Emerging trends in polysaccharide-based smart PEGylated hydrogels for biomedical applications.

Wound healing progresses through many key cellular activities, including fibroblast and keratinocyte proliferation and angiogenesis. This study explored the wound-healing potential of reactive oxygen species (ROS)-generating hyaluronic acid (HA) hydrogels. We fabricated a chlorin e6-conjugated HA (Ce6-HA) hydrogel that generates ROS when subjected to irradiation from an LED light source. In vitro studies revealed that the ROS generated by the Ce6-HA hydrogels enhanced the proliferation of fibroblasts and keratinocytes. Further, the fibroblasts were found to have high levels of intracellular ROS, elevated expression of p-ERK1/2, p-p38 MAPK, p-Akt, and cyclin D1 proteins, and enhanced collagen deposition. Moreover, the Ce6-HA hydrogel also promoted endothelial angiogenesis in vitro. In vivo studies demonstrated the ROS-generating HA hydrogels significantly improved wound closure and tissue regeneration compared to control groups. The Ce6-HA hydrogel-treated group exhibited accelerated wound healing, with enhanced fibroblast proliferation, increased keratinocyte proliferation, and better angiogenesis. Histopathological and immunohistochemical analyses showed elevated levels of key growth factors and signaling molecules, which are critical to wound healing. The controlled ROS generation from the Ce6-HA hydrogels activated broader molecular pathways necessary for effective skin tissue repair. Therefore, ROS-triggering HA hydrogels could be a viable approach to accelerate recovery and reduce scarring in clinical settings.

Polysaccharide-based hydrogels have emerged as indispensable materials in tissue engineering and wound healing, offering a unique combination of biocompatibility, biodegradability, and structural versatility. Indeed, their three-dimensional polymeric network and high water content closely resemble the natural extracellular matrix, creating a microenvironment for cell growth, differentiation, and tissue regeneration. Moreover, their intrinsic biodegradability, tunable chemical structure, non-toxicity, and minimal immunogenicity make them optimal candidates for prolonged drug delivery systems. Notwithstanding numerous advantages, these polysaccharide-based hydrogels are confronted with setbacks such as variability in material qualities depending on their source, susceptibility to microbial contamination, unregulated water absorption, inadequate mechanical strength, and unpredictable degradation patterns which limit their efficacy in real-world applications. This review summarizes recent advancements in the application of polysaccharide-based hydrogels, including cellulose, starch, pectin, zein, dextran, pullulan and hyaluronic acid as innovative solutions in wound healing, drug delivery, tissue engineering, and regenerative medicine. Future research should concentrate on optimizing hydrogel formulations to enhance their effectiveness in regenerative medicine and antimicrobial therapy.

Immediate treatment for cutaneous injuries is a realistic approach to improve the healing rate and minimise the risk of complications. Multifunctional biomaterials have been proven to be a potential strategy for chronic skin wound management, especially for future advancements in precision medicine. Hence, antioxidant incorporated biomaterials play a vital role in the new era of tissue engineering. A bibliographic investigation was conducted on articles focusing on in vitro, in vivo, and clinical studies that evaluate the effect and the antioxidants mechanism exerted by epigallocatechin gallate (EGCG) in wound healing and its ability to act as reactive oxygen species (ROS) scavengers. Over the years, EGCG has been proven to be a potent antioxidant efficient for wound healing purposes. Therefore, several novel studies were included in this article to shed light on EGCG incorporated biomaterials over five years of research. However, the related papers under this review’s scope are limited in number. All the studies showed that biomaterials with scavenging ability have a great potential to combat chronic wounds and assist the wound healing process against oxidative damage. However, the promising concept has faced challenges extending beyond the trial phase, whereby the implementation of these biomaterials, when exposed to an oxidative stress environment, may disrupt cell proliferation and tissue regeneration after transplantation. Therefore, thorough research should be executed to ensure a successful therapy.

The bioengineering application of hyaluronic acid in tissue regeneration and repair

This review article examines functionalized nanofibers and their potential to revolutionize drug delivery systems and enhance their biomedical applications. By leveraging the high surface- area-to-volume ratio and tunable physicochemical properties of nanofibers, the limitations of conventional drug delivery methods can be addressed. These nanofibers can be engineered for the controlled and sustained release of drugs, growth factors, and bioactive agents to improve treatment efficacy and mitigate side effects. Furthermore, the versatility of functionalized nanofibers in various biomedical fields has been investigated. In tissue engineering, nanofibers serve as scaffolds that emulate the extracellular matrix and facilitate cell adhesion, proliferation, and differentiation, thus demonstrating the potential for regenerating tissues and organs, including bone, cartilage, and nerve repair. This review also explores their application in wound healing, where nanofiber dressings incorporating antimicrobial agents and growth factors can expedite healing, prevent infections, and minimize scarring, benefiting patients with chronic wounds, burns, and other complex skin injuries. Additionally, this article discusses the potential of functionalized nanofibers for developing innovative medical devices with therapeutic and diagnostic functions. The integration of sensing elements and drug-releasing components into nanofiber platforms has resulted in multifunctional devices capable of monitoring physiological parameters, detecting biomarkers, and delivering targeted therapies based on biological cues. The versatility of these nanofibers may enable the development of combination products that can incorporate multiple therapeutic modalities into a single platform, potentially enhancing the management of complex diseases and improving patient outcomes. The article aims to provide a comprehensive overview of the current state and future trajectory of electrospinning technology.

