Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels.
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ABSTRACT:
SUBMITTER: Shirzaei Sani E
PROVIDER: S-EPMC6426459 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The in situ formation of adhesive hydrogels can repair of corneal defects but most focused on repairing focal stromal defects with diameters ≤ 3.5 mm because of their weak adhesion to wet tissues and fast biodegradation rate. Herein, a photocurable bioadhesive hydrogel that mimics the extracellular matrix (ECM) composition is developed for repairing 6-mm-diameter corneal stromal defects in rabbits. This biomacromolecule-based matrix hydrogel can undergo rapid gelling after UV light irradiation, exhibiting a high light transmittance and favorable mechanics. More importantly, this hydrogel maintained the viability and adhesion of cornea-derived cells and promoted their migration in vitro in 2D and 3D culture environments. Furthermore, in a rabbit corneal stromal defect model, the bioadhesive hydrogel could rapidly sealed wet corneal defects, resulting in epithelial wound coverage within 3-4 weeks, thereby contributing to a decrease in scar formation and increase in corneal stromal-neural regeneration during the 6-month follow-up. Thus, this work indicates that the biomacromolecule-based matrix hydrogel displays great potential for the regeneration of large-diameter corneal defects.
2022-09-28 | PXD037052 |
Project description:Corneal transplantation is an effective clinical treatment for corneal diseases, which, however, is limited by donor corneas. It is of great clinical value to develop bioadhesive corneal patches with functions of "Transparency" and "Epithelium & Stroma generation", as well as "Suturelessness" and "Toughness". To simultaneously meet the "T.E.S.T." requirements, a light-curable hydrogel is designed based on methacryloylated gelatin (GelMA), Pluronic F127 diacrylate (F127DA) & Aldehyded Pluronic F127 (AF127) co-assembled bi-functional micelles and collagen type I (COL I), combined with clinically applied corneal cross-linking (CXL) technology for repairing damaged cornea. The patch formed after 5 min of ultraviolet irradiation possesses transparent, highly tough, and strongly bio-adhesive performance. Multiple cross-linking makes the patch withstand deformation near 600% and exhibit a burst pressure larger than 400 mmHg, significantly higher than normal intraocular pressure (10-21 mmHg). Besides, the slower degradation than GelMA-F127DA&AF127 hydrogel without COL I makes hydrogel patch stable on stromal beds in vivo, supporting the regrowth of corneal epithelium and stroma. The hydrogel patch can replace deep corneal stromal defects and well bio-integrate into the corneal tissue in rabbit models within 4 weeks, showing great potential in surgeries for keratoconus and other corneal diseases by combining with CXL.
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Project description:Engineering mechanically robust bioadhesive hydrogels that can withstand large strains may open new opportunities for the sutureless sealing of highly stretchable tissues. While typical chemical modifications of hydrogels, such as increasing the functional group density of crosslinkable moieties and blending them with other polymers or nanomaterials have resulted in improved mechanical stiffness, the modified hydrogels have often exhibited increased brittleness resulting in deteriorated sealing capabilities under large strains. Furthermore, highly elastic hydrogels, such as tropoelastin derivatives are highly expensive. Here, gelatin methacryloyl (GelMA) is hybridized with methacrylate-modified alginate (AlgMA) to enable ion-induced reversible crosslinking that can dissipate energy under strain. The hybrid hydrogels provide a photocrosslinkable, injectable, and bioadhesive platform with an excellent toughness that can be tailored using divalent cations, such as calcium. This class of hybrid biopolymers with more than 600% improved toughness compared to GelMA may set the stage for durable, mechanically resilient, and cost-effective tissue sealants. This strategy to increase the toughness of hydrogels may be extended to other crosslinkable polymers with similarly reactive moieties.
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Project description:Corneal transplantation is the most effective clinical treatment for corneal defects, but it requires precise size of donor corneas, surgical sutures, and overcoming other technical challenges. Postoperative patients may suffer graft rejection and complications caused by sutures. Ophthalmic glues that can long-term integrate with the corneal tissue and effectively repair the focal corneal damage are highly desirable. Herein, a hybrid hydrogel consisting of porcine decellularized corneal stroma matrix (pDCSM) and methacrylated hyaluronic acid (HAMA) was developed through a non-competitive dual-crosslinking process. It can be directly filled into corneal defects with various shapes. More importantly, through formation of interpenetrating network and stable amide bonds between the hydrogel and adjacent tissue, the hydrogel manifested excellent adhesion properties to achieve suture-free repair. Meanwhile, the hybrid hydrogel not only preserved bioactive components from pDCSM, but also exhibited cornea-matching transparency, low swelling ratio, slow degradation, and enhanced mechanical properties, which was capable of withstanding superhigh intraocular pressure. The combinatorial hydrogel greatly improved the poor cell adhesion performance of HAMA, supported the viability, proliferation of corneal cells, and preservation of keratocyte phenotype. In a rabbit corneal stromal defect model, the experimental eyes treated with the hybrid hydrogel remained transparent and adhered intimately to the stroma bed with long-term retention, accelerated corneal re-epithelialization and wound healing. Giving the advantages of high bioactivity, low-cost, and good practicality, the dual-crosslinked hybrid hydrogel served effectively for long-term suture-free treatment and tissue regeneration after corneal defect.
