KGF and HA can significantly prevent postoperative intra-abdominal adhesion formation by maintaining the separation of the injured peritoneum and promoting mesothelial cell regeneration. The potential mechanism may be associated with rapid mesothelial cell repair in the injured peritoneum. This study suggests that combined administration of KGF and HA may be a promising pharmacotherapeutic strategy for preventing abdominal adhesions, which is worth further study, and has potential value in clinical applications.

Dataset Information

Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix.

Publications

Development of stabilized dual growth factor-loaded hyaluronate collagen dressing matrix.

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