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Emerging Bioprinting for Wound Healing. Advanced materials (Deerfield Beach, Fla.) Bioprinting has attracted much attention due to its suitability for fabricating biomedical devices. In particular, bioprinting has become one of the growing centers in the field of wound healing, with various types of bioprinted devices being developed, including 3D scaffolds, microneedle patches, and flexible electronics. Bioprinted devices can be designed with specific biostructures and biofunctions that closely match the shape of wound sites and accelerate the regeneration of skin through various approaches. Herein, a comprehensive review of the bioprinting of smart wound dressings is presented, emphasizing the crucial effect of bioprinting in determining biostructures and biofunctions. The review begins with an overview of bioprinting techniques and bioprinted devices, followed with an in-depth discussion of polymer-based inks, modification strategies, additive ingredients, properties, and applications. The strategies for the modification of bioprinted devices are divided into seven categories, including chemical synthesis of novel inks, physical blending, coaxial bioprinting, multimaterial bioprinting, physical absorption, chemical immobilization, and hybridization with living cells, and examples are presented. Thereafter, the frontiers of bioprinting and wound healing, including 4D bioprinting, artificial intelligence-assisted bioprinting, and in situ bioprinting, are discussed from a perspective of interdisciplinary sciences. Finally, the current challenges and future prospects in this field are highlighted. 10.1002/adma.202304738
Device-assisted transdermal drug delivery. Lee Hyunjae,Song Changyeong,Baik Seungmin,Kim Dokyoon,Hyeon Taeghwan,Kim Dae-Hyeong Advanced drug delivery reviews Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small-molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real-time analysis of physiological cues is highlighted. 10.1016/j.addr.2017.08.009
Engineering Microneedle Patches for Improved Penetration: Analysis, Skin Models and Factors Affecting Needle Insertion. Nano-micro letters Transdermal microneedle (MN) patches are a promising tool used to transport a wide variety of active compounds into the skin. To serve as a substitute for common hypodermic needles, MNs must pierce the human stratum corneum (~ 10 to 20 µm), without rupturing or bending during penetration. This ensures that the cargo is released at the predetermined place and time. Therefore, the ability of MN patches to sufficiently pierce the skin is a crucial requirement. In the current review, the pain signal and its management during application of MNs and typical hypodermic needles are presented and compared. This is followed by a discussion on mechanical analysis and skin models used for insertion tests before application to clinical practice. Factors that affect insertion (e.g., geometry, material composition and cross-linking of MNs), along with recent advancements in developed strategies (e.g., insertion responsive patches and 3D printed biomimetic MNs using two-photon lithography) to improve the skin penetration are highlighted to provide a backdrop for future research. 10.1007/s40820-021-00611-9
Polymeric long-acting drug delivery systems (LADDS) for treatment of chronic diseases: Inserts, patches, wafers, and implants. Abdelkader Hamdy,Fathalla Zeinab,Seyfoddin Ali,Farahani Mojtaba,Thrimawithana Thilini,Allahham Ayman,Alani Adam W G,Al-Kinani Ali A,Alany Raid G Advanced drug delivery reviews Non-oral long-acting drug delivery systems (LADDS) encompass a range of technologies for precisely delivering drug molecules into target tissues either through the systemic circulation or via localized injections for treating chronic diseases like diabetes, cancer, and brain disorders as well as for age-related eye diseases. LADDS have been shown to prolong drug release from 24 h up to 3 years depending on characteristics of the drug and delivery system. LADDS can offer potentially safer, more effective, and patient friendly treatment options compared to more invasive modes of drug administration such as repeated injections or minor surgical intervention. Whilst there is no single technology or definition that can comprehensively embrace LADDS; for the purposes of this review, these systems include solid implants, inserts, transdermal patches, wafers and in situ forming delivery systems. This review covers common chronic illnesses, where candidate drugs have been incorporated into LADDS, examples of marketed long-acting pharmaceuticals, as well as newly emerging technologies, used in the fabrication of LADDS. 10.1016/j.addr.2021.113957
