One-Step Manufacture and Crosslinking of Gelatin/Polygonum sibiricum Polysaccharide Bioactive Nanofibrous Sponges for Rapid Hemostasis and Infected Wound Healing

Abstract

The occurrence of uncontrolled hemorrhage and wound infection represents a significant cause of mortality in military and clinical settings, particularly in instances of traumatic injury. In this regard, developing an effective method to facilitate rapid hemostasis and treat infected wounds is of significant importance and value. In this study, we developed a novel strategy for the one-step manufacturing and crosslinking of gelatin (Gel)/Polygonum sibiricum polysaccharide (PSP) bioactive nanofibrous sponge through electrospinning with a homemade liquid vortex collector. Attributed to the addition of a specific ratio of tannic acid (TA) in the electrospinning solution, the resulting gelatin-tannic acid-Polygonum sibiricum polysaccharide (GelTa-PSP) nanofibrous sponges can be in-situ crosslinked during the electrospinning process and easily collected in the expected shape and size, without the need for any toxic crosslinking agent for post-treatment. We demonstrate that GelTa-PSP nanofibrous sponges possess excellent water absorption and hemostatic properties, adequate antimicrobial activity, and favorable biocompatibility. Specifically, the GelTa-PSP nanofibrous sponges encourage blood cell adhesion and exhibit strong hemostatic capabilities. In comparison to medical gauze, the GelTa-PSP nanofibrous sponges provide effective procoagulant function and hemostatic impact in rat tail-breaking and liver injury models. Moreover, due to the bioactivity of Chinese herbal medicine flavonoid polysaccharides, the GelTa-PSP nanofibrous sponges demonstrated enhanced performance in wound healing of infected rats. These findings suggest that GelTa-PSP nanofibrous sponges hold significant potential as a biomaterial for clinical applications in hemostasis and wound healing.

Schematic illustration showing the preparation of GelTa-PSP nanofibrous sponges and its application for rapid hemostasis and infected wound healing

Keywords

Polygonum sibiricum polysaccharide / Nanofibrous sponge / Hemostasis / Antibacterial / Infected wound healing

References

[1] SongYT, HuQX, LiuSH, WangYH, ZhangHG, ChenJH, YaoGT. Electrospinning/3D printing drug-loaded antibacterial polycaprolactone nanofiber/sodium alginate-gelatin hydrogel bilayer scaffold for skin wound repair. Int J Biol Macromol, 2024, 275129705

[2] YuanZC, ZhaoY, ShafiqM, SongJH, HouJ, LiangYQ, YuX, ChenYJ, YuF, El NewehyM, El HamsharyH, MorsiY, JiangSC, ZhengH, MoXM. Multi-functional fibrous dressings for burn injury treatment with pain and swelling relief and scarless wound healing. Adv Fiber Mater, 2023, 51963

[3] ChenY, WangX, TaoS, WangQ, MaPQ, LiZB, WuYL, LiDW. Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties. Mil Med Res, 2023, 1037

[4] NingXC, WangRJ, LiuN, YouY, WangYW, WangJ, WangYF, ChenZY, ZhaoHG, WuT. Three-dimensional structured PLCL/ADM bioactive aerogel for rapid repair of full-thickness skin defects. Biomater Sci, 2024, 126325

[5] WangLL, XueB, ZhangX, GaoYH, XuPP, DongB, ZhangLJ, ZhangL, LiL, LiuWZ. Extracellular matrix-mimetic intrinsic versatile coating derived from marine adhesive protein promotes diabetic wound healing through regulating the microenvironment. ACS Nano, 2024, 1814726

[6] YangY, HeG, PanZ, ZhangKW, XianYW, ZhuZR, HongYL, ZhangC, WuDC. An injectable hydrogel with ultrahigh burst pressure and innate antibacterial activity for emergency hemostasis and wound repair. Adv Mater, 2024, 36e2404811

