Materials · 4 authors, 2 centres
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This review summarizes recent advances in nanocellulose (NC) hydrogels for wound dressing, tissue engineering, and drug delivery, highlighting that over 60% of NC research in 2022 focused on medical applications. NCs offer tunable mechanical and biological properties, with bacterial nanocellulose showing no cytotoxicity even at high concentrations (1000 µg/mL). Key challenges include scaling production and understanding long-term in vivo interactions.
**Background:** Nanocelluloses (NCs) are sustainable nanomaterials derived from cellulose, classified into cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). Their unique properties—biocompatibility, low cytotoxicity, high mechanical strength, and tunable surface chemistry—make them attractive for biomedical applications. Between 2020 and 2022, over 50% of all NC publications were published, with more than 77% of those focusing on tissue engineering (TE), drug delivery (DD), and wound dressing (WD). In 2022 alone, over 60% of NC research was in the medical field. This review covers studies from the last three years, emphasizing NC-based hydrogels for TE, DD, and WD.
**Methods:** The authors conducted a systematic literature search in the Web of Science (WOS) database using keywords "nanocellulose," "tissue engineering," "drug delivery," and "wound dressing." From 5018 total NC publications (2020–2022), they identified 1632 for TE, 1523 for DD, and 721 for WD. After vetting for relevance, impact factor, and citation analysis, they retained 34 documents from 2020, 25 from 2021, and 28 from 2022. The review discusses NC sources (plants, bacteria, algae, tunicates), isolation methods (acid hydrolysis, mechanical treatments, fermentation), and characterization techniques (TEM, XRD, mechanical testing).
**Key Results:** - **Morphology and Crystallinity:** CNCs are rod-like (width 5–40 nm, length 100–800 nm) with >90% crystallinity; CNFs are long, flexible fibrils (width 20–100 nm, length up to several μm) with lower crystallinity; BNC forms ribbon-shaped fibrils (width 8–10 nm, bundles 50–150 nm) with >80% crystallinity. - **Mechanical Properties:** CNCs have tensile strength 7500–7700 MPa and Young's modulus 130–250 GPa, comparable to carbon fiber. BNC single-fiber elastic modulus is 78 GPa, slightly higher than glass fiber (70 GPa). Never-dried BNC pellicle has tensile strength of 2 MPa at 99% water content. - **Biological Properties:** NCs show no or low cytotoxicity at concentrations <50–100 µg/mL for CNCs and <250 µg/mL for CNFs. At >100 µg/mL, CNCs can induce up to 55% cytotoxicity. BNC shows no cytotoxicity, DNA damage, apoptosis, or necrosis at 100–1000 µg/mL. In vivo, CNCs cause greater inflammatory response than CNFs; carboxylation of CNFs reduces toxicity. - **Wound Dressings:** NC-based hydrogels loaded with antimicrobials (e.g., levofloxacin, silver nanoparticles, curcumin) or growth factors (EGF) promote healing. A sprayable CNC-tobramycin hydrogel showed shear-thinning and self-healing properties. BNC-mesoporous silica nanoparticle hydrogels with bromothymol blue enabled pH sensing (color change from yellow to blue at pH 5.5–8). A CNF-based dual light-responsive hydrogel (CNFs-DLRIHWD) achieved >99.9% antibacterial activity against E. coli and S. aureus. - **Tissue Engineering:** 3D-printed NC hydrogels (e.g., alginate-CNFs) support cartilage, bone, and vascular tissue regeneration. BNC-alginate scaffolds with human umbilical vein endothelial cells (HUVEC) formed vascular-like structures. Silk fibroin-TEMPO-oxidized BNC inks induced lung epithelial stem cell orientation and proliferation after 7 days. - **Drug Delivery:** NC hydrogels enable controlled release responsive to pH, temperature, and NIR light. For example, mesoporous polydopamine-graphene oxide-CNF hydrogels released tetracycline hydrochloride (up to 35 wt% loading) faster under NIR or acidic pH. Succinylated CNC-poly(N-isopropylacrylamide) hydrogels showed pH- and temperature-responsive famotidine release.
**Clinical Implications:** NC-based hydrogels offer versatile platforms for advanced wound management, tissue regeneration, and targeted drug delivery. Their biocompatibility, tunable properties, and ability to incorporate stimuli-responsive features make them promising for personalized medicine. However, challenges remain in scaling production, standardizing characterization, and conducting long-term in vivo studies to ensure safety and efficacy. Future research should focus on environmentally friendly processing, improving mechanical properties for load-bearing tissues, and translating laboratory findings to commercial products.