Showing papers in "Bioengineering & translational medicine in 2022"
TL;DR: In this article , the potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells.
Abstract: Abstract Urological cancers are among the most common malignancies around the world. In particular, bladder cancer severely threatens human health due to its aggressive and heterogeneous nature. Various therapeutic modalities have been considered for the treatment of bladder cancer although its prognosis remains unfavorable. It is perceived that treatment of bladder cancer depends on an interdisciplinary approach combining biology and engineering. The nanotechnological approaches have been introduced in the treatment of various cancers, especially bladder cancer. The current review aims to emphasize and highlight possible applications of nanomedicine in eradication of bladder tumor. Nanoparticles can improve efficacy of drugs in bladder cancer therapy through elevating their bioavailability. The potential of genetic tools such as siRNA and miRNA in gene expression regulation can be boosted using nanostructures by facilitating their internalization and accumulation at tumor sites and cells. Nanoparticles can provide photodynamic and photothermal therapy for ROS overgeneration and hyperthermia, respectively, in the suppression of bladder cancer. Furthermore, remodeling of tumor microenvironment and infiltration of immune cells for the purpose of immunotherapy are achieved through cargo‐loaded nanocarriers. Nanocarriers are mainly internalized in bladder tumor cells by endocytosis, and proper design of smart nanoparticles such as pH‐, redox‐, and light‐responsive nanocarriers is of importance for targeted tumor therapy. Bladder cancer biomarkers can be detected using nanoparticles for timely diagnosis of patients. Based on their accumulation at the tumor site, they can be employed for tumor imaging. The clinical translation and challenges are also covered in current review.
32 citations
TL;DR: In this paper , a systematic review of how nanoparticles (NPs) are used to enhance the radiotherapeutic effect, including preclinical and clinical studies, is presented.
Abstract: Improving the efficacy and spatial targeting of radiation therapy while sparing surrounding normal tissues has been a guiding principle for its use in cancer therapy. Nanotechnologies have shown considerable growth in terms of innovation and the development of new therapeutic approaches, particularly as radiosensitizers. The aim of this study was to systematically review how nanoparticles (NPs) are used to enhance the radiotherapeutic effect, including preclinical and clinical studies. Clinicaltrials.gov was used to perform the search using the following terms: radiation, cancer, and NPs. In this review, we describe the various designs of nano-radioenhancers, the rationale for using such technology, as well as their chemical and biological effects. Human trials are then discussed with an emphasis on their design and detailed clinical outcomes.
17 citations
TL;DR: This review gives an overview of FBR as well as anti‐FBR strategies, and highlights recent advances in biomimetic approaches to resist FBR, focusing on their characteristics and potential biomedical applications.
Abstract: Abstract Mitigating the foreign body response (FBR) to implantable medical devices (IMDs) is critical for successful long‐term clinical deployment. The FBR is an inevitable immunological reaction to IMDs, resulting in inflammation and subsequent fibrotic encapsulation. Excessive fibrosis may impair IMDs function, eventually necessitating retrieval or replacement for continued therapy. Therefore, understanding the implant design parameters and their degree of influence on FBR is pivotal to effective and long lasting IMDs. This review gives an overview of FBR as well as anti‐FBR strategies. Furthermore, we highlight recent advances in biomimetic approaches to resist FBR, focusing on their characteristics and potential biomedical applications.
16 citations
TL;DR: Histopathological evaluation of full‐thickness excisional wounds in BALB/c mice treated with mouse embryonic fibroblasts‐loaded nanofibrous scaffolds showed enhanced angiogenesis, and collagen synthesis as well as regeneration of the sebaceous glands and hair follicles in vivo.
Abstract: Abstract An ideal tissue‐engineered dermal substitute should possess angiogenesis potential to promote wound healing, antibacterial activity to relieve the bacterial burden on skin, as well as sufficient porosity for air and moisture exchange. In light of this, a glass–ceramic (GC) has been incorporated into chitosan and gelatin electrospun nanofibers (240–360 nm), which MEFs were loaded on it for healing acceleration. The GC was doped with silver to improve the antibacterial activity. The bioactive nanofibrous scaffolds demonstrated antibacterial and superior antibiofilm activities against Gram‐negative and Gram‐positive bacteria. The nanofibrous scaffolds were biocompatible, hemocompatible, and promoted cell attachment and proliferation. Nanofibrous skin substitutes with or without Ag‐doped GC nanoparticles did not induce an inflammatory response and attenuated LPS‐induced interleukin‐6 release by dendritic cells. The rate of biodegradation of the nanocomposite was similar to the rate of skin regeneration under in vivo conditions. Histopathological evaluation of full‐thickness excisional wounds in BALB/c mice treated with mouse embryonic fibroblasts‐loaded nanofibrous scaffolds showed enhanced angiogenesis, and collagen synthesis as well as regeneration of the sebaceous glands and hair follicles in vivo.
15 citations
TL;DR: The most recent advances of nanomaterials composite hydrogels in biomedicine, including drug and cell delivery, cancer treatment, tissue regeneration, biosensing, and bioimaging are discussed, and the current situation of their commoditization is discussed.
