Programmable Photoswitchable Microcapsules Enable Precise and Tailored Drug Delivery from Microfluidics.

The development of precision personalized medicine poses a significant need for the next generation of advanced diagnostic and therapeutic technologies, and one of the key challenges is the development of highly time-, space-, and dose-controllable drug delivery systems that respond to the complex physiopathology of patient populations. In response to this challenge, an increasing number of stimuli-responsive smart materials are integrated into biomaterial systems for precise targeted drug delivery. Among them, responsive microcapsules prepared by droplet microfluidics have received much attention. In this study, we present a UV-visible light cycling mediated photoswitchable microcapsule (PMC) with dynamic permeability-switching capability for precise and tailored drug release. The PMCs were fabricated using a programmable pulsed aerodynamic printing (PPAP) technique, encapsulating an aqueous core containing magnetic nanoparticles and the drug doxorubicin (DOX) within a poly(lactic-co-glycolic acid) (PLGA) composite shell modified by PEG-b-PSPA. Selective irradiation of PMCs with ultraviolet (UV) or visible light (Vis) allows for high-precision time-, space-, and dose-controlled release of the therapeutic agent. An experimentally validated theoretical model was developed to describe the drug release pattern, holding promise for future customized programmable drug release applications. The therapeutic efficacy and value of patternable cancer cell treatment activated by UV radiation is demonstrated by our experimental results. After in vitro transcatheter arterial chemoembolization (TACE), PMCs can be removed by external magnetic fields to mitigate potential side effects. Our findings demonstrate that PMCs have the potential to integrate embolization, on-demand drug delivery, magnetic actuation, and imaging properties, highlighting their immense potential for tailored drug delivery and embolic therapy.

Oxygen-releasing biomaterials for regenerative medicine.

Oxygen is critical to the survival, function and fate of mammalian cells. Oxygen tension controls cellular behavior through metabolic programming, which in turn controls tissue regeneration. A variety of biomaterials with oxygen-releasing capabilities have been developed to provide oxygen supply to ensure cell survival and differentiation for therapeutic efficacy, and to prevent hypoxia-induced tissue damage and cell death. However, controlling the oxygen release with spatial and temporal accuracy is still technically challenging. In this review, we provide a comprehensive overview of organic and inorganic materials available as oxygen sources, including hemoglobin-based oxygen carriers (HBOCs), perfluorocarbons (PFCs), photosynthetic organisms, solid and liquid peroxides, and some of the latest materials such as metal-organic frameworks (MOFs). Additionally, we introduce the corresponding carrier materials and the oxygen production methods and present state-of-the-art applications and breakthroughs of oxygen-releasing materials. Furthermore, we discuss the current challenges and the future perspectives in the field. After reviewing the recent progress and the future perspectives of oxygen-releasing materials, we predict that smart material systems that combine precise detection of oxygenation and adaptive control of oxygen delivery will be the future trend for oxygen-releasing materials in regenerative medicine.

A photo-responsive membrane for tailored drug delivery with spatially and temporally controlled release.

Accurate delivery of therapeutics to tumor regions and effective sparing of normal tissue structures are important principles for the treatment of widespread metastases or malignant lesions in close proximity to vital organs. However, the currently available drug delivery techniques do not support precise drug release within the identified disease margins. We propose a tailored drug delivery strategy that utilizes a photo-responsive material in combination with tumor margin imaging for automated and tailored release of therapeutics. As a proof of concept, a poly(ethylene oxide)-b-PSPA (PEO-b-PSPA) diblock copolymer is synthesized by spiropyran (SP) polymerization. A photo-responsive membrane (PRM) is formed and irradiated with light sources of different wavelengths. Switching irradiation between ultraviolet light (UV) and green light (Vis) controls the permeability of the PRM in coincidence with the programmed irradiation patterns. The dynamic process of photo-switchable drug permeation through the PRM is modeled and compared with the experimental results. The strategy of tailored drug release is verified using both regular geometric shapes and metastatic cancer images. The therapeutic effect of this tailored drug release strategy is demonstrated in vitro in human breast cancer cells. Our pilot study implies the technical potential of using photo-responsive carriers for image-guided chemotherapy with precisely controlled drug release patterns.

Multimodal 3D Printing of Phantoms to Simulate Biological Tissue.

Biomedical optical imaging is playing an important role in diagnosis and treatment of various diseases. However, the accuracy and the reproducibility of an optical imaging device are greatly affected by the performance characteristics of its components, the test environment, and the operations. Therefore, it is necessary to calibrate these devices by traceable phantom standards. However, most of the currently available phantoms are homogeneous phantoms that cannot simulate multimodal and dynamic characteristics of biological tissue. Here, we show the fabrication of heterogeneous tissue-simulating phantoms using a production line integrating a spin coating module, a polyjet module, a fused deposition modeling (FDM) module, and an automatic control framework. The structural information and the optical parameters of a "digital optical phantom" are defined in a prototype file, imported to the production line, and fabricated layer-by-layer with sequential switch between different printing modalities. Technical capability of such a production line is exemplified by the automatic printing of skin-simulating phantoms that comprise the epidermis, dermis, subcutaneous tissue, and an embedded tumor.

[NK-T cell activator (α-GalCer) accelerates immune and hematological reconstitution after murine allo-bone marrow transplantation].

Immune reconstitution is crucially relevant for patients receiving hematopoietic stem cell transplantation (HSCT). This study was purposed to investigate the ability of α-GalCer (α-galactosylceramide), a well-known activator of natural killer T cells (NK-T), to enhance immune and hematological reconstitution. Lethally irradiated BALB/c mice were transplanted with allogeneic C57BL/6 bone marrow cells and splenocytes. α-GalCer was administered immediately after HSCT. After transplantation, the weight, activity, hairs, diarrhea and survival time of mice were observed daily; the blood routine test was performed once weekly; the donor chimeras, amount of mononuclear cells in spleen (MNC) and relative levels of CD3(+), CD4(+), CD8(+), B220(+), CD11c(+), CD40(+), CD86(+) and CD80(+) cells were detected by FACS on day 2, 7, 14, 27, 70 after transplantation. The results indicated that the MNC counts and relative levels of CD3(+) and CD4(+) in group treated with α-GalCer on day 2 after transplantation were higher than those in control group; at the same time, the detected donor chimeras were complete recipient type chimeras, then gradually transformed into donor type, on day 7 - 14 donor chimeras in α-GalCer group were enhanced significantly as compared with control group, on day 27 the chimeras in two groups were complete donor type chimeras thereafter to day 70, the MNC count and relative levels of CD3(+), CD4(+), CD8(+), B220(+), CD40(+), CD86(+) cells in α-GalCer group were obviously higher than those in control group, at the same time, the hematopoietic reconstitution in α-GalCer group was accelerated as compared with control group. It is concluded that the α-GalCer administration after allogeneic bone marrow transplantations accelerates immune and hematological reconstitution.