Intradermal and transdermal drug delivery using microneedles - Fabrication, performance evaluation and application to lymphatic delivery. Sabri Akmal H,Kim Yujin,Marlow Maria,Scurr David J,Segal Joel,Banga Ajay K,Kagan Leonid,Lee Jong Bong Advanced drug delivery reviews The progress in microneedle research is evidenced by the transition from simple 'poke and patch' solid microneedles fabricated from silicon and stainless steel to the development of bioresponsive systems such as hydrogel-forming and dissolving microneedles. In this review, we provide an outline on various microneedle fabrication techniques which are currently employed. As a range of factors, including materials, geometry and design of the microneedles, affect the performance, it is important to understand the relationships between them and the resulting delivery of therapeutics. Accordingly, there is a need for appropriate methodologies and techniques for characterization and evaluation of microneedle performance, which will also be discussed. As the research expands, it has been observed that therapeutics delivered via microneedles has gained expedited access to the lymphatics, which makes them a favorable delivery method for targeting the lymphatic system. Such opportunity is valuable in the area of vaccination and treatment of lymphatic disorders, which is the final focus of the review. 10.1016/j.addr.2019.10.004
Long-acting transdermal drug delivery formulations: Current developments and innovative pharmaceutical approaches. Advanced drug delivery reviews Transdermal administration remains an active research and development area as an alternative route for long-acting drug delivery. It avoids major drawbacks of conventional oral (gastrointestinal side effects, low drug bioavailability, and need for multiple dosing) or parenteral routes (invasiveness, pain, and psychological stress and bio-hazardous waste generated from needles), thereby increasing patient appeal and compliance. This review focuses on the current state of long-acting transdermal drug delivery, including adhesive patches, microneedles, and molecularly imprinted polymeric systems. Each subsection describes an approach including key considerations in formulation development, design, and process parameters with schematics. An overview of commercially available conventional (adhesive) patches for long-acting drug delivery (longer than 24 h), the reservoir- and matrix-type systems under preclinical evaluation, as well as the advanced transdermal formulations, such as the core-shell, nanoformulations-incorporated and stimuli-responsive microneedles, and 3D-printed and molecularly imprinted polymers that are in development, is also provided. Finally, we elaborated on translational aspects, challenges in patch formulation development, and future directions for the clinical advancement of new long-acting transdermal products. 10.1016/j.addr.2024.115326
Insulin delivery systems combined with microneedle technology. Jin Xuan,Zhu Dan Dan,Chen Bo Zhi,Ashfaq Mohammad,Guo Xin Dong Advanced drug delivery reviews Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs ("poke and patch"), hollow MNs ("poke and flow") and reservoir-based swelling MNs ("poke and swell R-type"), and drug loaded MNs include coated MNs ("coat and poke"), dissolving MNs ("poke and release") and insulin incorporated swelling MNs ("poke and swell I-type"). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. "Poke and patch" approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. "Poke and flow" approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. "Poke and release" approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. "Poke and swell R-type" can be seen as a combination of "poke and flow" and "poke and patch" approach, while "poke and swell I-type" is an approach between "coat and poke" and "poke and release" approach. Insulin MNs are promising for painless diabetes therapeutics, and additional efforts for addressing fundamental issues including the drug loading, the PK/PD profile, the storage and the safety of insulin MNs will accelerate the clinical transformation. 10.1016/j.addr.2018.03.011
Exploiting Unique Features of Microneedles to Modulate Immunity. Advanced materials (Deerfield Beach, Fla.) Microneedle arrays (MNAs) are small patches containing hundreds of short projections that deliver signals directly to dermal layers without causing pain. These technologies are of special interest for immunotherapy and vaccine delivery because they directly target immune cells concentrated in the skin. The targeting abilities of MNAs result in efficient immune responses-often more protective or therapeutic-compared to conventional needle delivery. MNAs also offer logistical benefits, such as self-administration and transportation without refrigeration. Thus, numerous preclinical and clinical studies are exploring these technologies. Here the unique advantages of MNA, as well as critical challenges-such as manufacturing and sterility issues-the field faces to enable widespread deployment are discussed. How MNA design parameters can be exploited for controlled release of vaccines and immunotherapies, and the application to preclinical models of infection, cancer, autoimmunity, and allergies are explained. Specific strategies are also discussed to reduce off-target effects compared to conventional vaccine delivery routes, and novel chemical and manufacturing controls that enable cargo stability in MNAs across flexible intervals and temperatures. Clinical research using MNAs is then examined. Drawbacks of MNAs and the implications, and emerging opportunities to exploit MNAs for immune engineering and clinical use are concluded. 10.1002/adma.202302410