Abstract: Abstract Nanomaterials' unique structures at the nanometer level determine their incredible functions, and based on this, they can be widely used in the field of nanomedicine. However, nanomaterials do possess disadvantages that cannot be ignored, such as burst release, rapid elimination, and poor bioadhesion. Hydrogels are scaffolds with three‐dimensional structures, and they exhibit good biocompatibility and drug release capacity. Hydrogels are also associated with disadvantages for biomedical applications such as poor anti‐tumor capability, weak bioimaging capability, limited responsiveness, and so on. Incorporating nanomaterials into the 3D hydrogel network through physical or chemical covalent action may be an effective method to avoid their disadvantages. In nanocomposite hydrogel systems, multifunctional nanomaterials often work as the function core, giving the hydrogels a variety of properties (such as photo‐thermal conversion, magnetothermal conversion, conductivity, targeting tumor, etc.). While, hydrogels can effectively improve the retention effect of nanomaterials and make the nanoparticles have good plasticity to adapt to various biomedical applications (such as various biosensors). Nanocomposite hydrogel systems have broad application prospects in biomedicine. In this review, we comprehensively summarize and discuss the most recent advances of nanomaterials composite hydrogels in biomedicine, including drug and cell delivery, cancer treatment, tissue regeneration, biosensing, and bioimaging, and we also briefly discussed the current situation of their commoditization in biomedicine.
15 citations
TL;DR: In this article , a review of the application of chitosan-based nanoparticles for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P‐glycoprotein (P‐gp) to reverse drug resistance.
Abstract: Abstract Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS‐based nanoparticles (CS‐NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS‐NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P‐glycoprotein (P‐gp) to reverse drug resistance. These nanoarchitectures can provide co‐delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co‐loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid‐, carbon‐, polymeric‐ and metal‐based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS‐NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS‐NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH‐sensitive release of DOX can occur. Furthermore, redox‐ and light‐responsive CS‐NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS‐NPs, we expect to soon see significant progress towards clinical translation.
13 citations
TL;DR: In this paper , a review of the use of carbon-based nanoparticles in cardiac tissue engineering emphasizing their conductivity is presented, and the most commonly used conductive substrates comprising graphene, graphene oxide, carbon nanotubes, and carbon nanofibers in cardiac repair are studied.
Abstract: Abstract A proper self‐regenerating capability is lacking in human cardiac tissue which along with the alarming rate of deaths associated with cardiovascular disorders makes tissue engineering critical. Novel approaches are now being investigated in order to speedily overcome the challenges in this path. Tissue engineering has been revolutionized by the advent of nanomaterials, and later by the application of carbon‐based nanomaterials because of their exceptional variable functionality, conductivity, and mechanical properties. Electrically conductive biomaterials used as cell bearers provide the tissue with an appropriate microenvironment for the specific seeded cells as substrates for the sake of protecting cells in biological media against attacking mechanisms. Nevertheless, their advantages and shortcoming in view of cellular behavior, toxicity, and targeted delivery depend on the tissue in which they are implanted or being used as a scaffold. This review seeks to address, summarize, classify, conceptualize, and discuss the use of carbon‐based nanoparticles in cardiac tissue engineering emphasizing their conductivity. We considered electrical conductivity as a key affecting the regeneration of cells. Correspondingly, we reviewed conductive polymers used in tissue engineering and specifically in cardiac repair as key biomaterials with high efficiency. We comprehensively classified and discussed the advantages of using conductive biomaterials in cardiac tissue engineering. An overall review of the open literature on electroactive substrates including carbon‐based biomaterials over the last decade was provided, tabulated, and thoroughly discussed. The most commonly used conductive substrates comprising graphene, graphene oxide, carbon nanotubes, and carbon nanofibers in cardiac repair were studied.
13 citations
TL;DR: In this article , the authors discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection.
Abstract: Abstract Poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target‐specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane‐coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane‐camouflaged NPs.
13 citations
TL;DR: In this paper , the authors discuss how hydrogels can be designed for clinical translation, particularly in the context of the new European Medical Device Regulation (MDR), and suggest a framework for how academics can assist small and medium MedTech enterprises conducting the initial clinical investigation and post-market clinical follow-up required in the MDR.
Abstract: Musculoskeletal defects are an enormous healthcare burden and source of pain and disability for individuals. With an aging population, the proportion of individuals living with these medical indications will increase. Simultaneously, there is pressure on healthcare providers to source efficient solutions, which are cheaper and less invasive than conventional technology. This has led to an increased research focus on hydrogels as highly biocompatible biomaterials that can be delivered through minimally invasive procedures. This review will discuss how hydrogels can be designed for clinical translation, particularly in the context of the new European Medical Device Regulation (MDR). We will then do a deep dive into the clinically used hydrogel solutions that have been commercially approved or have undergone clinical trials in Europe or the United States. We will discuss the therapeutic mechanism and limitations of these products. Due to the vast application areas of hydrogels, this work focuses only on treatments of cartilage, bone, and the nucleus pulposus. Lastly, the main steps toward clinical translation of hydrogels as medical devices are outlined. We suggest a framework for how academics can assist small and medium MedTech enterprises conducting the initial clinical investigation and post-market clinical follow-up required in the MDR. It is evident that the successful translation of hydrogels is governed by acquiring high-quality pre-clinical and clinical data confirming the device mechanism of action and safety.
