Department of Organic Materials Engineering, Chungnam National University, Daejeon, South Korea.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
Acta Biomater. 2021 Mar 15;123:254-262. doi: 10.1016/j.actbio.2021.01.014. Epub 2021 Jan 16.
It was demonstrated herein that the adhesive property of catechol-functionalized nanocomposite hydrogel can be enhanced by tuning the cohesive strength due to the secondary crosslinking between catechol and synthetic bioactive nanosilicate, viz. Laponite (LP). The nanocomposite hydrogel consists of the natural anionic poly(γ-glutamic acid) (γ-PGA), which was functionalized with catechol moiety, and incorporated with disk-structured LP. The dual-crosslinked hydrogel was fabricated by enzymatic chemical crosslinking of catechol in the presence of horseradish peroxidase (HRP) and HO, and physical crosslinking between γ-PGA-catechol conjugate and LP. The PGADA/LP nanocomposite hydrogels with catechol moieties showed strong adhesiveness to various tissue layers and demonstrated an excellent hemostatic properties. These PGADA/LP nanocomposite hydrogels are potentially applied for injectable tissue engineering hydrogels, tissue adhesives, and hemostatic materials. STATEMENT OF SIGNIFICANCE: Recently, many attempts have been performed to manufacture high-performance tissue adhesives using synthetic and natural polymer-based materials. In order to apply in various biological substrates, commercially available tissue adhesives should have an improved adhesive property in wet conditions. Here, we designed a mussel-inspired dual crosslinked tissue adhesive that meets most of conditions as an ideal tissue adhesive. The designed tissue adhesive is composed of poly(γ-glutamic acid)-dopamine conjugate (PGADA)-gluing macromer, horseradish peroxidase (HRP)/hydrogen peroxide (HO)-enzymatic crosslinker, and Laponite (LP)-additional physical crosslinking nanomaterial. The PGADA hydrogel has tunable physicochemical properties by controlling the LP concentration. Furthermore, this dual crosslinked hydrogel shows strong tissue adhesive property, regardless of the tissue types. Specially the PGADA hydrogel has tissue adhesive strength four times higher than commercial bioadhesive. This dual crosslinked PGADA hydrogel with improved tissue adhesion property is a promising biological tissue adhesive for various tissue type in surgical operation.
本文研究表明，通过调节由于儿茶酚与合成生物活性纳米硅酸盐（即 Laponite（LP））之间的二次交联而产生的内聚强度，可以增强儿茶酚功能化纳米复合水凝胶的粘附性能。该纳米复合水凝胶由天然阴离子聚（γ-谷氨酸）（γ-PGA）组成，该聚（γ-谷氨酸）经儿茶酚修饰，同时掺入盘状 LP。在辣根过氧化物酶（HRP）和 HO存在下，通过酶化学交联儿茶酚制备双交联水凝胶，以及 γ-PGA-儿茶酚缀合物与 LP 之间的物理交联。具有儿茶酚部分的 PGADA/LP 纳米复合水凝胶对各种组织层表现出很强的粘附性，并表现出优异的止血性能。这些 PGADA/LP 纳米复合水凝胶有望应用于可注射组织工程水凝胶、组织粘合剂和止血材料。意义声明：最近，人们尝试使用合成和天然聚合物基材料制造高性能组织粘合剂。为了应用于各种生物基质，市售的组织粘合剂在潮湿条件下应具有更好的粘附性能。在这里，我们设计了一种受贻贝类启发的双交联组织粘合剂，它满足了作为理想组织粘合剂的大多数条件。设计的组织粘合剂由聚（γ-谷氨酸）-多巴胺缀合物（PGADA）-胶黏剂大分子、辣根过氧化物酶（HRP）/过氧化氢（HO）-酶交联剂和 Laponite（LP）-额外物理交联纳米材料组成。通过控制 LP 浓度，可以调节 PGADA 水凝胶的物理化学性质。此外，这种双交联水凝胶具有很强的组织粘合性能，与组织类型无关。特别是 PGADA 水凝胶的组织粘合强度比商业生物粘合剂高四倍。这种具有改善的组织粘附性能的双交联 PGADA 水凝胶是一种有前途的用于各种组织类型的手术的生物组织粘合剂。