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Project description:Corneal transplantation is the current gold standard treatment to restore visual acuity to patients with severe corneal diseases and injuries. Due to severe donor tissue shortage, efforts to develop a corneal equivalent have been made but the challenge remains unmet. Another issue of concern in ocular surgery is the difficult instillation and fast drainage of antibiotic ocular eye drops as bacterial infections can jeopardize implant success by delaying or impairing tissue healing. In this study, we developed antimicrobial silk-based hydrogels that have the potential to be photoactivated in situ, fully adapting to the corneal injury shape. Gentamicin-loaded methacrylated-silk (SilkMA) hydrogels were prepared within minutes using low UV intensity (3 mW/cm2 ). SilkMA gels provided a Young's modulus between 21 and 79 kPa together with a light transmittance spectrum and water content (83%-90%) similar to the human cornea. Polymer concentration (15%-25%) was found to offer a tool for tailoring the physical properties of the hydrogels. We confirmed that the methacrylation did not affect the material's in vitro degradation and biocompatibility by observing fibroblast adhesion and proliferation. Importantly, agar diffusion tests showed that the synthesized hydrogels were able to inhibit Staphylococcus aureus and Pseudomonas aeruginosa growth for 72 h. These characteristics along with their injectability and viscoelasticity demonstrate the potential of SilkMA hydrogels to be applied in several soft tissue engineering fields. As such, for the first time we demonstrate the potential of photocurable antimicrobial SilkMA hydrogels as a novel biomaterial to facilitate corneal regeneration.
| S-EPMC9313849 | biostudies-literature
Project description:Acellular cornea derived hydrogels provide significant advantages in preserving native corneal stromal keratocyte cells and endothelial cells. However, for clinical application, hydrogel physical properties need to be improved, and their role in corneal epithelial wound healing requires further investigation. In this study, an acellular porcine corneal stroma (APCS) hydrogel (APCS-gel) was successfully prepared from 20 mg/ml APCS, demonstrated optimal light transmittance and gelation kinetic properties and retained critical corneal ECM of collagens and growth factors. Compared with fibrin gel, the APCS-gel had a higher porosity ratio and faster nutrition diffusion with an accompanying improvement in the proliferation of primary rabbit corneal epithelial cells (RCECs) and stromal cells (RCSCs). These corneal cell types also displayed improved viability and cellular infiltration. Furthermore, the APCS-gel provides significant advantages in the preservation of RCECs stemness and enhancement of corneal wound healing in vitro and in vivo. After 7 days of culture, 3-4 layers of RCECs were formed on the APCS-gel in vitro, while only 1-2 layers were found on the fibrin gel. More corneal stem/progenitor cell phenotypes (K12-, p63+, ABCG2+) and proliferation phenotypes (Ki67+) were detected on the APCS-gel than fibrin gel. Using a corneal epithelial wound healing model, we also found faster reepithelization in corneas that received APCS-gel compared to fibrin gel. Additionally, our APCS-gel demonstrated better physical and biological properties when compared to Tisseel, a clinically used type of fibrin gel. In conclusion, our APCS-gel provided better corneal epithelial and stromal cell biocompatibility to fibrin gels and due to its transparency and faster gelation time could potentially be superior for clinical purposes. STATEMENT OF SIGNIFICANCE: Extracellular matrix (ECM) can be used to provide tissue specific physical microstructure and biochemical cues for tissue regeneration. Here, we produced an ECM hydrogel derived from acellular porcine cornea stroma (APCS-gel) that retained critical biological characteristics of the native tissue and provided significant transparency and fast gelation time. Our data demonstrated that the APCS-gel was superior to clinically used fibrin gel, as the APCS-gel showed high porosity and permeability, better corneal stromal keratocytes infiltration, increased cellular proliferation and retention of corneal epithelial cells stemness. The APCS-gel improved corneal wound healing in vitro and in vivo. This APCS-gel may have clinical utility for corneal diseases, and the more general approach used to make this hydrogel might be used in other tissues.