13 citations
TL;DR: A review on past and present therapeutic strategies for these two major neurodegenerative disorders in the clinical trial process can be found in this paper , highlighting the shift in clinical trials away from therapies targeting neurotransmitter systems that provide symptomatic relief, and towards antiaggregation, anti-inflammatory, antioxidant, and regeneration strategies that aim to inhibit the root causes of disease progression.
Abstract: Abstract Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent neurodegenerative diseases, affecting millions and costing billions each year in the United States alone. Despite tremendous progress in developing therapeutics that manage the symptoms of these two diseases, the scientific community has yet to develop a treatment that effectively slows down, inhibits, or cures neurodegeneration. To gain a better understanding of the current therapeutic frontier for the treatment of AD and PD, we provide a review on past and present therapeutic strategies for these two major neurodegenerative disorders in the clinical trial process. We briefly recap currently US Food and Drug Administration‐approved therapies, and then explore trends in clinical trials across the variables of therapy mechanism of disease intervention, administration route, use of delivery vehicle, and outcome measures, across the clinical phases over time for “Drug” and “Biologic” therapeutics. We then present the success rate of past clinical trials and analyze the intersections in therapeutic approaches for AD and PD, revealing the shift in clinical trials away from therapies targeting neurotransmitter systems that provide symptomatic relief, and towards anti‐aggregation, anti‐inflammatory, anti‐oxidant, and regeneration strategies that aim to inhibit the root causes of disease progression. We also highlight the evolving distribution of the types of “Biologic” therapies investigated, and the slowly increasing yet still severe under‐utilization of delivery vehicles for AD and PD therapeutics. We then briefly discuss novel preclinical strategies for treating AD and PD. Overall, this review aims to provide a succinct overview of the clinical landscape of AD and PD therapies to better understand the field's therapeutic strategy in the past and the field's evolution in approach to the present, to better inform how to effectively treat AD and PD in the future.
12 citations
TL;DR: All aspects of wet adhesion of Mytilidae mussels, as well as different strategies needed for designing and fabricating wet adhesives are discussed from a chemistry point of view.
Abstract: Abstract After several billions of years, nature still makes decisions on its own to identify, develop, and direct the most effective material for phenomena/challenges faced. Likewise, and inspired by the nature, we learned how to take steps in developing new technologies and materials innovations. Wet and strong adhesion by Mytilidae mussels (among which Mytilus edulis —blue mussel and Mytilus californianus —California mussel are the most well‐known species) has been an inspiration in developing advanced adhesives for the moist condition. The wet adhesion phenomenon is significant in designing tissue adhesives and surgical sealants. However, a deep understanding of engaged chemical moieties, microenvironmental conditions of secreted proteins, and other contributing mechanisms for outstanding wet adhesion mussels are essential for the optimal design of wet glues. In this review, all aspects of wet adhesion of Mytilidae mussels, as well as different strategies needed for designing and fabricating wet adhesives are discussed from a chemistry point of view. Developed muscle‐inspired chemistry is a versatile technique when designing not only wet adhesive, but also, in several more applications, especially in the bioengineering area. The applications of muscle‐inspired biomaterials in various medical applications are summarized for future developments in the field.
TL;DR: This study provides an effective strategy for skin repair through the combination of the novel robot and a bioactive bioink, and has a promising clinical translational potential for further applications.
Abstract: Abstract Skin acts as an essential barrier, protecting organisms from their environment. For skin trauma caused by accidental injuries, rapid healing, personalization, and functionality are vital requirements in clinical, which are the bottlenecks hindering the translation of skin repair from benchside to bedside. Herein, we described a novel design and a proof‐of‐concept demonstration of an adaptive bioprinting robot to proceed rapid in situ bioprinting on a full‐thickness excisional wound in mice. The three‐dimensional (3D) scanning and closed‐loop visual system integrated in the robot and the multi‐degree‐of‐freedom mechanism provide immediate, precise, and complete wound coverage through stereotactic bioprinting, which hits the key requirements of rapid‐healing and personalization in skin repair. Combined with the robot, epidermal stem cells and skin‐derived precursors isolated from neonatal mice mixed with Matrigel were directly printed into the injured area to replicate the skin structure. Excisional wounds after bioprinting showed complete wound healing and functional skin tissue regeneration that closely resembling native skin, including epidermis, dermis, blood vessels, hair follicles and sebaceous glands etc. This study provides an effective strategy for skin repair through the combination of the novel robot and a bioactive bioink, and has a promising clinical translational potential for further applications.
TL;DR: This review attempts to discuss the advantages and challenges of portable hand‐held bioprinters via in situ tissue regeneration, including skin, cartilage, bone, dental, and skeletal muscle regeneration, while the tissues that could be regenerated via this approach are targeted in the authors' perspective.
Abstract: Abstract Three‐dimensional bioprinting, as a novel technique of fabricating engineered tissues, is positively correlated with the ultimate goal of regenerative medicine, which is the restoration, reconstruction, and repair of lost and/or damaged tissue function. The progressive trend of this technology resulted in developing the portable hand‐held bioprinters, which could be used quite easily by surgeons and physicians. With the advent of portable hand‐held bioprinters, the obstacles and challenges of utilizing statistical bioprinters could be resolved. This review attempts to discuss the advantages and challenges of portable hand‐held bioprinters via in situ tissue regeneration. All the tissues that have been investigated by this approach were reviewed, including skin, cartilage, bone, dental, and skeletal muscle regeneration, while the tissues that could be regenerated via this approach are targeted in the authors' perspective. The design and applications of hand‐held bioprinters were discussed widely, and the marketed printers were introduced. It has been prospected that these facilities could ameliorate translating the regenerative medicine science from the bench to the bedside actively.
