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A Bioinspired Alginate-Gum Arabic Hydrogel with Micro-/Nanoscale Structures for Controlled Drug Release in Chronic Wound Healing.

ABSTRACT: Biopolymeric hydrogels have drawn increasing research interest in biomaterials due to their tunable physical and chemical properties for both creating bioactive cellular microenvironment and serving as sustainable therapeutic reagents. Inspired by a naturally occurring hydrogel secreted from the carnivorous Sundew plant for trapping insects, here we have developed a bioinspired hydrogel to deliver mitsugumin 53 (MG53), an important protein in cell membrane repair, for chronic wound healing. Both chemical compositions and micro-/nanomorphological properties inherent from the natural Sundew hydrogel were mimicked using sodium alginate and gum arabic with calcium ion-mediated cross-linking. On the basis of atomic force microscopy (AFM) force measurements, an optimal sticky hydrogel scaffold was obtained through orthogonal experimental design. Imaging and mechanical analysis showed the distinct correlation between structural morphology, adhesion characteristics, and mechanical properties of the Sundew-inspired hydrogel. Combined characterization and biochemistry techniques were utilized to uncover the underlying molecular composition involved in the interactions between hydrogel and protein. In vitro drug release experiments confirmed that the Sundew-inspired hydrogel had a biphasic-kinetics release, which can facilitate both fast delivery of MG53 for improving the reepithelization process of the wounds and sustained release of the protein for treating chronic wounds. In vivo experiments showed that the Sundew-inspired hydrogel encapsulating with rhMG53 could facilitate dermal wound healing in mouse model. Together, these studies confirmed that the Sundew-inspired hydrogel has both tunable micro-/nanostructures and physicochemical properties, which enable it as a delivery vehicle for chronic wounding healing. The research may provide a new way to develop biocompatible and tunable biomaterials for sustainable drug release to meet the needs of biological activities.

SUBMITTER: Li M

PROVIDER: S-EPMC5979260 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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A Bioinspired Alginate-Gum Arabic Hydrogel with Micro-/Nanoscale Structures for Controlled Drug Release in Chronic Wound Healing.

Li Mi M Li Haichang H Li Xiangguang X Zhu Hua H Xu Zihui Z Liu Lianqing L Liu Lianqing L Ma Jianjie J Zhang Mingjun M

ACS applied materials & interfaces 20170629 27

Biopolymeric hydrogels have drawn increasing research interest in biomaterials due to their tunable physical and chemical properties for both creating bioactive cellular microenvironment and serving as sustainable therapeutic reagents. Inspired by a naturally occurring hydrogel secreted from the carnivorous Sundew plant for trapping insects, here we have developed a bioinspired hydrogel to deliver mitsugumin 53 (MG53), an important protein in cell membrane repair, for chronic wound healing. Both ...[more]

PMID: 28640580

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Project description:BackgroundThe secretomes of mesenchymal stem cells (MSCs) have great therapeutic potential and thereby their efficient delivery into the target site is of particular interest. Here, we propose a new strategy of hMSCs-derived secretomes delivery for advanced wound healing upon harnessing the working principle of extracellular matrix (ECM)-growth factors interaction in vivo.MethodsWe prepared an alginate hydrogel based wound patch, where it contains both human MSC-derived secretomes and ECM. The ECM was obtained from the decellularization of in vitro cultured human lung fibroblasts. The alginate solution was blended with ECM suspension, crosslinked, air-dried, then rehydrated with the secretomes contained in the concentrated conditioned media (CCM) as a highly saturated form of conditioned media (CM). We tested four different groups, with or without the ECM to investigate not only the role of ECM but the therapeutic effect of secretomes.ResultsThe secretomes reserved many, diverse bioactive factors, such as VEGF, HGF, IGFBPs, IL-6, and IL-8. Alginate/ECM/CCM (AEC) patch could hold significantly larger amount of secretomes and release them longer than the other groups. Our AEC patch was the most effective in stimulating not only cell migration and proliferation but the collagen synthesis of dermal fibroblasts in vitro. Moreover, the AEC patch-treated full-thickness skin wounds disclosed significantly better wound healing indications: cell recruitment, neovascularization, epidermis thickness, keratinocyte migration, and mature collagen deposition, as assessed via histology (H&E, Herovici staining) and immunofluorescence, respectively. In particular, our AEC patch enabled a phenotype shift of myofibroblast into fibroblast over time and led to mature blood vessel formation at 14 day.ConclusionsWe believe that ECM certainly contributed to generate a secretomes-enriched milieu via ECM-secretomes interactions and thereby such secretomes could be delivered more efficiently, exerting significant therapeutic impact either individually or collectively during wound healing process.

Dataset Information

A Bioinspired Alginate-Gum Arabic Hydrogel with Micro-/Nanoscale Structures for Controlled Drug Release in Chronic Wound Healing.

Publications

A Bioinspired Alginate-Gum Arabic Hydrogel with Micro-/Nanoscale Structures for Controlled Drug Release in Chronic Wound Healing.

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