The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

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Diverse Applications of Nanomedicine

As a mussel-inspired material, polydopamine (PDA), possesses many properties, such as a simple preparation process, good biocompatibility, strong adhesive property, easy functionalization, outstanding photothermal conversion efficiency, and strong quenching effect. PDA has attracted increasingly considerable attention because it provides a simple and versatile approach to functionalize material surfaces for obtaining a variety of multifunctional nanomaterials. In this review, recent significant research developments of PDA including its synthesis and polymerization mechanism, physicochemical properties, different nano/microstructures, and diverse applications are summarized and discussed. For the sections of its applications in surface modification and biomedicine, we mainly highlight the achievements in the past few years (2016-2019). The remaining challenges and future perspectives of PDA-based nanoplatforms are discussed rationally at the end. This timely and overall review should be desirable for a wide range of scientists and facilitate further development of surface coating methods and the production of PDA-based materials.

Versatile Polydopamine Platforms: Synthesis and Promising Applications for Surface Modification and Advanced Nanomedicine

During the resorbable-polymer-boom of the 1970s and 1980s, polycaprolactone (PCL) was used in the biomaterials field and a number of drug-delivery devices. Its popularity was soon superseded by faster resorbable polymers which had fewer perceived disadvantages associated with long term degradation (up to 3-4 years) and intracellular resorption pathways; consequently, PCL was almost forgotten for most of two decades. Recently, a resurgence of interest has propelled PCL back into the biomaterials-arena. The superior rheological and viscoelastic properties over many of its aliphatic polyester counterparts renders PCL easy to manufacture and manipulate into a large range of implants and devices. Coupled with relatively inexpensive production routes and FDA approval, this provides a promising platform for the production of longer-term degradable implants which may be manipulated physically, chemically and biologically to possess tailorable degradation kinetics to suit a specific anatomical site. This review will discuss the application of PCL as a biomaterial over the last two decades focusing on the advantages which have propagated its return into the spotlight with a particular focus on medical devices, drug delivery and tissue engineering.

The return of a forgotten polymer : Polycaprolactone in the 21st century

Recent progress in drug delivery

Infection is a major obstacle to wound healing. To enhance the healing of infected wounds, dressings with antibacterial activities and multifunctional properties to promote wound healing are highly desirable. Herein, gelatin-grafted-dopamine (GT-DA) and polydopamine-coated carbon nanotubes (CNT-PDA) were used to engineer antibacterial, adhesive, antioxidant and conductive GT-DA/chitosan/CNT composite hydrogels through the oxidative coupling of catechol groups using a H2O2/HRP (horseradish peroxidase) catalytic system. The addition of the antibiotic doxycycline endowed the hydrogels with antimicrobial activity to treat infected full-thickness defect wounds. Additionally, CNT-PDA endowed these hydrogels with an excellent photothermal effect, leading to good in vitro and in vivo antibacterial activities against Gram-positive and Gram-negative bacteria. The catechol group and polydopamine imparted tissue adhesiveness, and the hemostatic and antioxidant abilities of these hydrogels were also investigated. The porosity, degradability, swelling, rheological, mechanical, and conductive behaviors of these hydrogels were finely regulated by changing the concentration of CNT-PDA. Hemolysis and cytocompatibility tests using L929 fibroblast cells confirmed the good biocompatibility of these hydrogels. The wound closure, collagen deposition, histomorphological examination and immunofluorescence staining results demonstrated the excellent effects of these hydrogels in an infected full-thickness mouse skin defect wound. In summary, the adhesive antibacterial and conductive GT-DA/chitosan/CNT hydrogels showed great potential as multifunctional bioactive dressings for the treatment of infected wounds.

Mussel-inspired, antibacterial, conductive, antioxidant, injectable composite hydrogel wound dressing to promote the regeneration of infected skin.

Skin interstitial fluid (ISF) is an emerging source of biomarkers for disease diagnosis and prognosis. Microneedle (MN) patch has been identified as an ideal platform to extract ISF from the skin due to its pain-free and easy-to-administrated properties. However, long sampling time is still a serious problem which impedes timely metabolic analysis. In this study, a swellable MN patch that can rapidly extract ISF is developed. The MN patch is made of methacrylated hyaluronic acid (MeHA) and further crosslinked through UV irradiation. Owing to the supreme water affinity of MeHA, this MN patch can extract sufficient ISF in a short time without the assistance of extra devices, which remarkably facilitates timely metabolic analysis. Due to covalent crosslinked network, the MN patch maintains the structure integrity in the swelling hydrated state without leaving residues in skin after usage. More importantly, the extracted ISF metabolites can be efficiently recovered from MN patch by centrifugation for the subsequent offline analysis of metabolites such as glucose and cholesterol. Given the recent trend of easy-to-use point-of-care devices for personal healthcare monitoring, this study opens a new avenue for the development of MN-based microdevices for sampling ISF and minimally invasive metabolic detection.

A Swellable Microneedle Patch to Rapidly Extract Skin Interstitial Fluid for Timely Metabolic Analysis.

Eye diseases and injuries impose a significant clinical problem worldwide. Safe and effective ocular drug delivery is, however, challenging due to the presence of ocular barriers. Here we report a strategy using an eye patch equipped with an array of detachable microneedles. These microneedles can penetrate the ocular surface tissue, and serve as implanted micro-reservoirs for controlled drug delivery. The biphasic drug release kinetics enabled by the double-layered micro-reservoirs largely enhances therapeutic efficacy. Using corneal neovascularization as the disease model, we show that delivery of an anti-angiogenic monoclonal antibody (DC101) by such eye patch produces ~90% reduction of neovascular area. Furthermore, quick release of an anti-inflammatory compound (diclofenac) followed by a sustained release of DC101 provides synergistic therapeutic outcome. The eye patch application is easy and minimally invasive to ensure good patient compliance. Such intraocular drug delivery strategy promises effective home-based treatment of many eye diseases.

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Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery.

Electropolymerization of dopamine for surface modification of complex-shaped cardiovascular stents.

Infections associated with medical devices have become a major concern. The adhesion of bacteria to the devices’ surfaces during the initial 24 h is believed to be a “decisive period” for implant-associated infections, which pose key challenges to optimal antiadhesion of microbes in this period. Herein, we have designed and constructed a (heparin/chitosan)10–(polyvinylpyrrolidone/poly(acrylic acid))10 [(HEP/CHI)10–(PVP/PAA)10] multilayer film by layer-by-layer self-assembly. Assembly of the underlying (HEP/CHI)10 multilayer film is based on electrostatic interactions, showing the properties of contact killing of bacteria. Deposition of the top (PVP/PAA)10 multilayer film is based on hydrogen bond interactions. The PAA molecules are then cross-linked to form anhydride groups by thermal treatment at 110 °C for 16 h. Therefore, it shows a top-down degradable capability in the determined period, leading to almost no adhesion of bacteria in 24 h. Our system combining the adhesion resistance and the contact kil...

Hao Chang

Papers

A Swellable Microneedle Patch to Rapidly Extract Skin Interstitial Fluid for Timely Metabolic Analysis.

Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery.

Electropolymerization of dopamine for surface modification of complex-shaped cardiovascular stents.

Construction of Degradable Multilayer Films for Enhanced Antibacterial Properties

Polydopamine Nanocoating for Effective Photothermal Killing of Bacteria and Fungus upon Near-Infrared Irradiation