TL;DR: This article reviews nucleic acid‐ and antigen–antibody‐based serological assays, and compares the performance of some of the most recent FDA‐approved and literature‐reported assays and associated kits for the specific testing of new coronavirus variants.
Abstract: Abstract The World Health Organization has reported approximately 430 million confirmed cases of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), worldwide, including nearly 6 million deaths, since its initial appearance in China in 2019. While the number of diagnosed cases continues to increase, the need for technologies that can accurately and rapidly detect SARS‐CoV‐2 virus infection at early phases continues to grow, and the Federal Drug Administration (FDA) has licensed emergency use authorizations (EUAs) for virtually hundreds of diagnostic tests based on nucleic acid molecules and antigen–antibody serology assays. Among them, the quantitative real‐time reverse transcription PCR (qRT‐PCR) assay is considered the gold standard for early phase virus detection. Unfortunately, qRT‐PCR still suffers from disadvantages such as the complex test process and the occurrence of false negatives; therefore, new nucleic acid detection devices and serological testing technologies are being developed. However, because of the emergence of strongly infectious mutants of the new coronavirus, such as Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529), the need for the specific detection of mutant strains is also increasing. Therefore, this article reviews nucleic acid‐ and antigen–antibody‐based serological assays, and compares the performance of some of the most recent FDA‐approved and literature‐reported assays and associated kits for the specific testing of new coronavirus variants.
TL;DR: An overview of the current clinically relevant RNA therapeutics, mechanistic basis of their function, and strategies to improve their clinical use is provided, with an emphasis on their respective mechanisms and disease areas.
Abstract: Abstract Ribonucleic acid (RNA) therapeutics are being actively researched as a therapeutic modality in preclinical and clinical studies. They have become one of the most ubiquitously known and discussed therapeutics in recent years in part due to the ongoing coronavirus pandemic. Since the first approval in 1998, research on RNA therapeutics has progressed to discovering new therapeutic targets and delivery strategies to enhance their safety and efficacy. Here, we provide an overview of the current clinically relevant RNA therapeutics, mechanistic basis of their function, and strategies to improve their clinical use. We discuss the 17 approved RNA therapeutics and perform an in‐depth analysis of the 222 ongoing clinical trials, with an emphasis on their respective mechanisms and disease areas. We also provide perspectives on the challenges for clinical translation of RNA therapeutics and suggest potential strategies to address these challenges.
TL;DR: In this paper , a fiber-reinforced porous scaffold was developed based on aptamer Apt19S-mediated mesenchymal stem cell (MSC)-specific recruitment and dual growth factor (GF)-enhanced meniscal differentiation.
Abstract: Reconstruction of the knee meniscus remains a significant clinical challenge owing to its complex anisotropic tissue organization, complex functions, and limited healing capacity in the inner region. The development of in situ tissue-engineered meniscal scaffolds, which provide biochemical signaling to direct endogenous stem/progenitor cell (ESPC) behavior, has the potential to revolutionize meniscal tissue engineering. In this study, a fiber-reinforced porous scaffold was developed based on aptamer Apt19S-mediated mesenchymal stem cell (MSC)-specific recruitment and dual growth factor (GF)-enhanced meniscal differentiation. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized meniscus extracellular matrix (MECM) and then mixed with gelatin methacrylate (GelMA) to form a photocrosslinkable hydrogel. Second, connective tissue growth factor (CTGF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and transforming growth factor-β3 (TGF-β3)-loaded PLGA microparticles (MPs) were mixed with aptamer-conjugated MECM to simulate anisotropic meniscal regeneration. These three bioactive molecules were delivered sequentially. Apt19S, which exhibited high binding affinity to synovium-derived MSCs (SMSCs), was quickly released to facilitate the mobilization of ESPCs. CTGF incorporated within PLGA NPs was released rapidly, inducing profibrogenic differentiation, while sustained release of TGF-β3 in PLGA MPs remodeled the fibrous matrix into fibrocartilaginous matrix. The in vitro results showed that the sequential release of Apt19S/GFs promoted cell migration, proliferation, and fibrocartilaginous differentiation. The in vivo results demonstrated that the sequential release system of Apt/GF-scaffolds increased neomeniscal formation in rabbit critical-sized meniscectomies. Thus, the novel delivery system shows potential for guiding meniscal regeneration in situ.
TL;DR: This review provides an overview of existing and potential nanomaterial‐based biosensors that can be used for rapid SARS‐CoV‐2 diagnostics and holds immense potential for rapid coronavirus detection because of their noninvasive and susceptible, as well as selective properties that have the potential to give real‐time results at an economical cost.
