BME frontiers最新文献

The interest in using therapeutic nanoparticles to bind with harmful molecules or pathogens and subsequently neutralize their bioactivity has grown tremendously. Among various nanomedicine platforms, cell membrane-coated nanoparticles, namely, "cellular nanosponges," stand out for their broad-spectrum neutralization capability challenging to achieve in traditional countermeasure technologies. Such ability is attributable to their cellular function-based rather than target structure-based working principle. Integrating cellular nanosponges with various synthetic substrates further makes their applications exceptionally versatile and adaptive. This review discusses the latest cellular nanosponge technology focusing on how the structure-function relationship in different designs has led to versatile and potent medical countermeasures. Four design strategies are discussed, including harnessing native cell membrane functions for biological neutralization, functionalizing cell membrane coatings to enhance neutralization capabilities, combining cell membranes and functional cores for multimodal neutralization, and integrating cellular nanosponges with hydrogels for localized applications. Examples in each design strategy are selected, and the discussion is to highlight their structure-function relationships in complex disease settings. The review may inspire additional design strategies for cellular nanosponges and fulfill even broader medical applications.

Treatments for disease in the central nervous system (CNS) are limited because of difficulties in agent penetration through the blood-brain barrier, achieving optimal dosing, and mitigating off-target effects. The prospect of precision medicine in CNS treatment suggests an opportunity for therapeutic nanotechnology, which offers tunability and adaptability to address specific diseases as well as targetability when combined with antibodies (Abs). Here, we review the strategies to attach Abs to nanoparticles (NPs), including conventional approaches of chemisorption and physisorption as well as attempts to combine irreversible Ab immobilization with controlled orientation. We also summarize trends that have been observed through studies of systemically delivered Ab-NP conjugates in animals. Finally, we discuss the future outlook for Ab-NPs to deliver therapeutics into the CNS.

[This corrects the article DOI: 10.34133/2022/9765307.].

The effective treatment of patients with cancer hinges on the delivery of therapeutics to a tumor site. Nanoparticles provide an essential transport system. We present 5 principles to consider when designing nanoparticles for cancer targeting: (a) Nanoparticles acquire biological identity in vivo, (b) organs compete for nanoparticles in circulation, (c) nanoparticles must enter solid tumors to target tumor components, (d) nanoparticles must navigate the tumor microenvironment for cellular or organelle targeting, and (e) size, shape, surface chemistry, and other physicochemical properties of nanoparticles influence their transport process to the target. This review article describes these principles and their application for engineering nanoparticle delivery systems to carry therapeutics to tumors or other disease targets.

Objective: A protein-based leaking-proof theranostic nanoplatform for dual-modality imaging-guided tumor photodynamic therapy (PDT) has been designed. Impact Statement: A site-specific conjugation of chlorin e6 (Ce6) to ferrimagnetic ferritin (MFtn-Ce6) has been constructed to address the challenge of unexpected leakage that often occurs during small-molecule drug delivery. Introduction: PDT is one of the most promising approaches for tumor treatment, while a delivery system is typically required for hydrophobic photosensitizers. However, the nonspecific distribution and leakage of photosensitizers could lead to insufficient drug accumulation in tumor sites. Methods: An engineered ferritin was generated for site-specific conjugation of Ce6 to obtain a leaking-proof delivery system, and a ferrimagnetic core was biomineralized in the cavity of ferritin, resulting in a fluorescent ferrimagnetic ferritin nanoplatform (MFtn-Ce6). The distribution and tumor targeting of MFtn-Ce6 can be detected by magnetic resonance imaging (MRI) and fluorescence imaging (FLI). Results: MFtn-Ce6 showed effective dual-modality MRI and FLI. A prolonged in vivo circulation and increased tumor accumulation and retention of photosensitizer was observed. The time-dependent distribution of MFtn-Ce6 can be precisely tracked in real time to find the optimal time window for PDT treatment. The colocalization of ferritin and the iron oxide core confirms the high stability of the nanoplatform in vivo. The results showed that mice treated with MFtn-Ce6 exhibited marked tumor-suppressive activity after laser irradiation. Conclusion: The ferritin-based leaking-proof nanoplatform can be used for the efficient delivery of the photosensitizer to achieve an enhanced therapeutic effect. This method established a general approach for the dual-modality imaging-guided tumor delivery of PDT agents.

