All-in-one: harnessing multifunctional injectable natural hydrogels for ordered therapy of bacteria-infected diabetic wounds

Abstract Inflammation is a fundamental defensive response to harmful stimuli, but the overactivation of inflammatory responses is associated with most human diseases. Reactive oxygen species (ROS) are a class of chemicals that are generated after the incomplete reduction of molecular oxygen. At moderate levels, ROS function as critical signaling molecules in the modulation of various physiological functions, including inflammatory responses. However, at excessive levels, ROS exert toxic effects and directly oxidize biological macromolecules, such as proteins, nucleic acids and lipids, further exacerbating the development of inflammatory responses and causing various inflammatory diseases. Therefore, designing and manufacturing biomaterials that scavenge ROS has emerged an important approach for restoring ROS homeostasis, limiting inflammatory responses and protecting the host against damage. This review systematically outlines the dynamic balance of ROS production and clearance under physiological conditions. We focus on the mechanisms by which ROS regulate cell signaling proteins and how these cell signaling proteins further affect inflammation. Furthermore, we discuss the use of potential and currently available-biomaterials that scavenge ROS, including agents that were engineered to reduce ROS levels by blocking ROS generation, directly chemically reacting with ROS, or catalytically accelerating ROS clearance, in the treatment of inflammatory diseases. Finally, we evaluate the challenges and prospects for the controlled production and material design of ROS scavenging biomaterials. 

Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy

https://doi.org/10.1016/j.bioactmat.2022.01.004

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing

The development of natural hydrogels with sufficient strength and self-healing capacity to accelerate skin wound healing is still challenging. Herein, a hyaluronic acid nanocomposite hydrogel was developed based on aldehyde-modified sodium hyaluronate (AHA), hydrazide-modified sodium hyaluronate (ADA), and aldehyde-modified cellulose nanocrystals (oxi-CNC). This hydrogel was formed in situ using dynamic acylhydrazone bonds via a double-barreled syringe. This hydrogel exhibited improved strength and excellent self-healing ability. Furthermore, platelet-rich plasma (PRP) can be loaded in the hyaluronic acid nanocomposite hydrogels (ADAC) via imine bonds formed between amino groups on PRP (e.g., fibrinogen) and aldehyde groups on AHA or oxi-CNC to promote skin wound healing synergistically. As expected, ADAC hydrogel could protect and release PRP sustainably. In animal experiments, ADAC@PRP hydrogel significantly promoted full-thickness skin wound healing through enhancing the formation of granulation tissue, facilitating collagen deposition, and accelerating re-epithelialization and neovascularization. This self-healing nanocomposite hydrogel with PRP loading appears to be a promising candidate for wound therapy.

Self-Healing Hyaluronic Acid Nanocomposite Hydrogels with Platelet-Rich Plasma Impregnated for Skin Regeneration.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/agt2.39

Organic dye assemblies with aggregation-induced photophysical changes and their bio-applications

An intrinsically bioactive hydrogel with on-demand drug release behaviors for diabetic wound healing.

Cardiovascular diseases (CVDs) remain one of the major causes of mortality worldwide In response to this and other worldwide health epidemics, nanomedicine has emerged as a rapidly evolving discipline that involves the development of innovative nanomaterials and nanotechnologies and their applications in therapy and diagnosis Nanomedicine presents unique advantages over conventional medicines due to the superior properties intrinsic to nanoscopic therapies Once used mainly for cancer therapies, recently, tremendous progress has been made in nanomedicine that has led to an overall improvement in the treatment and diagnosis of CVDs This review elucidates the pathophysiology and potential targets of atherosclerosis and associated ischemic diseases It may be fruitful to pursue future work in the nanomedicine-mediated treatment of CVDs based on these targets A comprehensive overview is then provided featuring the latest preclinical and clinical outcomes in cardiovascular imaging, biomarker detection, tissue engineering, and nanoscale delivery, with specific emphasis on nanoparticles, nanostructured scaffolds, and nanosensors Finally, the challenges and opportunities regarding the future development and clinical translation of nanomedicine in related fields are discussed Overall, this review aims to provide a deep and thorough understanding of the design, application, and future development of nanomedicine for atherosclerosis and related ischemic diseases

Nanomedicine Approaches for Advanced Diagnosis and Treatment of Atherosclerosis and Related Ischemic Diseases

Osteoarthritis (OA), a chronic and degenerative joint disease, remains a challenge in treatment due to the lack of disease-modifying therapies. As a promising therapeutic agent, adipose-derived stem cells (ADSCs) have an effective anti-inflammatory and chondroprotective paracrine effect that can be enhanced by genetic modification. Unfortunately, direct cell delivery without matrix support often results in poor viability of therapeutic cells. Herein, a hydrogel implant approach that enabled intra-articular delivery of gene-engineered ADSCs was developed for improved therapeutic outcomes in a surgically induced rat OA model. An injectable extracellular matrix (ECM)-mimicking hydrogel was prepared as the carrier for cell delivery, providing a favorable microenvironment for ADSC spreading and proliferation. The ECM-mimicking hydrogel could reduce cell death during and post injection. Additionally, ADSCs were genetically modified to overexpress transforming growth factor-β1 (TGF-β1), one of the paracrine factors that exert an anti-inflammatory and pro-anabolic effect. The gene-engineered ADSCs overexpressing TGF-β1 (T-ADSCs) had an enhanced paracrine effect on OA-like chondrocytes, which effectively decreased the expression of tumor necrosis factor-alpha and increased the expression of collagen II and aggrecan. In a surgically induced rat OA model, intra-articular injection of the T-ADSC-loaded hydrogel markedly reduced cartilage degeneration, joint inflammation, and the loss of the subchondral bone. Taken together, this study provides a potential biomaterial strategy for enhanced OA treatment by delivering the gene-engineered ADSCs within an ECM-mimicking hydrogel.

Injectable hydrogel mediated delivery of gene-engineered adipose-derived stem cells for enhanced osteoarthritis treatment.

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An intrinsically bioactive hydrogel with on-demand drug release behaviors for diabetic wound healing.

Nanomedicine Approaches for Advanced Diagnosis and Treatment of Atherosclerosis and Related Ischemic Diseases

Injectable hydrogel mediated delivery of gene-engineered adipose-derived stem cells for enhanced osteoarthritis treatment.