Abstract: Abstract With the threat of increasing SARS‐CoV‐2 cases looming in front of us and no effective and safest vaccine available to curb this pandemic disease due to its sprouting variants, many countries have undergone a lockdown 2.0 or planning a lockdown 3.0. This has upstretched an unprecedented demand to develop rapid, sensitive, and highly selective diagnostic devices that can quickly detect coronavirus (COVID‐19). Traditional techniques like polymerase chain reaction have proven to be time‐inefficient, expensive, labor intensive, and impracticable in remote settings. This shifts the attention to alternative biosensing devices that can be successfully used to sense the COVID‐19 infection and curb the spread of coronavirus cases. Among these, nanomaterial‐based biosensors hold immense potential for rapid coronavirus detection because of their noninvasive and susceptible, as well as selective properties that have the potential to give real‐time results at an economical cost. These diagnostic devices can be used for mass COVID‐19 detection to understand the rapid progression of the infection and give better‐suited therapies. This review provides an overview of existing and potential nanomaterial‐based biosensors that can be used for rapid SARS‐CoV‐2 diagnostics. Novel biosensors employing different detection mechanisms are also highlighted in different sections of this review. Practical tools and techniques required to develop such biosensors to make them reliable and portable have also been discussed in the article. Finally, the review is concluded by presenting the current challenges and future perspectives of nanomaterial‐based biosensors in SARS‐CoV‐2 diagnostics.
TL;DR: In this paper , the authors discuss the diverse roles of miRNAs in various stages of wound healing and provide an insight on the most recent findings in the nanotechnology and biomaterials field, which might offer opportunities for the development of new strategies for this chronic condition.
Abstract: Abstract MicroRNAs (miRNAs) as therapeutic agents have attracted increasing interest in the past decade owing to their significant effectiveness in treating a wide array of ailments. These polymerases II‐derived noncoding RNAs act through post‐transcriptional controlling of different proteins and their allied pathways. Like other areas of medicine, researchers have utilized miRNAs for managing acute and chronic wounds. The increase in the number of patients suffering from either under‐healing or over‐healing wound demonstrates the limited efficacy of the current wound healing strategies and dictates the demands for simpler approaches with greater efficacy. Various miRNA can be designed to induce pathway beneficial for wound healing. However, the proper design of miRNA and its delivery system for wound healing applications are still challenging due to their limited stability and intracellular delivery. Therefore, new miRNAs are required to be identified and their delivery strategy needs to be optimized. In this review, we discuss the diverse roles of miRNAs in various stages of wound healing and provide an insight on the most recent findings in the nanotechnology and biomaterials field, which might offer opportunities for the development of new strategies for this chronic condition. We also highlight the advances in biomaterials and delivery systems, emphasizing their challenges and resolutions for miRNA‐based wound healing. We further review various biovectors (e.g., adenovirus and lentivirus) and abiotic materials such as organic and inorganic nanomaterials, along with dendrimers and scaffolds, as the delivery systems for miRNA‐based wound healing. Finally, challenges and opportunities for translation of miRNA‐based strategies into clinical applications are discussed.
TL;DR: The in vivo results demonstrated that the sequential release system of Apt/GF‐scaffolds increased neomeniscal formation in rabbit critical‐sized meniscectomies, and the novel delivery system shows potential for guiding meniscal regeneration in situ.
Abstract: Abstract Reconstruction of the knee meniscus remains a significant clinical challenge owing to its complex anisotropic tissue organization, complex functions, and limited healing capacity in the inner region. The development of in situ tissue‐engineered meniscal scaffolds, which provide biochemical signaling to direct endogenous stem/progenitor cell (ESPC) behavior, has the potential to revolutionize meniscal tissue engineering. In this study, a fiber‐reinforced porous scaffold was developed based on aptamer Apt19S‐mediated mesenchymal stem cell (MSC)‐specific recruitment and dual growth factor (GF)‐enhanced meniscal differentiation. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized meniscus extracellular matrix (MECM) and then mixed with gelatin methacrylate (GelMA) to form a photocrosslinkable hydrogel. Second, connective tissue growth factor (CTGF)‐loaded poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) and transforming growth factor‐β3 (TGF‐β3)‐loaded PLGA microparticles (MPs) were mixed with aptamer‐conjugated MECM to simulate anisotropic meniscal regeneration. These three bioactive molecules were delivered sequentially. Apt19S, which exhibited high binding affinity to synovium‐derived MSCs (SMSCs), was quickly released to facilitate the mobilization of ESPCs. CTGF incorporated within PLGA NPs was released rapidly, inducing profibrogenic differentiation, while sustained release of TGF‐β3 in PLGA MPs remodeled the fibrous matrix into fibrocartilaginous matrix. The in vitro results showed that the sequential release of Apt19S/GFs promoted cell migration, proliferation, and fibrocartilaginous differentiation. The in vivo results demonstrated that the sequential release system of Apt/GF‐scaffolds increased neomeniscal formation in rabbit critical‐sized meniscectomies. Thus, the novel delivery system shows potential for guiding meniscal regeneration in situ.
TL;DR: Alkaline phosphate activity and alizarin red staining results indicate that the dECM‐based biocomposite exhibit significantly higher osteogenic activities, including calcification, compared to the collagen‐basedBiocomposites.