[This corrects the article DOI: 10.34133/bmef.0004.].

Craniofacial reconstruction requires robust bone of specified geometry for the repair to be both functional and aesthetic. While native bone from elsewhere in the body can be harvested, shaped, and implanted within a defect, using either an in vitro or in vivo bioreactors eliminates donor site morbidity while increasing the customizability of the generated tissue. In vitro bioreactors utilize cells harvested from the patient, a scaffold, and a device to increase mass transfer of nutrients, oxygen, and waste, allowing for generation of larger viable tissues. In vivo bioreactors utilize the patient's own body as a source of cells and of nutrient transfer and involve the implantation of a scaffold with or without growth factors adjacent to vasculature, followed by the eventual transfer of vascularized, mineralized tissue to the defect site. Several different models of in vitro bioreactors exist, and several different implantation sites have been successfully utilized for in vivo tissue generation and defect repair in humans. In this review, we discuss the specifics of each bioreactor strategy, as well as the advantages and disadvantages of each and the future directions for the engineering of bony tissues for craniofacial defect repair.

If the 20th century was the age of mapping and controlling the external world, the 21st century is the biomedical age of mapping and controlling the biological internal world. The biomedical age is bringing new technological breakthroughs for sensing and controlling human biomolecules, cells, tissues, and organs, which underpin new frontiers in the biomedical discovery, data, biomanufacturing, and translational sciences. This article reviews what we believe will be the next wave of biomedical engineering (BME) education in support of the biomedical age, what we have termed BME 2.0. BME 2.0 was announced on October 12 2017 at BMES 49 (https://www.bme.jhu.edu/news-events/news/miller-opens-2017-bmes-annual-meeting-with-vision-for-new-bme-era/). We present several principles upon which we believe the BME 2.0 curriculum should be constructed, and from these principles, we describe what view as the foundations that form the next generations of curricula in support of the BME enterprise. The core principles of BME 2.0 education are (a) educate students bilingually, from day 1, in the languages of modern molecular biology and the analytical modeling of complex biological systems; (b) prepare every student to be a biomedical data scientist; (c) build a unique BME community for discovery and innovation via a vertically integrated and convergent learning environment spanning the university and hospital systems; (d) champion an educational culture of inclusive excellence; and (e) codify in the curriculum ongoing discoveries at the frontiers of the discipline, thus ensuring BME 2.0 as a launchpad for training the future leaders of the biotechnology marketplaces. We envision that the BME 2.0 education is the path for providing every student with the training to lead in this new era of engineering the future of medicine in the 21st century.

We need novel strategies to target the complexity of cancer and, particularly, of metastatic disease. As an example of this complexity, certain tissues are particularly hospitable environments for metastases, whereas others do not contain fertile microenvironments to support cancer cell growth. Continuing evidence that the extracellular matrix (ECM) of tissues is one of a host of factors necessary to support cancer cell growth at both primary and secondary tissue sites is emerging. Research on cancer metastasis has largely been focused on the molecular adaptations of tumor cells in various cytokine and growth factor environments on 2-dimensional tissue culture polystyrene plates. Intravital imaging, conversely, has transformed our ability to watch, in real time, tumor cell invasion, intravasation, extravasation, and growth. Because the interstitial ECM that supports all cells in the tumor microenvironment changes over time scales outside the possible window of typical intravital imaging, bioengineers are continuously developing both simple and sophisticated in vitro controlled environments to study tumor (and other) cell interactions with this matrix. In this perspective, we focus on the cellular unit responsible for upholding the pathologic homeostasis of tumor-bearing organs, cancer-associated fibroblasts (CAFs), and their self-generated ECM. The latter, together with tumoral and other cell secreted factors, constitute the "tumor matrisome". We share the challenges and opportunities for modeling this dynamic CAF/ECM unit, the tools and techniques available, and how the tumor matrisome is remodeled (e.g., via ECM proteases). We posit that increasing information on tumor matrisome dynamics may lead the field to alternative strategies for personalized medicine outside genomics.