The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, a gelatin methacryloyl (GelMA) patch is developed with an 11 × 11 array of MNs for minimally invasive sampling of ISF. The properties of the patch can be tuned by altering the concentration of the GelMA prepolymer and the crosslinking time; patches are created with swelling ratios between 293% and 423% and compressive moduli between 3.34 MPa and 7.23 MPa. The optimized GelMA MN patch demonstrates efficient extraction of ISF. Furthermore, it efficiently and quantitatively detects glucose and vancomycin in ISF in an in vivo study. This minimally invasive approach of extracting ISF with a GelMA MN patch has the potential to complement blood sampling for the monitoring of target molecules from patients.
Disorder of these physiological processes causes persistent inflammation and dys functional epithelial formation. Even tually, it leads to wound nonunion and increases the risk of infection. [2] Accu mulating evidence indicates that for accelerating diabetic wound healing, it is crucial to avoid excessive inflammation, including secretion of inflammatory fac tors in chronic wounds and inappropriate macrophage differentiation. [3] The clas sically activated macrophages (M1) and alternatively activated macrophages (M2) are two typical phenotypes of macro phages. [4] The M1 phenotype macro phages in diabetic wounds continue to release proinflammatory cytokines, such as tumor necrosis factor alpha (TNFα), which stimulate apoptosis of cells (fibro blasts, keratinocytes, and endothelial cells) and disorder collagen deposition, while M2 macrophages can accelerate fibroblast proliferation, orchestrate anti inflammatory responses, stabilize angiogenesis, and promote extracellular matrices (ECM) remodeling. [5] The ineffective transition of macrophages from M1 to M2 phenotype can lead to wound nonunion or scar formation. [6] Therefore, inducing the antiinflammatory transformation of macrophages could be a promising approach for developing clinical treatment of diabetic wounds. Diabeticwound treatment faces significant challenges in clinical settings. Alternative treatment approaches are needed. Continuous bleeding, disordered inflammatory regulation, obstruction of cell proliferation, and disturbance of tissue remodeling are the main characteristics of diabetic wound healing. Hydrogels made of either naturally derived or synthetic materials can potentially be designed with a variety of functions for managing the healing process of chronic wounds. Here, a hemostatic and anti-inflammatory hydrogel patch is designed for promoting diabetic wound healing. The hydrogel patch is derived from dual-cross-linked methacryloyl-substituted Bletilla Striata polysaccharide (B) and gelatin (G) via ultraviolet (UV) light. It is demonstrated that the B-G hydrogel can effectively regulate the M1/ M2 phenotype of macrophages, significantly promote the proliferation and migration of fibroblasts in vitro, and accelerate angiogenesis. It can boost wound closure by normalizing epidermal tissue regeneration and depositing collagen appropriately in vivo without exogenous cytokine supplementation. Overall, the B-G bioactive hydrogel can promote diabetic wound healing in a simple, economical, effective, and safe manner.
Transdermal delivery of water‐insoluble drugs via hydrogel‐based microneedle (MN) arrays is crucial for improving their therapeutic efficacies. However, direct loading of water‐insoluble drug into hydrophilic matrices remains challenging. Here, a biodegradable MN array patch that is fabricated from naturally derived polymer conjugates of gelatin methacryloyl and β‐cyclodextrin (GelMA‐β‐CD) is reported. When curcumin, an unstable and water‐insoluble anticancer drug, is loaded as a model drug, its stability and solubility are improved due to the formation of an inclusion complex. The polymer‐drug complex GelMA‐β‐CD/CUR can be formulated into MN arrays with sufficient mechanical strength for skin penetration and tunable drug release profile. Anticancer efficacy of released curcumin is observed in three‐dimensional B16F10 melanoma models. The GelMA‐β‐CD/CUR MN exhibits relatively higher therapeutic efficacy through more localized and deeper penetrated manner compared with a control nontransdermal patch. In vivo studies also verify biocompatibility and degradability of the GelMA‐β‐CD MN arrays patch.
Growth factors (GFs) play a crucial role in directing stem cell behavior and transmitting information between different cell populations for tissue regeneration. However, their utility as therapeutics is limited by their short half‐life within the physiological microenvironment and significant side effects caused by off‐target effects or improper dosage. “Smart” materials that can not only sustain therapeutic delivery over a treatment period but also facilitate on‐demand release upon activation are attracting significant interest in the field of GF delivery for tissue engineering. Three properties are essential in engineering these “smart” materials: 1) the cargo vehicle protects the encapsulated therapeutic; 2) release is targeted to the site of injury; 3) cargo release can be modulated by disease‐specific stimuli. The aim of this review is to summarize the current research on stimuli‐responsive materials as intelligent vehicles for controlled GF delivery; Five main subfields of tissue engineering are discussed: skin, bone and cartilage, muscle, blood vessel, and nerve. Challenges in achieving such “smart” materials and perspectives on future applications of stimuli‐responsive GF delivery for tissue regeneration are also discussed.
Despite the vital role of vaccines in fighting viral pathogens, effective vaccines are still unavailable for many infectious diseases. The importance of vaccines cannot be overstated during the outbreak of a pandemic, such as the coronavirus disease 2019 (COVID-19) pandemic. The understanding of genomics, structural biology, and innate/adaptive immunity have expanded the toolkits available for current vaccine development. However, sudden outbreaks and the requirement of population-level immunization still pose great challenges in today’s vaccine designs. Well-established vaccine development protocols from previous experiences are in place to guide the pipelines of vaccine development for emerging viral diseases. Nevertheless, vaccine development may follow different paradigms during a pandemic. For example, multiple vaccine candidates must be pushed into clinical trials simultaneously, and manufacturing capability must be scaled up in early stages. Factors from essential features of safety, efficacy, manufacturing, and distributions to administration approaches are taken into consideration based on advances in materials science and engineering technologies. In this review, we present recent advances in vaccine development by focusing on vaccine discovery, formulation, and delivery devices enabled by alternative administration approaches. We hope to shed light on developing better solutions for faster and better vaccine development strategies through the use of biomaterials, biomolecular engineering, nanotechnology, and microfabrication techniques.
The development of 3D printing has significantly advanced the field of bone tissue engineering by enabling the fabrication of scaffolds that faithfully recapitulate desired mechanical properties and architectures. In addition, computer-based manufacturing relying on patient-derived medical images permits the fabrication of customized modules in a patient-specific manner. In addition to conventional 3D fabrication, progress in materials engineering has led to the development of 4D printing, allowing time-sensitive interventions such as programed therapeutics delivery and modulable mechanical features. Therapeutic interventions established via multi-dimensional engineering are expected to enhance the development of personalized treatment in various fields, including bone tissue regeneration. Here, recent studies utilizing 3D printed systems for bone tissue regeneration are summarized and advances in 4D printed systems are highlighted. Challenges and perspectives for the future development of multi-dimensional printed systems toward personalized bone regeneration are also discussed.
A gelatin methacryloyl based microneedle patch has been developed for transdermal gene delivery both in vitro and in vivo.
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