Abstract: Abstract The goal of this study was to fabricate bioactive cell‐laden biocomposites supplemented with bone‐derived decellularized extracellular matrix (dECM) with calcium phosphate ceramic, and to assess the effect of the biocomponents on the osteogenic and odontogenic differentiation of human dental pulp stem cells (hDPSCs). By evaluating the rheological properties and selecting printing parameters, mechanically stable cell‐laden 3D biocomposites with high initial cell‐viability (>90%) and reasonable printability (≈0.9) were manufactured. The cytotoxicity of the biocomposites was evaluated via MTT assay and nuclei/F‐actin fluorescent analyses, while the osteo/odontogenic differentiation of the hDPSCs was assessed using histological and immunofluorescent analyses and various gene expressions. Alkaline phosphate activity and alizarin red staining results indicate that the dECM‐based biocomposites exhibit significantly higher osteogenic activities, including calcification, compared to the collagen‐based biocomposites. Furthermore, immunofluorescence images and gene expressions demonstrated upregulation of dentin matrix acidic phosphoprotein‐1 and dentin sialophosphoprotein in the dECM‐based biocomposites, indicating acceleration of the odontogenic differentiation of hDPSCs in the printed biocomposites. The hDPSC‐laden biocomposite was implanted into the subcutaneous region of mice, and the biocomposite afforded clear induction of osteo/odontogenic ectopic hard tissue formation 8 weeks post‐transplantation. From these results, we suggest that the hDPSC‐laden biocomposite is a promising biomaterial for dental tissue engineering.
TL;DR: It is suggested that local NTP therapy stimulates systemic, anti‐cancer immunity, and enhances the cancer‐immunity cycle, as immune cells in both the tumor and tumor‐draining lymph nodes appear more stimulated to perform their anti-cancer functions.
Abstract: Abstract Melanoma remains a deadly cancer despite significant advances in immune checkpoint blockade and targeted therapies. The incidence of melanoma is also growing worldwide, which highlights the need for novel treatment options and strategic combination of therapies. Here, we investigate non‐thermal plasma (NTP), an ionized gas, as a promising, therapeutic option. In a melanoma mouse model, direct treatment of tumors with NTP results in reduced tumor burden and prolonged survival. Physical characterization of NTP treatment in situ reveals the deposited NTP energy and temperature associated with therapy response, and whole transcriptome analysis of the tumor identified several modulated pathways. NTP treatment also enhances the cancer‐immunity cycle, as immune cells in both the tumor and tumor‐draining lymph nodes appear more stimulated to perform their anti‐cancer functions. Thus, our data suggest that local NTP therapy stimulates systemic, anti‐cancer immunity. We discuss, in detail, how these fundamental insights will help direct the translation of NTP technology into the clinic and inform rational combination strategies to address the challenges in melanoma therapy.
TL;DR: In this article , the authors developed a high-throughput biomimetic bone-on-a-chip platform combined with an artificial intelligence (AI)based image analysis system.
Abstract: Abstract Although numerous organ‐on‐a‐chips have been developed, bone‐on‐a‐chip platforms have rarely been reported because of the high complexity of the bone microenvironment. With an increase in the elderly population, a high‐risk group for bone‐related diseases such as osteoporosis, it is essential to develop a precise bone‐mimicking model for efficient drug screening and accurate evaluation in preclinical studies. Here, we developed a high‐throughput biomimetic bone‐on‐a‐chip platform combined with an artificial intelligence (AI)‐based image analysis system. To recapitulate the key aspects of natural bone microenvironment, mouse osteocytes (IDG‐SW3) and osteoblasts (MC3T3‐E1) were cocultured within the osteoblast‐derived decellularized extracellular matrix (OB‐dECM) built in a well plate‐based three‐dimensional gel unit. This platform spatiotemporally and configurationally mimics the characteristics of the structural bone unit, known as the osteon. Combinations of native and bioactive ingredients obtained from the OB‐dECM and coculture of two types of bone cells synergistically enhanced osteogenic functions such as osteocyte differentiation and osteoblast maturation. This platform provides a uniform and transparent imaging window that facilitates the observation of cell–cell interactions and features high‐throughput bone units in a well plate that is compatible with a high‐content screening system, enabling fast and easy drug tests. The drug efficacy of anti‐SOST antibody, which is a newly developed osteoporosis drug for bone formation, was tested via β‐catenin translocation analysis, and the performance of the platform was evaluated using AI‐based deep learning analysis. This platform could be a cutting‐edge translational tool for bone‐related diseases and an efficient alternative to bone models for the development of promising drugs.
TL;DR: The evidence of a role of the MGB axis in epilepsy is summarized by providing an overview of the recent clinical and preclinical studies and showing how dietary modification, microbiome supplementations, and hence, microbiota alterations may have an impact on seizures.
Abstract: Abstract Epilepsy is a common neurological disease characterized by the enduring predisposition of the brain to generate seizures. Among the recognized causes, a role played by the gut microbiota in epilepsy has been hypothesized and supported by new investigative approaches. To dissect the microbiota‐gut‐brain (MGB) axis involvement in epilepsy, in vitro modeling approaches arouse interest among researchers in the field. This review summarizes, first of all, the evidence of a role of the MGB axis in epilepsy by providing an overview of the recent clinical and preclinical studies and showing how dietary modification, microbiome supplementations, and hence, microbiota alterations may have an impact on seizures. Subsequently, the currently available strategies to study epilepsy on animal and in vitro models are described, focusing attention on these latter and the technological challenges for integration with already existing MGB axis models. Finally, the implementation of existing epilepsy in vitro systems is discussed, offering a complete overview of the available technological tools which may improve reliability and clinical translation of the results towards the development of innovative therapeutic approaches, taking advantage of complementary technologies.
TL;DR: This modality could promote skin wound healing and effectively suppress scar formation in the preclinical murine skin wounds and the cytomembrane biologics might provide a biocompatible and versatile tool for wound healing.