[7] YangZH, ChenLH, LiuJ, ZhuangH, LinW, LiCL, ZhaoXJ. Short peptide nanofiber biomaterials ameliorate local hemostatic capacity of surgical materials and intraoperative hemostatic applications in clinics. Adv Mater, 2023, 352301849

[8] TanY, YangQ, ZhengM, SarwarMT, YangHM. Multifunctional nanoclay-based hemostatic materials for wound healing: a review. Adv Healthc Mater, 2024, 132302700

[9] PengHT. Hemostatic agents for prehospital hemorrhage control: a narrative review. Mil Med Res, 2020, 713

[10] KharazihaM, ScheibelT, SalehiS. Multifunctional naturally derived bioadhesives: from strategic molecular design toward advanced biomedical applications. Prog Polym Sci, 2024, 150101792

[11] NepalA, TranHDN, NguyenN-T, TaHT. Advances in haemostatic sponges: characteristics and the underlying mechanisms for rapid haemostasis. Bioact Mater, 2023, 27231

[12] SezerUA, KocerZ, SahinI, AruB, DemirelGY, SezerS. Oxidized regenerated cellulose cross-linked gelatin microparticles for rapid and biocompatible hemostasis: a versatile cross-linking agent. Carbohydr Polym, 2018, 200624

[13] HuangZ, AnH, GuoHT, JiS, GuQ, GuZ, WenYQ. An asymmetric natural nanofiber with rapid temperature responsive detachability inspired by Andrias davidianus for full-thickness skin wound healing. Adv Fiber Mater, 2024, 6473

[14] LiBR, LiHF, ChenHJ, LiuY, ChenJL, FengQ, CaoXD, DongH. Microgel assembly powder improves acute hemostasis, antibacterial, and wound healing via in situ co-assembly of erythrocyte and microgel. Adv Funct Mater, 2023, 332302793

[15] WangHH, WangMX, WuJH, ZhuSL, YeYN, LiuYS, LiK, LiRY, ZhangYH, WeiM, YangX, MengLX. Nature-inspired gelatin-based adhesive hydrogel: a rapid and user-friendly solution for hemostatic applications. Adv Healthc Mater, 2024, 132304444

[16] ZhuY, ZhangLN, DuanWL, Martin-SaldanaS, LiCW, YuHW, FengLY, ZhangXP, DuBJ, LiGJ, ZhengXF, BuYZ. Succinic ester-based shape memory gelatin sponge for noncompressible hemorrhage without hindering tissue regeneration. Adv Healthc Mater, 2023, 122202122

[17] XieXR, LiD, ChenYJ, ShenYH, YuF, WangW, YuanZC, MorsiY, WuJL, MoXM. Conjugate electrospun 3D gelatin nanofiber sponge for rapid hemostasis. Adv Healthc Mater, 2021, 102100918

[18] HerlianaH, YusufHY, LavianaA, WandawaG, AbbasB. In vitro hemostatic activity of novel fish gelatin–alginate sponge (FGAS) prototype. Polymers, 2024, 162047

[19] ZhangQ, QiaoYS, ZhuJH, LiYM, LiCJ, LinJ, LiXL, HanH, MaoJF, WangFJ, WangL. Electroactive and antibacterial surgical sutures based on chitosan-gelatin/tannic acid/polypyrrole composite coating. Compos B, 2021, 223109140

[20] YinXJ, RenJL, LanW, ChenY, OuyangMP, SuH, ZhangLB, ZhuJT, ZhangC. Microfluidics-assisted optimization of highly adhesive haemostatic hydrogel coating for arterial puncture. Bioact Mater, 2022, 12133

[21] ZhouL, FanL, YiX, ZhouZN, LiuC, FuRM, DaiC, WangZG, ChenXX, YuP, ChenDF, TanGX, WangQY, NingCY. Soft conducting polymer hydrogels cross-linked and doped by tannic acid for spinal cord injury repair. ACS Nano, 2018, 1210957