Wound healing is a complex process involving cell proliferation, migration, and extracellular matrix (ECM) remodeling. Extracellular vesicles (EVs) or exosomes derived from adipose tissue-derived stem cells (ASCs) are emerging as promising alternatives to cell therapy for advanced wound healing. Hyaluronic acid (HA), a major component of the skin ECM, is widely utilized in wound dressings and dermal fillers. This study aimed to investigate the effects of ASC-derived exosomes (ASC-EXOs) on human dermal fibroblasts (HDFs) and their potential combination with HA in in vivo wound healing and dermal filler models. In HDFs, ASC-EXOs increased cell proliferation and migration. ASC-EXOs also upregulated the expression of genes involved in cell proliferation and wound healing while stimulating collagen production in HDFs. In a porcine wound healing model, topical treatment with a combination of HA and ASC-EXOs led to higher wound closure rates compared to HA alone. Histological examination showed increased re-epithelialization and collagen type III deposition in wounds treated with the combination of HA and ASC-EXOs. In a mouse dermal filler model, tissues injected with the combination of HA and ASC-EXOs exhibited thicker tissue layers, increased vascularization, enhanced infiltration of myofibroblasts, and higher levels of collagen III and collagen fiber content compared to HA alone. These findings suggest that ASC-EXOs have beneficial effects on cell proliferation, migration, and gene expression related to wound healing, and they may accelerate wound closure and promote tissue regeneration. Furthermore, the combination of HA and ASC-EXOs may enhance wound healing and tissue remodeling, indicating its potential for both clinical and regenerative aesthetic applications in skin repair and regeneration.

Umbilical remnant allograft application in the treatment of erosive pustular dermatosis of the scalp

Age-Related Changes in Pericellular Hyaluronan Organization Leads to Impaired Dermal Fibroblast to Myofibroblast Differentiation

ABSTRACTWound healing is a multipart and dynamic process of replacing devitalized and damaged cellular structures and tissue layers. Numerous conventional wound dressings are employed for the management of wounds but there is a lack of absolute and versatile choice. An ideal wound healing modality should provide a moist environment, offer protection from secondary infections, eliminate wound exudate, and stimulate tissue regeneration. Hyaluronic acid (HA) has been known to promote angiogenesis, granulation tissue formation, remodeling of extracellular matrix (ECM), and wound healing. Accumulation and turnover of ECM is a hallmark of tissue injury, repair, and remodeling in wound healing. HA is a major component of ECM and plays an important role in regulating tissue injury, accelerating tissue repair, and controlling disease outcomes. A wide range of in vitro, in vivo, and clinical studies have demonstrated the wound healing efficacy of HA-based biomaterials not only in the treatment of wound in the tympanic membrane, skin, and articular cartilage but also in tracheal and corneal wound healing. Recent progress and improved therapeutic efficacy achieved through partial modification and formation of HA-based biomaterials, including HA-scaffolds, sponge-like hydrogels, anti-adhesive sheets, cultured dermal substitutes, thin membranes, and dermal matrix grafts have been discussed. The current review summarizes the evidence for the therapeutic effectiveness of HA-based biomaterials in the treatment of traumatic, surgical, and chronic wounds and tissue regeneration.

Hyaluronic acid (HA) has been found to play important roles in tissue regeneration and wound-healing processes. Fetal tissue with a high concentration of HA heals rapidly without scarring. The present study employed HA formed into three-dimensional strands with or without keratinocytes to treat full-thickness skin incision wounds in rats. Wound closure rates of HA strand grafts both with and without keratinocytes were substantially enhanced. The closure times of both HA grafts were less than 1 day (average 16 h), about 1/7 that of the contralateral control incisions (114 h, p <.01). Average wound areas after 10 days were HA-only graft: 0.151 mm2 +/- 0.035; HA + cell grafts: 0.143 mm2 +/- 0.036 and controls: 14.434 mm2 +/- 1.175, experimental areas were 1% of the controls (p < 0.01). Transforming growth factor (TGF) beta1 measured by immunostaining was remarkably reduced in HA-treated wounds compared to the controls. In conclusion, HA grafts appeared to produce a fetal-like environment with reduced TGF-beta1, which is known to be elevated in incipient scars. The HA strands with or without cultured cells may potentially improve clinical wound healing as well as reduce scar formation.

