Biopolymeric corneal lenticules by digital light processing based bioprinting: a dynamic substitute for corneal transplant.

Digital light processing (DLP) technology has gained significant attention for its ability to construct intricate structures for various applications in tissue modeling and regeneration. In this study, we aimed to design corneal lenticules using DLP bioprinting technology, utilizing dual network bioinks to mimic the characteristics of the human cornea. The bioink was prepared using methacrylated hyaluronic acid and methacrylated gelatin, where ruthenium salt and sodium persulfate were included for mediating photo-crosslinking while tartrazine was used as a photoabsorber. The bioprinted lenticules were optically transparent (85.45% ± 0.14%), exhibited adhesive strength (58.67 ± 17.5 kPa), and compressive modulus (535.42 ± 29.05 kPa) sufficient for supporting corneal tissue integration and regeneration. Puncture resistance tests and drag force analysis further confirmed the excellent mechanical performance of the lenticules enabling their application as potential corneal implants. Additionally, the lenticules demonstrated outstanding support for re-epithelialization and stromal regeneration when assessed with human corneal stromal cells. We generated implant ready corneal lenticules while optimizing bioink and bioprinting parameters, providing valuable solution for individuals suffering from various corneal defects and waiting for corneal transplants.

Bioinspired synthesis of bioactive glass nanocomposites for hyaluronic acid delivery to bone and skin.

In this study, we present nanocomposites of bioactive glass (BG) and hyaluronic acid (HA) (nano-BGHA) for effective delivery of HA to skin and bone. The synthesis of the nanocomposites has been carried out through the bio-inspired method, which is a modification of the traditional Stober's synthesis as it avoids using ethanol, ammonia, synthetic surfactants, or high-temperature calcination. This environmentally friendly, bio-inspired route allowed the synthesis of mesoporous nanocomposites with an average hydrodynamic radius of ∼190 nm and an average net surface charge of ∼-21 mV. Most nanocomposites are amorphous and bioactive in nature with over 70 % cellular viability for skin and bone cell lines even at high concentrations, along with high cellular uptake (90-100 %). Furthermore, the nanocomposites could penetrate skin cells in a transwell set-up and artificial human skin membrane (StratM®), thus depicting an attractive strategy for the delivery of HA to the skin. The purpose of the study is to develop nanocomposites of HA and BG that can have potential applications in non-invasive treatments that require the delivery of high molecular weight HA such as in the case of osteoarthritis, sports injury treatments, eye drops, wound healing, and some anticancer treatments, if further investigated. The presence of BG further enhances the range to bone-related applications. Additionally, the nanocomposites can have potential cosmeceutical applications where HA is abundantly used, for instance in moisturizers, dermal fillers, shampoos, anti-wrinkle creams, etc.

Bioactivity reinforced surface patch bound collagen-pectin hydrogel.

In this report, we discuss the design of a novel collagen/pectin (CP) hybrid composite hydrogel (CPBG) containing in-situ mineralized bioactive glass (BG) particles to simulate an integrative 3D cell environment. Systematic analysis of the CP sol revealed collagen and pectin molecules interacted regardless of both possessing similar net negative charge through the mechanism of surface patch binding interaction. Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) confirmed this associative interaction which resulted in the formation of a hybrid crosslinked network with the BG nanoparticles acting as pseudo crosslink junctions. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Analysis (EDAX) and Transmission Electron Microscopy (TEM) results confirmed uniform mineralization of BG particles, and their synergetic interaction with the network. The in-vitro bioactivity tests on CPBG indicated the formation of bone-like hydroxyapatite (Ca10(PO4)6(OH)2) microcrystals on its surface after interaction with simulated body fluid. This hydrogel was loaded with a model antifungal drug amphotericin-B (AmB) and tested against Candida albicans. The AmB release kinetics from the hydrogel followed the Fickian mechanism and showed direct proportionality to gel swelling behavior. Rheological analysis revealed the viscoelastic compatibility of CPBG for the mechanical load bearing applications. Cell viability tests indicated appreciable compatibility of the hydrogel against U2OS and HaCaT cell lines. FDA/PI on the hydrogel portrayed preferential U2OS cell adhesion on hydrophobic hydroxyapatite layer compared to hydrophilic surfaces, thereby promising the regeneration of both soft and hard tissues.

Emerging and innovative approaches for wound healing and skin regeneration: Current status and advances.

Current advances in skin tissue engineering and wound healing augur well for the development of split or full thickness skin substitutes to recapitulating the native functional skin. These engineered skin substitutes have fared successfully in recent years with exploration of various emerging technologies. As a result, recent clinical practice has been highly evolved incorporating various engineered skin substitutes as an adjunct to accelerate healing and improvement of quality of life in long-term. This review seeks to bring the researchers through various emerging and innovative approaches being developed and utilized for accelerating wound healing and skin regeneration. In order to attempt this, we reviewed various design considerations for skin repair and impact of several smart technologies viz., in situ 3D printing, portable bioprinters, electrosprayers and in situ forming hydrogels that have significantly improved wound healing and skin therapeutics. Furthermore, numerous cellular therapies such as effect of immunomodulation, stromal vascular fraction treatments, micro RNA (miRNA) and small interfering RNA (siRNA) based skin therapeutics have been thoroughly discussed. Finally, an update of clinical trials along with critical analysis of properties and benefits of different emerging technologies in healing certain types of wounds, prime challenges and future prospects in skin tissue engineering are discussed.

Nucleic acid delivery to differentiated retinal pigment epithelial cells using cell-penetrating peptide as a carrier.

Nucleic acid delivery to the eye is a promising treatment strategy for many retinal disorders. In this manuscript, retinal gene delivery with non-coated and chondroitin sulphate (CS) coated amphipathic and cationic peptides was tested. The transfection and gene knockdown efficiencies were evaluated in different retinal pigment epithelial (RPE) cell models including both dividing and differentiated cells. In addition, the mobility of peptide-based gene delivery systems was examined in porcine vitreous by particle tracking analysis. The results indicate that amphipathic and cationic peptides are safe in vitro and are capable of high transgene expression and gene knockdown in dividing cells. We further demonstrate that incorporation of CS improves the efficiency of gene delivery of peptide-based systems. Most importantly, the transgene expression mediated by both non-coated and CS coated peptides was high in differentiated as well as in human primary RPE cells which are typically difficult to transfect. Coating of peptide-based gene delivery systems with CS improved diffusion in the vitreous and enhanced the stability of the polyplexes. The results indicate that a peptide-based system can be fine-tuned as a promising approach for retinal gene delivery.

Dendrimeric amide- and carbamate-linked lysine-based efficient molecular transporters.

Amide- and carbamate-linked dendrimeric oligomers are reported as molecular transporters. They effectively complex with pDNA and transport it into cells at an efficiency superior to Lipofectamine, when complexation is carried out by incubation overnight. The carbamate-linked K2C is superior to amide-linked K2A; their pDNA complexes have very low associated cytotoxicity.