Abstract: Abstract Effective skin wound healing is a complex process involving anti‐inflammation, fibrosis, matrix reconstruction, and angiogenesis. This work aimed to integrate the macrophage‐mediated anti‐inflammation and fibroblast‐assisted matrix reconstruction for enhanced skin wound healing. Herein, we utilized the cytomembranes derived from repolarized M2 macrophages and fibroblasts to prepare the natural biologics. Results showed that the inflammatory M1 macrophages were repolarized to M2 phenotype by the M2 macrophage cytomembranes. As a consequence, the cytomembranes of M2 macrophage could facilitate the wound closure in mice. Furthermore, the addition of fibroblast membranes to the macrophage cytomembranes contributed to a better matrix reconstruction, neovascularization and angiogenesis. Next, we used a transforming growth factor‐β (TGF‐β) inhibitor to attenuate cutaneous scar formation. Therefore, our modality could promote skin wound healing and effectively suppress scar formation in the preclinical murine skin wounds. The cytomembrane biologics might provide a biocompatible and versatile tool for wound healing.
TL;DR: Wang et al. as discussed by the authors showed that methyl-CpG-binding protein 2 (MECP2), a protein responsible for the interpretation of DNA methylome-encoded information, was abnormally expressed in lung and bronchoalveolar lavage fluid samples of IPF patients and mice with onset of pulmonary fibrosis.
Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by the infiltration of macrophages in the fibrotic region. Currently, no therapeutic strategies effectively control disease progression, and the 5-year mortality of patients after diagnosis is unacceptably high. Thus, developing an effective and safe treatment for IPF is urgently needed. The present study illustrated that methyl-CpG-binding protein 2 (MECP2), a protein responsible for the interpretation of DNA methylome-encoded information, was abnormally expressed in lung and bronchoalveolar lavage fluid samples of IPF patients and mice with onset of pulmonary fibrosis. And further studies verified that the overexpression of MECP2 occurred mainly in macrophages. Inhibition of Mecp2 expression in macrophages robustly abrogated alternatively activated macrophage (M2) polarization by regulating interferon regulatory factor 4 expression. Accordingly, cationic liposomes loading Mecp2 small interfering RNA (siRNA) were raised for the treatment of pulmonary fibrosis. It was noted that the liposomes accumulated in the fibrotic region after intratracheal injection, especially in macrophages. In addition, intratracheal administration of Mecp2 siRNA-loaded liposomes significantly reversed the established pulmonary fibrosis with few side-effects and high safety coefficients. Collectively, these results are essential not only for further understanding the DNA methylation in pathogenesis of IPF but also for providing a potent therapeutic strategy for IPF treatment in the clinic practice.
TL;DR: In this paper , a single intravitreal injection of poly(lactide-co-glycolide) icariin in a rat model of anterior ischemic optic neuropathy (rAION) was evaluated.
Abstract: An ischemic insult at optic nerve (ON) is followed by detrimental neuroinflammation that results in progressive and long-lasting retinal ganglion cell (RGC) death and vision loss. Icariin was reported to be a safe and effective natural anti-inflammatory drug. Herein, we evaluated the long-term therapeutic effects of a single intravitreal injection of poly(lactide-co-glycolide) PLGA-icariin in a rat model of anterior ischemic optic neuropathy (rAION). Treatment with PLGA microspheres of icariin preserved the visual function and RGC density for 1 month in the rAION model. In addition, ON edema and macrophage infiltration were inhibited by treating PLGA microspheres of icariin. We found that the binding complex of icariin and CCAAT enhancer binding protein beta (CEBP-β) significantly induced endogenous granulocyte colony-stimulating factor (G-CSF) expression to activate noncanonical nuclear factor kappa B (NF-κB) signaling pathway by promoting an alternative phosphorylation reaction of IKK-β. Activation of noncanonical NF-κB signaling pathway promoted the M2 microglia/macrophage polarization and AKT1 activation, which prevented neuroinflammation and RGC apoptosis after ON infarct. This study concluded that protective mechanism of icariin is a CEBP-β/G-CSF axis-induced noncanonical NF-κB activation, which provides the long-term neuroprotective effects via anti-inflammatory and antiapoptotic actions after ON ischemia.
TL;DR: In this article , a bird's eye view on the latest development and application of 3D bioprinting in the regeneration of the skeletal muscle tissues and their application in restoring the functional abilities of the damaged craniofacial tissue.
Abstract: Abstract Anatomical complications of the craniofacial regions often present considerable challenges to the surgical repair or replacement of the damaged tissues. Surgical repair has its own set of limitations, including scarcity of the donor tissues, immune rejection, use of immune suppressors followed by the surgery, and restriction in restoring the natural aesthetic appeal. Rapid advancement in the field of biomaterials, cell biology, and engineering has helped scientists to create cellularized skeletal muscle‐like structures. However, the existing method still has limitations in building large, highly vascular tissue with clinical application. With the advance in the three‐dimensional (3D) bioprinting technique, scientists and clinicians now can produce the functional implants of skeletal muscles and bones that are more patient‐specific with the perfect match to the architecture of their craniofacial defects. Craniofacial tissue regeneration using 3D bioprinting can manage and eliminate the restrictions of the surgical transplant from the donor site. The concept of creating the new functional tissue, exactly mimicking the anatomical and physiological function of the damaged tissue, looks highly attractive. This is crucial to reduce the donor site morbidity and retain the esthetics. 3D bioprinting can integrate all three essential components of tissue engineering, that is, rehabilitation, reconstruction, and regeneration of the lost craniofacial tissues. Such integration essentially helps to develop the patient‐specific treatment plans and damage site‐driven creation of the functional implants for the craniofacial defects. This article is the bird's eye view on the latest development and application of 3D bioprinting in the regeneration of the skeletal muscle tissues and their application in restoring the functional abilities of the damaged craniofacial tissue. We also discussed current challenges in craniofacial bone vascularization and gave our view on the future direction, including establishing the interactions between tissue‐engineered skeletal muscle and the peripheral nervous system.