This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol-ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system's efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.

To overcome the dual challenges of excessive reactive oxygen species (ROS) and insufficient tissue adhesion in skin wound healing, this study developed a multifunctional hydrogel, designated Gam/Ct-HA@Czo, which integrates ROS-scavenging and tissue-adhesive capabilities. The hydrogel utilized methacrylated gelatin (Gam) as the polymeric matrix and incorporated chitin (Ct), hyaluronic acid (HA), and cerium–zirconium oxide (Czo) nanoparticles to establish a multifunctional hydrogel system. The developed hydrogel demonstrated an ROS scavenging efficiency of 46.8% and a tissue adhesion strength of 16.3 Kpa. It also possessed favorable antioxidant properties, self-healing capacity, and in vitro biocompatibility, which supported its role in effectively promoting tissue regeneration and repair. In a mouse full-thickness skin defect model, treatment with Gam/Ct-HA@Czo hydrogel significantly accelerated wound closure, promoted epithelial regeneration, and facilitated the orderly deposition of collagen. The findings demonstrate that the rational integration of multifunctional components into a hydrogel system offers a promising strategy for enhancing wound repair and regeneration.

Hydrogels play a crucial role due to their high-water content and 3D structure, which make them ideal for various applications in biomedicine, sensing, and beyond. They can be prepared from a variety of biomaterials, polymers, and their combinations, allowing for versatility in properties and applications. Hydrogels include natural types derived from collagen, gelatin, alginate, and hyaluronic acid, as well as synthetic types based on polyethylene glycol (PEG), polyvinyl alcohol (PVA), and polyacrylamide (PAAm). Each type possesses distinct properties, such as mechanical strength, biodegradability, and biocompatibility, which can be tailored for applications such as wound healing, contact lenses, 3D bioprinting, and tissue engineering. The high-water content of hydrogels mimics natural tissue environments, promoting cell growth and allowing nutrient and waste exchange, which supports the development of functional tissues. They serve as scaffolds in tissue engineering applications, including wound healing, cartilage and bone regeneration, vascular tissue engineering, and organ-on-a-chip systems. Additionally, hydrogels can encapsulate and deliver therapeutic agents, such as growth factors or drugs, to specific target sites in the body. Hydrogels can be prepared through three primary methods: physical crosslinking, which relies on non-covalent interactions such as physical entanglements or hydrogen bonding; chemical crosslinking, which forms covalent bonds between polymer chains to create a stable structure; and irradiation-based crosslinking, where UV irradiation induces rapid hydrogel formation. The choice of crosslinking method depends on the desired properties and applications of the hydrogel. By providing a biomimetic environment, hydrogels facilitate cell growth and differentiation, support tissue formation, and aid in the regeneration of damaged or diseased tissues while delivering therapeutic agents. This review focuses on the critical advancements in processing routes for hydrogel development, summarizing the characterization and application of hydrogels. It also details key applications, including wound healing and cartilage and bone regeneration, as well as the challenges and future perspectives in the field.

A synergistically antimicrobial and antioxidant hyaluronic acid hydrogel for infected wounds

Within ultraviolet radiation, ultraviolet B (UVB) is the most energetic and damaging to humans. At the protein level, UVB irradiation downregulates the expression of antioxidant enzymes leading to the accumulation of reactive oxygen species (ROS). Due to lacking of a global analysis of UVB-modulated corneal proteome, we investigate in vitro the mechanism of UVB-induced corneal damage to determine whether hyaluronic acid (HA) is able to reduce UVB irradiation-induced injury in human corneal epithelial cells. Accordingly, human corneal epithelial cell lines (HCE-2) were irradiated with UVB, followed by incubation with low molecular weight HA (LMW-HA, 100 kDa) or high molecular weight HA (HMW-HA, 1,000 kDa) to investigate the physiologic protection of HMW-HA in UVB-induced corneal injury, and to perform a global proteomic analysis. The data demonstrated that HA treatment protects corneal epithelial cells in the UVB-induced wound model, and that the molecular weight of HA is a crucial factor. Only HMW-HA significantly reduces the UVB-induced cytotoxic effects in corneal cells and increases cell migration and wound-healing ability. In addition, proteomic analysis showed that HMW-HA might modulate cytoskeleton regulation, signal transduction, biosynthesis, redox regulation, and protein folding to stimulate wound healing and to prevent these UVB-damaged cells from cell death. Further studies evidenced membrane-associated progesterone receptor component 1 (mPR) and malate dehydrogenase (MDH2) play essential roles in protecting corneal cells from UVB irradiation. This study reports on UVB-modulated cellular proteins that might play an important role in UVB-induced corneal cell injury and show HMW-HA to be a potential substance for protecting corneal cells from UVB-induced injury.