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Project description:ObjectiveHydrogel scaffolds hold promise for a myriad of tissue engineering applications, but often lack tissue-mimetic architecture. Therefore, in this work, we sought to develop a new technology for the incorporation of aligned tubular architecture within hydrogel scaffolds engineered from the bottom-up.ApproachWe report a platform fabrication technology-magnetic templating-distinct from other approaches in that it uses dissolvable magnetic alginate microparticles (MAMs) to form aligned columnar structures under an applied magnetic field. Removal of the MAMs yields scaffolds with aligned tubular microarchitecture that can promote cell remodeling for a variety of applications. This approach affords control of microstructure diameter and biological modification for advanced applications. Here, we sought to replicate the microarchitecture of the native nerve basal lamina using magnetic templating of hydrogels composed of glycidyl methacrylate hyaluronic acid and collagen I.Main resultsMagnetically templated hydrogels were characterized for particle alignment and micro-porosity. Overall MAM removal efficacy was verified by 96.8% removal of iron oxide nanoparticles. Compressive mechanical properties were well-matched to peripheral nerve tissue at 0.93 kPa and 1.29 kPa, respectively. In vitro, templated hydrogels exhibited approximately 36% faster degradation over 12 h, and were found to guide axon extension from dorsal root ganglia. Finally, in a pilot in vivo study utilizing a 10 mm rat sciatic nerve defect model, magnetically templated hydrogels demonstrated promising results with qualitatively increased remodeling and axon regeneration compared to non-templated controls.SignificanceThis simple and scalable technology has the flexibility to control tubular microstructure over long length scales, and thus the potential to meet the need for engineered scaffolds for tissue regeneration, including nerve guidance scaffolds.
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Project description:Surgical site infections cause significant postoperative morbidity and increased healthcare costs. Bioadhesives used to fill surgical voids and support wound healing are typically devoid of antibacterial activity. Here we report novel syringe-injectable bioadhesive hydrogels with inherent antibacterial properties prepared from mixing polydextran aldehyde and branched polyethylenimine. These adhesives kill both Gram-negative and Gram-positive bacteria, while sparing human erythrocytes. An optimal composition of 2.5?wt% oxidized dextran and 6.9?wt% polyethylenimine sets within seconds forming a mechanically rigid (~1,700?Pa) gel offering a maximum adhesive stress of ~2.8?kPa. A murine infection model showed that the adhesive is capable of killing Streptococcus pyogenes introduced subcutaneously at the bioadhesive's surface, with minimal inflammatory response. The adhesive was also effective in a cecal ligation and puncture model, preventing sepsis and significantly improving survival. These bioadhesives represent novel, inherently antibacterial materials for wound-filling applications.
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Project description:The management of corneal infections often requires complex therapeutic regimens involving the prolonged and high-frequency application of antibiotics that provide many challenges to patients and impact compliance with the therapeutic regimens. In the context of severe injuries that lead to tissue defects (e.g. corneal lacerations) topical drug regimens are inadequate and suturing is often indicated. There is thus an unmet need for interventions that can provide tissue closure while concurrently preventing or treating infection. In this study, we describe the development of an antibacterial bioadhesive hydrogel loaded with micelles containing ciprofloxacin (CPX) for the management of corneal injuries at risk of infection. The in vitro release profile showed that the hydrogel system can release CPX, a broad-spectrum antibacterial drug, for up to 24 h. Moreover, the developed CPX-loaded hydrogels exhibited excellent antibacterial properties against Staphylococcus aureus and Pseudomonas aeruginosa, two bacterial strains responsible for the most ocular infections. Physical characterization, as well as adhesion and cytocompatibility tests, were performed to assess the effect of CPX loading in the developed hydrogel. Results showed that CPX loading did not affect stiffness, adhesive properties, or cytocompatibility of hydrogels. The efficiency of the antibacterial hydrogel was assessed using an ex vivo model of infectious pig corneal injury. Corneal tissues treated with the antibacterial hydrogel showed a significant decrease in bacterial colony-forming units (CFU) and a higher corneal epithelial viability after 24 h as compared to non-treated corneas and corneas treated with hydrogel without CPX. These results suggest that the developed adhesive hydrogel system presents a promising suture-free solution to seal corneal wounds while preventing infection.
| S-EPMC7594650 | biostudies-literature
Project description:An original wireless stimulator for peripheral nerves based on a metal loop (diameter ≈1 mm) that is powered by a transcranial magnetic stimulator (TMS) and does not require circuitry components is reported. The loop can be integrated in a chitosan scaffold that functions as a graft when applied onto transected nerves (graft-antenna). The graft-antenna is bonded to rat sciatic nerves by a laser without sutures; it does not migrate after implantation and is able to trigger steady compound muscle action potentials for 12 weeks (CMAP ≈1.3 mV). Eight weeks postoperatively, axon regeneration is facilitated in transected nerves that are repaired with the graft-antenna and stimulated by the TMS for 1 h per week. The graft-antenna is an innovative and minimally-invasive device that functions concurrently as a wireless stimulator and adhesive scaffold for nerve repair.
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