TL;DR: In this paper , the effects of biophysical signals such as surface topography, mechanical, and electrical signals on cell fate decisions are summarized and compared to the role of biochemical factors in tissue engineering.
Abstract: Abstract Tissue engineering (TE) is currently considered a cutting‐edge discipline that offers the potential for developing treatments for health conditions that negatively affect the quality of life. This interdisciplinary field typically involves the combination of cells, scaffolds, and appropriate induction factors for the regeneration and repair of damaged tissue. Cell fate decisions, such as survival, proliferation, or differentiation, critically depend on various biochemical and biophysical factors provided by the extracellular environment during developmental, physiological, and pathological processes. Therefore, understanding the mechanisms of action of these factors is critical to accurately mimic the complex architecture of the extracellular environment of living tissues and improve the efficiency of TE approaches. In this review, we recapitulate the effects that biochemical and biophysical induction factors have on various aspects of cell fate. While the role of biochemical factors, such as growth factors, small molecules, extracellular matrix (ECM) components, and cytokines, has been extensively studied in the context of TE applications, it is only recently that we have begun to understand the effects of biophysical signals such as surface topography, mechanical, and electrical signals. These biophysical cues could provide a more robust set of stimuli to manipulate cell signaling pathways during the formation of the engineered tissue. Furthermore, the simultaneous application of different types of signals appears to elicit synergistic responses that are likely to improve functional outcomes, which could help translate results into successful clinical therapies in the future.
TL;DR: In this paper , the recombinant integrant probiotic strain Escherichia coli Nissle 1917 (EcN) was used to create a strain EcN-GLP-1 that effectively delivers the heterologous GLP-like peptide-1 molecule.
Abstract: Considerable evidence suggests that insulin resistance is closely linked to Parkinson's disease (PD), leading to agents aiming at treating diabetes can be regarded as new neuroprotective strategies in PD, notably glucagon-like peptide-1 (GLP-1). However, the extremely short half-life of GLP-1 due to degradation by the ubiquitous proteolytic enzyme limits its clinical application. In this study, we engineered the recombinant integrant probiotic strain Escherichia coli Nissle 1917 (EcN) to create a strain EcN-GLP-1 that effectively delivers the heterologous GLP-1 molecule. Subsequently, we assessed its neuroprotective effects on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. We demonstrated that EcN-GLP-1 treatment could improve motor deficits, increase tyrosine hydroxylase-positive neurons, suppress microglia and astrocyte activation, reduce brain and colon inflammation, and ameliorate colonic barrier function damaged by MPTP induction. Meanwhile, we confirmed that the oral administration of EcN-GLP-1 could restore the disturbance of gut microbiota in the MPTP-induced PD mice, by reducing the relative abundances of Akkermansia and Oscillospira, and increasing the level of Prevotella in the gut. These results support further development of an engineered probiotic platform in which production of GLP-1 for gut-brain disorders, such as PD.
TL;DR: Novel polycaprolactone‐based polyurethane (PCL‐PU) copolymers with hyperelasticity, shape‐memory, and ultra‐cell‐adhesion properties are reported as clinically applicable tissue‐regenerative biomaterials.
Abstract: Abstract Novel polycaprolactone‐based polyurethane (PCL‐PU) copolymers with hyperelasticity, shape‐memory, and ultra‐cell‐adhesion properties are reported as clinically applicable tissue‐regenerative biomaterials. New isosorbide derivatives (propoxylated or ethoxylated ones) were developed to improve mechanical properties by enhanced reactivity in copolymer synthesis compared to the original isosorbide. Optimized PCL‐PU with propoxylated isosorbide exhibited notable mechanical performance (50 MPa tensile strength and 1150% elongation with hyperelasticity under cyclic load). The shape‐memory effect was also revealed in different forms (film, thread, and 3D scaffold) with 40%–80% recovery in tension or compression mode after plastic deformation. The ultra‐cell‐adhesive property was proven in various cell types which were reasoned to involve the heat shock protein‐mediated integrin (α5 and αV) activation, as analyzed by RNA sequencing and inhibition tests. After the tissue regenerative potential (muscle and bone) was confirmed by the myogenic and osteogenic responses in vitro, biodegradability, compatible in vivo tissue response, and healing capacity were investigated with in vivo shape‐memorable behavior. The currently exploited PCL‐PU, with its multifunctional (hyperelastic, shape‐memorable, ultra‐cell‐adhesive, and degradable) nature and biocompatibility, is considered a potential tissue‐regenerative biomaterial, especially for minimally invasive surgery that requires small incisions to approach large defects with excellent regeneration capacity.