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Scarless Wound Closure by a Mussel-Inspired Poly(amidoamine) Tissue Adhesive with Tunable Degradability.

ABSTRACT: Burn, trauma, and various medical conditions including bacterial infection, diabetes complication, and surgery could lead to an acute cutaneous wound and scar formation. Application of tissue glues instead of sutures could minimize the additional trauma and scar formation. Despite the countless efforts devoted to the development of high-strength tissue glues, little attention has been paid to their influence on the scar formation. Here, we report the development of a new tissue glue with excellent biocompatibility and tunable degradability for scarless wound closure. A series of catechol-containing poly(amidoamine) (CPAA) polymers were synthesized via the one-step Michael addition of dopamine and bisacrylamide. The tertiary amino group in the polymer backbone was used to introduce a zwitterionic sulfobetaine group by one-step ring-opening polymerization. The introduction of the zwitterionic sulfobetaine group could easily tune the hydrophilicity and the degradability of CPAA without influencing the density of the catechol group in the polymer. Lap-shear tests on the porcine skin demonstrated a high adhesion strength of 7 kPa at 1 h, rising to 24 kPa by 12 h. Addition of silica nanoparticles could further enhance the adhesion strength by 50%. In vivo studies further confirmed that the CPAA tissue glue could effectively accelerate the healing process of incisional wounds on the back of Sprague Dawley rats compared with suture and reduce the scar formation.

SUBMITTER: Peng B

PROVIDER: S-EPMC6044989 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The revolutionary role of tissue adhesives in wound closure, tissue sealing, and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing. In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators (exemplified by sodium periodate and silver nitrate), herein, the natural polyphenolic compound tannic acid (TA) was used to achieve near instantaneous (<25s), hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant, anti-inflammatory, and antimicrobial activities (3A-TCMBAs). The resulting materials were self-healing and possessed low swelling ratios (<60%) as well as considerable mechanical strength (up to ∼1.0 MPa), elasticity (elongation ∼2700%), and adhesion (up to 40 kPa). The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability, favorable cytocompatibility and cell migration, as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli (>90% bacterial death upon near-infrared (NIR) irradiation). In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs + NIR treatment could promote wound closure and collagen deposition and improve the collagen I/III ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines. Further, phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation & remodeling of the extracellular matrix (ECM) in the late stage (supported by phased CD31 (platelet endothelial cell adhesion molecule-1) PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor) expression as well as elevated matrix metalloprotein-9 (MMP-9) expression on day 21), resulting in scarless wound healing. The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant, new class of bioadhesive.

Project description:The combination of multiple physiological (swelling, porosity, mechanical, and biodegradation) and biological (cell/tissue-adhesive, cell proliferation, and hemostatic) properties on a single hydrogel has great potential for skin tissue engineering. Adhesive hydrogels based on polydopamine (PDA) have become the most popular in the biomedical field; however, integrating multiple properties on a single adhesive hydrogel remains a challenge. Here, inspired by the chemistry of mussels, we developed PDA-sodium alginate-polyacrylamide (PDA-SA-PAM)-based hydrogels with multiple physiological and biological properties for skin tissue engineering applications. The hydrogels were prepared by alkali-induced polymerization of DA followed by complexation with SA in PAM networks. The chemical composition of the hydrogels was characterized by X-ray photoelectron spectroscopy. PDA-SA complexed chains were homogeneously dispersed in the PAM network and exhibited good elasticity and excellent mechanical properties, such as a compressive stress of 0.24 MPa at a compression strain of 70% for 0.4PDA-SA-PAM. The adhesive hydrogel also maintained a highly interconnected porous structure (∼94% porosity) along with PDA microfibrils. The hydrogel possesses outstanding swelling and biodegradability properties. Owing to the presence of the PDA-SA complex in the PAM network, the hydrogels show good adhesion to various substrates (plastic, skin, glass, computer screens, and leaves); for example, the adhesive strength of the 0.4PDA-SA-PAM to porcine skin was 24.5 kPa. The adhesive component of the PDA-SA chains in the PAM network significantly improves the cell proliferation, cell attachment, cell spreading, and functional expression of human skin fibroblasts (CCD-986sk) and keratinocytes. Moreover, the PDA chains exhibited good hemostatic properties, resulting in rapid blood coagulation. Considering their excellent cell affinity, and rapid blood coagulation ability, these mussel-inspired hydrogels have substantial potential for skin tissue engineering applications.

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Scarless Wound Closure by a Mussel-Inspired Poly(amidoamine) Tissue Adhesive with Tunable Degradability.

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