Transdermal drug delivery via microneedles to mediate wound microenvironment. Advanced drug delivery reviews Cutaneous wound healing is a complex process, while modulating the wound microenvironment has become an essential therapeutic goal. In clinics, advanced dressings or dermal templates can promote wound healing but their ability in mediating wound microenvironment is limited. In the last decade, microneedle (MN) array patches have emerged as a new class of wound dressings. These dressings enable non-invasive transdermal and precise medication delivery. Combined with smart materials, MN additionally allows real-time monitoring of wound site markers such as inflammatory factors, oxygen levels, vascularization, pH and temperature, etc., while releasing therapeutic molecules responsively to the wound site. In this review, the MN-based strategies were reviewed for modulating wound microenvironment via introducing the main characteristics of the wound microenvironment and various types of MN-based delivery systems. Additionally, the progress and future trends in the application of MNs in mediating wound microenvironments are also discussed. 10.1016/j.addr.2023.114753
Long-acting microneedle formulations. Advanced drug delivery reviews The minimally-invasive and painless nature of microneedle (MN) application has enabled the technology to obviate many issues with injectable drug delivery. MNs not only administer therapeutics directly into the dermal and ocular space, but they can also control the release profile of the active compound over a desired period. To enable prolonged delivery of payloads, various MN types have been proposed and evaluated, including dissolving MNs, polymeric MNs loaded or coated with nanoparticles, fast-separable MNs hollow MNs, and hydrogel MNs. These intricate yet intelligent delivery platforms provide an attractive approach to decrease side effects and administration frequency, thus offer the potential to increase patient compliance. In this review, MN formulations that are loaded with various therapeutics for long-acting delivery to address the clinical needs of a myriad of diseases are discussed. We also highlight the design aspects, such as polymer selection and MN geometry, in addition to computational and mathematical modeling of MNs that are necessary to help streamline and develop MNs with high translational value and clinical impact. Finally, up-scale manufacturing and regulatory hurdles along with potential avenues that require further research to bring MN technology to the market are carefully considered. It is hoped that this review will provide insight to formulators and clinicians that the judicious selection of materials in tandem with refined design may offer an elegant approach to achieve sustained delivery of payloads through the simple and painless application of a MN patch. 10.1016/j.addr.2023.115055
Microneedles for advanced ocular drug delivery. Advanced drug delivery reviews In the field of ocular drug delivery, topical delivery remains the most common treatment option for managing anterior segment diseases, whileintraocular injectionsare the current gold standard treatment option for treating posterior segment diseases. Nonetheless, topical eye drops are associated with low bioavailability (<5%), and theintravitreal administration procedure is highly invasive, yielding poor patient acceptability. In both cases, frequent administration is currently required. As a result, there is a clear unmet need for sustained drug delivery to the eye, particularly in a manner that can be localised. Microneedles, which are patches containing an array of micron-scale needles (<1 mm), have the potential to meet this need. These platforms can enable localised drug delivery to the eye while enhancing penetration of drug molecules through key ocular barriers, thereby improving overall therapeutic outcomes. Moreover, the minimally invasive manner in which microneedles are applied could provide significant advantages over traditional intravitreal injections regarding patient acceptability. Considering the benefitsofthis novel ocular delivery system, this review provides an in-depth overviewofthe microneedle systems for ocular drug delivery, including the types of microneedles used and therapeutics delivered. Notably, we outline and discuss the current challenges associated with the clinical translation of these platforms and offer opinions on factors which should be considered to improve such transition from lab to clinic. 10.1016/j.addr.2023.115082
Advances in Antimicrobial Microneedle Patches for Combating Infections. Jamaledin Rezvan,Yiu Cynthia K Y,Zare Ehsan N,Niu Li-Na,Vecchione Raffaele,Chen Guojun,Gu Zhen,Tay Franklin R,Makvandi Pooyan Advanced materials (Deerfield Beach, Fla.) Skin infections caused by bacteria, viruses and fungi are difficult to treat by conventional topical administration because of poor drug penetration across the stratum corneum. This results in low bioavailability of drugs to the infection site, as well as the lack of prolonged release. Emerging antimicrobial transdermal and ocular microneedle patches have become promising medical devices for the delivery of various antibacterial, antifungal, and antiviral therapeutics. In the present review, skin anatomy and its barriers along with skin infection are discussed. Potential strategies for designing antimicrobial microneedles and their targeted therapy are outlined. Finally, biosensing microneedle patches associated with personalized drug therapy and selective toxicity toward specific microbial species are discussed. 10.1002/adma.202002129