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Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration.

ABSTRACT: Abdominal wall defect caused by open abdomen (OA) or abdominal trauma is a serious issue since it induces several clinical problems. Although a variety of prosthetic materials are commonly employed, complications occur including host soft tissue response, fistula formation and chronic patient discomfort. Recently, abundant natural polymers have been used for injectable hydrogel synthesis in tissue regeneration. In this study, we produced the chitosan - hyaluronic acid (CS/HA) hydrogel and investigated its effects on abdominal tissue regeneration. The physical and biological properties of the hydrogel were demonstrated to be suitable for application in abdominal wounds. In a rat model simulating open abdomen and large abdominal wall defect, rapid cellular response, sufficient ECM deposition and marked neovascularization were found after the application of the hydrogel, compared to the control group and fibrin gel group. Further, the possible mechanism of these findings was studied. Cytokines involved in angiogenesis and cellular response were increased and the skew toward M2 macrophages credited with the functions of anti-inflammation and tissue repair was showed in CS/HA hydrogel group. These findings suggested that CS/HA hydrogel could prevent the complications and was promising for abdominal tissue regeneration.

SUBMITTER: Deng Y

PROVIDER: S-EPMC5457437 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration.

Deng Youming Y Ren Jianan J Chen Guopu G Li Guanwei G Wu Xiuwen X Wang Gefei G Gu Guosheng G Li Jieshou J

Scientific reports 20170602 1

Abdominal wall defect caused by open abdomen (OA) or abdominal trauma is a serious issue since it induces several clinical problems. Although a variety of prosthetic materials are commonly employed, complications occur including host soft tissue response, fistula formation and chronic patient discomfort. Recently, abundant natural polymers have been used for injectable hydrogel synthesis in tissue regeneration. In this study, we produced the chitosan - hyaluronic acid (CS/HA) hydrogel and invest ...[more]

PMID: 28578386

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Project description:Rationale: Injectable matrices are highly desirable for stem cell delivery. Previous research has highlighted the benefit of scaffold macroporosity in enhancing stem cell survival and bone regeneration in vivo. However, there remains a lack of injectable and in situ crosslinkable macroporous matrices for stem cell delivery to achieve fast bone regeneration in immunocompetent animal model. The goal of this study is to develop an injectable gelatin-based μRB hydrogel supporting direct cell encapsulation that is available in clinics as macroporous matrices to enhance adipose-derived stromal cell (ASC) survival, engraftment and accelerate bone formation in craniofacial defect mouse. Methods: Injectable and in situ crosslinkable gelatin microribbon (μRB)-based macroporous hydrogels were developed by wet-spinning. Injectability was optimized by varying concentration of glutaraldehyde for intracrosslinking of μRB shape, and fibrinogen coating. The efficacy of injectable μRBs to support ASCs delivery and bone regeneration were further assessed in vivo using an immunocompetent mouse cranial defect model. ASCs survival was evaluated by bioluminescent imaging and bone regeneration was assessed by micro-CT. The degradation and biocompatibility were determined by histological analysis. Results: We first optimized injectability by varying concentration of glutaraldehyde used to fix gelatin μRBs. The injectable μRB formulation were subsequently coated with fibrinogen, which allows in situ crosslinking by thrombin. Fluorescence imaging and histology showed majority of μRBs degraded by the end of 3 weeks. Injectable μRBs supported comparable level of ASC proliferation and bone regeneration as implantable prefabricated μRB controls. Adding low dosage of BMP2 (100 ng per scaffold) with ASCs substantially accelerated the speed of mineralized bone regeneration, with 90% of the bone defect refilled by week 8. Immunostaining showed M1 (pro-inflammatory) macrophages were recruited to the defect at day 3, and was replaced by M2 (anti-inflammatory) macrophages by week 2. Adding μRBs or BMP2 did not alter macrophage response. Injectable µRBs supported vascularization, and BMP-2 further enhanced vascularization. Conclusions: Our results demonstrated that µRB-based scaffolds enhanced ASC survival and accelerated bone regeneration after injection into critical sized cranial defect mouse. Such injectable µRB-based scaffold can provide a versatile biomaterial for delivering various stem cell types and enhancing tissue regeneration.

Project description:Injury caused by trauma, burns, surgery, or disease often results in soft tissue loss leading to impaired function and permanent disfiguration. Tissue engineering aims to overcome the lack of viable donor tissue by fabricating synthetic scaffolds with the requisite properties and bioactive cues to regenerate these tissues. Biomaterial scaffolds designed to match soft tissue modulus and strength should also retain the elastomeric and fatigue-resistant properties of the tissue. Of particular design importance is the interconnected porous structure of the scaffold needed to support tissue growth by facilitating mass transport. Adequate mass transport is especially true for newly implanted scaffolds that lack vasculature to provide nutrient flux. Common scaffold fabrication strategies often utilize toxic solvents and high temperatures or pressures to achieve the desired porosity. In this study, a polymerized medium internal phase emulsion (polyMIPE) is used to generate an injectable graft that cures to a porous foam at body temperature without toxic solvents. These poly(ester urethane urea) scaffolds possess elastomeric properties with tunable compressive moduli (20-200 kPa) and strengths (4-60 kPa) as well as high recovery after the first conditioning cycle (97-99%). The resultant pore architecture was highly interconnected with large voids (0.5-2 mm) from carbon dioxide generation surrounded by water-templated pores (50-300 ?m). The ability to modulate both scaffold pore architecture and mechanical properties by altering emulsion chemistry was demonstrated. Permeability and form factor were experimentally measured to determine the effects of polyMIPE composition on pore interconnectivity. Finally, initial human mesenchymal stem cell (hMSC) cytocompatibility testing supported the use of these candidate scaffolds in regenerative applications. Overall, these injectable polyMIPE foams show strong promise as a biomaterial scaffold for soft tissue repair.

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Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration.

Publications

Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration.

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