[22] LameiE, HasanzadehM. Fabrication of chitosan nanofibrous scaffolds based on tannic acid and metal-organic frameworks for hemostatic wound dressing applications. Int J Biol Macromol, 2022, 208409

[23] OsaliS, GhiyasiY, EsfahaniH, JoseR, RamakrishnaS. Electrospun nanomembranes at the liquid–liquid and solid–liquid interface—a review. Mater Today, 2023, 67151

[24] ShiS, SiYF, HanYT, WuT, IqbalMI, FeiB, LiRKY, HuJL, QuJP. Recent progress in protective membranes fabricated via electrospinning: advanced materials, biomimetic structures, and functional applications. Adv Mater, 2022, 342107938

[25] WeigelT, MalkmusC, WeigelV, WussmannM, BergerC, BrenneckeJ, Groeber-BeckerF, HansmannJ. Fully synthetic 3D fibrous scaffolds for stromal tissues-replacement of animal-derived scaffold materials demonstrated by multilayered skin. Adv Mater, 2022, 342106780

[26] ChenYJ, DongXT, ShafiqM, MylesG, RadacsiN, MoXM. Recent advancements on three-dimensional electrospun nanofiber scaffolds for tissue engineering. Adv Fiber Mater, 2022, 4959

[27] ChenYJ, ShafiqM, LiuMY, MorsiY, MoXM. Advanced fabrication for electrospun three-dimensional nanofiber aerogels and scaffolds. Bioact Mater, 2020, 5963

[28] YuanJY, SunBB, MaWX, CaiC, HuangZZ, ZhouPY, YiL, LiuLB, ChenSX. Orthogonally woven 3D nanofiber scaffolds promote rapid soft tissue regeneration by enhancing bidirectional cell migration. Bioact Mater, 2024, 39582

[29] HuangZH, WangDH, SonderskovSM, XiaD, WuXT, LiangCY, DongMD. Tannic acid-functionalized 3D porous nanofiber sponge for antibiotic-free wound healing with enhanced hemostasis, antibacterial, and antioxidant properties. Nanobiotechnol, 2023, 21190

[30] ZhangKL, BhuttoMA, WangLY, WangK, LiuJ, LiWY, CuiWG, FuQ. Double-layer nanofibrous sponge tube via electrospun fiber and yarn for promoting urethral regeneration. Adv Fiber Mater, 2023, 5662

[31] ZongDD, ZhangXX, YinX, WangF, YuJY, ZhangSC, DingB. Electrospun fibrous sponges: principle, fabrication, and applications. Adv Fiber Mater, 2022, 41434

[32] ZhangXM, LiuKJ, QinM, LanWW, WangLF, LiangZW, LiXC, WeiY, HuYC, ZhaoLQ, LianXJ, HuangD. Abundant tannic acid modified gelatin/sodium alginate biocomposite hydrogels with high toughness, antifreezing, antioxidant and antibacterial properties. Carbohydr Polym, 2023, 309120702

[33] HanH, TangLQ, LiY, LiY, BiM, WangJ, WangFJ, WangL, MaoJF. A multifunctional surgical suture with electroactivity assisted by oligochitosan/gelatin-tannic acid for promoting skin wound healing and controlling scar proliferation. Carbohydr Polym, 2023, 320121236

[34] YangG, WangCR, WangYP, LiuXQ, ZhangY, XuM, DengHZ, WangWW. Noncovalent co-assembly of aminoglycoside antibiotics@tannic acid nanoparticles for off-the-shelf treatment of pulmonary and cutaneous infections. Chem Eng J, 2023, 474145703

[35] XiaoLF, LiuHF, HuangHY, WuSJ, XueLJ, GengZ, CaiL, YanFF. 3D nanofiber scaffolds from 2D electrospun membranes boost cell penetration and positive host response for regenerative medicine. Nanobiotechnol, 2024, 22322

[36] SharmaA, VermaC, MukhopadhyayS, GuptaA, GuptaB. Development of sodium alginate/glycerol/tannic acid coated cotton as antimicrobial system. Int J Biol Macromol, 2022, 216303

