The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy.

Exosomes, as therapeutically relevant cell-secreted extracellular vesicles, have attracted enormous interest because they participate in intercellular communication and facilitate wound healing. Stem cell-derived exosomes exhibit similar biological effects to source cells with the exception of low immunogenicity and no tumorigenicity, as well as superior efficacy in promoting wound healing. Exosomes accelerate wound healing by promoting angiogenesis and cell proliferation, as well as balancing inflammatory responses. Particularly, when exosomes are genetically modified or used in combination with materials, they can exhibit better comprehensive therapeutic properties, such as enriching active ingredients, targeted delivery, and physiological barrier to penetration, which are not available in traditional single products. Besides, exosomes have also been considered for diagnostic and therapeutic uses related to wounds, such as repairing complex wounds, enhancing graft success, treating related complications, and serving as diagnostic biomarkers. However, their clinical applications still face challenges, as reliable commercial products are not yet available. This review will focus on recent research advances that describe the characteristics and isolation of exosomes, introduce the sources of exosomes suitable for wound repair and related complications, illustrate the value of engineered exosomes and their development directions in the future, and provide evidence for the potential therapeutic application of exosomes in wound healing, as well as discuss potential risks, challenges, and solutions for future applications.

The purpose of this systematic review and meta-analysis is to assess the clinical effectiveness and safety of the medical hydrogel dressings used in skin wounds and therefore to weight the evidence for their clinical application. PubMed/Medline (1980-2019), Cochrane Library (1980-2019), ClinicalTrials.gov, Cochrane CENTRAL, Chinese Journal Full-text Database (CNKI, 1994-2019), and China Biomedy Medicine disc (CBM, 1978- 2019), Chinese Scientific Journal Database (VIP, 1989-2019) and Wanfang Database (WFDATA, 1980-2019) were searched to identify relevant clinical trials and studies. Forty-three studies that assessed hydrogel vs. non-hydrogel dressings were identified. Compared to the latter, hydrogel dressings associated with a significantly shortened healing time of degree II burn (superficial and deep) wounds, diabetic foot ulcers, traumatic skin injuries, radioactive skin injuries, dog bites, and body surface ulcers. In addition, hydrogel dressing obviously increased the cure rate of diabetic foot ulcers, surgical wounds, dog bites, and body surface ulcers. Moreover, hydrogel dressing significantly relieved pain in degree II burn (superficial and deep) wounds, traumatic skin injuries, and laser treatment-induced wounds. However, no significant differences obtained between hydrogel and non-hydrogel dressings in the healing time of surgical wounds, the cure rate of inpatients’ pressure ulcers, and phlebitis ulcers. This comprehensive systematic review and meta-analysis of the available evidence reveals that the application of hydrogel dressings advances the healing of various wound types and effectively alleviates the pain with no severe adverse reactions. These results strongly indicate that hydrogel products are effective and safe in wound management.

Over the past few years, different in vitro and in vivo studies have been highlighting the great potentiality of hyaluronic acid (HA) as a biomaterial in wound healing treatment thanks to its good capability to induce mesenchymal and epithelial cell growth and differentiation, angiogenesis, and collagen deposition. However, the need to improve its mechanical properties as well as its residence time has led scientists to study new functionalization strategies. In this work, chemically modified HA-based hydrogels were obtained by methacrylic and maleic functionalization. Methacrylated (MEHA) and maleated HA (MAHA) hydrogels have shown important physico-chemical properties. The present study provides a deeper insight into the biocompatibility of both synthesized materials and their effects on tissue inflammation using in vitro and in vivo models. To this aim, different cell lines involved in wound healing, human dermal fibroblasts, human adipose-derived stem cells and human umbilical vein endothelial cells, were seeded on MEHA and MAHA hydrogels. Furthermore, an inflammation study was carried out on a murine macrophage cell line to assess the effects of both hydrogels on inflammatory and anti-inflammatory interleukin production. The results showed that both MAHA and MEHA supported cell proliferation with anti-inflammation ability as highlighted by the increased levels of IL-10 (57.92 ± 9.87 pg mL⁻¹ and 68.08 ± 13.94 pg mL⁻¹, for MEHA and MAHA, respectively). To investigate the inflammatory response at tissue/implant interfaces, an in vivo study was also performed by subcutaneous implantation of the materials in BALB/c mice for up to 28 days. In these analyses, no significant chronic inflammation reaction was demonstrated in either MEHA or MAHA in the long-term implantation.

The migration and reepithelization of epidermal stem cells (ESCs) are the most critical processes in wound healing. The gaseous messenger nitric oxide (NO) has multiple biological effects, but its actions on ESCs are poorly understood. In this study, an NO donor, S-nitroso-N-acetylpenicillamine (SNAP), was found to facilitate the in vitro migration of human ESCs (huESCs) in both live-imaging and scratch models. In addition, pull-down assays demonstrated that SNAP could activate the small GTPases RhoA and Rac1 of the Rho family, but not Cdc42. Moreover, the effects of SNAP on the migration and F-actin polymerization of ESCs could be blocked by inhibitors of cGMP, PKG, RhoA or Rac1, and by a specific siRNA of RhoA or Rac1, but not by a Cdc42 inhibitor or siRNA. Furthermore, the roles of NO in ESC migration via cGMP-Rho GTPase signalling in vivo were confirmed by tracing 5-bromo-2-deoxyuridine (BrdU)-labelled cells in a superficial, partial-thickness scald mouse model. Thus, the present study demonstrated that the NO donor SNAP could promote huESC migration in vitro. Furthermore, NO was found to induce ESC migration via cGMP-Rho GTPase RhoA and Rac1 signalling, but not Cdc42 signalling, both in vivo and in vitro.