[37] WangRN, LiRY, ZhengP, YangZC, QianC, WangZ, QianSH. Silver nanoparticles modified with Polygonatum sibiricum Polysaccharide improve biocompatibility and infected wound bacteriostasis. Microbiol, 2023, 61543

[38] CaoHK, XiangD, ZhouX, YuePP, ZouYK, ZhongZB, MaYS, WangLZ, WuSQ, YeQF. High-strength, antibacterial, antioxidant, hemostatic, and biocompatible chitin/PEGDE-tannic acid hydrogels for wound healing. Carbohydr Polym, 2023, 307120609

[39] ZhouZB, XiaoJW, GuanSW, GengZJ, ZhaoRF, GaoBT. A hydrogen-bonded antibacterial curdlan-tannic acid hydrogel with an antioxidant and hemostatic function for wound healing. Carbohydr Polym, 2022, 285119235

[40] WangSQ, LiG, ZhangXF, WangYQ, QiangY, WangBL, ZouJB, NiuJF, WangZZ. Structural characterization and antioxidant activity of Polygonatum sibiricum polysaccharides. Carbohydr Polym, 2022, 291119524

[41] LiuN, ZhouZY, NingXC, ZhangXP, GuoQX, GuoMX, WangYF, WuT. Enhancing the paracrine effects of adipose stem cells using nanofiber- based meshes prepared by light-welding for accelerating wound healing. Mater Des, 2023, 225111582

[42] GuoAJ, LiXY, PanLH, LiQM, LuoJP, ZhaXQ. The interventional effect of Polygonatum cyrtonema Hua polysaccharide on atherosclerosis in mice of different sexes. Food Sci Hum Wellness, 2024, 13370

[43] XuXR, ShanMM, ChuCQ, BieSK, WangH, CaiSB. Polysaccharides from Polygonatum kingianum Collett & Hemsl ameliorated fatigue by regulating NRF2/HO-1/NQO1 and AMPK/PGC-1α/TFAM α /TFAM signaling pathways, and gut microbiota. Int J Biol Macromol, 2024, 266131440

[44] ZhaoYD, YiBC, HuJL, ZhangDJ, LiGT, LuY, ZhouQH. Double cross-linked biomimetic hyaluronic acid-based hydrogels with thermo-stimulated self-contraction and tissue adhesiveness for accelerating post-wound closure and wound healing. Adv Funct Mater, 2023, 332300710

[45] OmidianH, AkhzarmehrA, ChowdhurySD. Advancements in cellulose-based superabsorbent hydrogels: sustainable solutions across industries. Gels, 2024, 10174

[46] TithyLH, RahmanA, WongSY, LiX, ArafatMT. Chitosan/starch based unoxidized tannic acid modified microparticles for rapid hemostasis with broad spectrum antibacterial activity. Carbohydr Polym, 2024, 336122111

[47] NatarajanV, KrithicaN, MadhanB, SehgalPK. Preparation and properties of tannic acid cross-linked collagen scaffold and its application in wound healing. Biomed Mater Res, 2013, 101B560

[48] BlakeneyBA, TambralliA, AndersonJM, AndukuriA, LimDJ, DeanDR, JunHW. Cell infiltration and growth in a low density, uncompressed three-dimensional electrospun nanofibrous scaffold. Biomaterials, 2011, 321583

Funding

Taishan Scholar Foundation of Shandong Province(No. tsqn202211125)

Natural Science Foundation of Shandong Province(ZR2024JQ026)

National Natural Science Foundation of China(82001970)

Young Elite Scientists Sponsorship Program by CAST(No. YESS20200097)

Qingdao Clinical Research Center for Oral Diseases(22-3-7-lczx-7-nsh)

Qingdao Key Health Discipline Development Fund(2025-2027)

Shandong Provincial Key Medical and Health Discipline of Oral Medicine(2025-2027)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China