An Adaptable Drug Delivery System Facilitates Peripheral Nerve Repair by Remodeling the Microenvironment.

The multifaceted process of nerve regeneration following damage remains a significant clinical issue, due to the lack of a favorable regenerative microenvironment and insufficient endogenous biochemical signaling. However, the current nerve grafts have limitations in functionality, as they require a greater capacity to effectively regulate the intricate microenvironment associated with nerve regeneration. In this regard, we proposed the construction of a functional artificial scaffold based on a "two-pronged" approach. The whole system was developed by encapsulating Tazarotene within nanomicelles formed through self-assembly of reactive oxygen species (ROS)-responsive amphiphilic triblock copolymer, all of which were further loaded into a thermosensitive injectable hydrogel. Notably, the hydrogel exhibits obvious temperature sensitivity at a concentration of 6 wt %, and the nanoparticles possess concentration-dependent H2O2-response capability with a controlled release profile in 48 h. The combined strategy promoted the repair of injured peripheral nerves, attributed to the dual role of the materials, which mainly involved providing structural support, modulating the immune microenvironment, and enhancing angiogenesis. Overall, this study opens up intriguing prospects in tissue engineering.

A Novel Redox-Sensitive Drug Delivery System Based on Trimethyl-Locked Polycarbonate.

Stimuli-responsive polymer nanocarriers, capable of exploiting subtle changes in the tumor microenvironment for controlled drug release, have gained significant attention in cancer therapy. Notably, NAD(P)H: quinone oxidoreductase 1 (NQO1), found to be upregulated in various solid tumors, represents a promising therapeutic target due to its effective capability to enzymatically reduce trimethyl-locked (TML) benzoquinone structures in a physiological condition. In this study, a novel redox-sensitive carbonate monomer, MTC, was synthesized, and its amphiphilic block copolymers were prepared through ring-opening polymerization. By successfully self-assembling poly(ethylene glycol)-b-PMTC micelles, the model drug doxorubicin (DOX) was encapsulated with high efficiency. The micelles exhibited redox-responsive behavior, leading to rapid drug release. In vitro assessments confirmed their excellent biocompatibility and hemocompatibility. Furthermore, the inhibition of the NQO1 enzyme reduced drug release in NQO1-overexpressed cells but not in control cells, resulting in decreased cytotoxicity in the presence of NQO1 enzyme inhibitors. Overall, this study showcases the potential of MTC-based polycarbonate micelles to achieve targeted and specific drug release in the NQO1 enzyme-mediated tumor microenvironment. Therefore, the self-assembly of MTC-based polymers into nanomicelles holds immense promise as intelligent nanocarriers in drug delivery applications.

A Novel NQO1 Enzyme-Responsive Polyurethane Nanocarrier for Redox-Triggered Intracellular Drug Release.

The design of nano-drug delivery vehicles responsive to tumor microenvironment stimuli has become a crucial aspect in developing cancer therapy in recent years. Among them, the enzyme-responsive nano-drug delivery system is particularly effective, as it utilizes tumor-specific and highly expressed enzymes as precise targets, leading to increased drug release at the target sites, reduced nonspecific release, and improved efficacy while minimizing toxic side effects on normal tissues. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an important reductase associated with cancer and is overexpressed in some cancer cells, particularly in lung and breast cancer. Thus, the design of nanocarriers with high selectivity and responsiveness to NQO1 is of great significance for tumor diagnosis and treatment. It has been reported that under physiological conditions, NQO1 can specifically reduce the trimethyl-locked benzoquinone structure through a two-electron reduction, resulting in rapid lactonization via an enzymatic reaction. Based on this, a novel reduction-sensitive polyurethane (PEG-PTU-PEG) block copolymer was designed and synthesized by copolymerizing diisocyanate, a reduction-sensitive monomer (TMBQ), and poly(ethylene glycol). The successful synthesis of monomers and polymers was verified by nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC). Then, the PEG-PTU-PEG micelles were successfully prepared by self-assembly, and their reductive dissociation behavior in the presence of Na2S2O4 was verified by dynamic light scattering (DLS), 1H NMR, and GPC. Next, the model drug doxorubicin (DOX) was encapsulated into the hydrophobic core of this polyurethane micelles by microemulsion method. It was observed that the drug-loaded micelles could also achieve a redox response and rapidly release the encapsulated substances. In vitro cell experiments demonstrated that PEG-PTU-PEG micelles had good biocompatibility and a low hemolysis rate (<5%). Furthermore, in the presence of an NQO1 enzyme inhibitor (dicoumarol), lower drug release from micelles was observed in A549 and 4T1 cells by both fluorescence microscopy and flow cytometry assays, but not in NIH-3T3 control cells. Predictably, DOX-loaded micelles also showed lower cytotoxicity in 4T1 cells in the presence of NQO1 enzyme inhibitors. These results indicate that drug-loaded polyurethane micelles could accomplish specific drug release in the reducing environment in the presence of NQO1 enzymes. Therefore, this study provides a new option for the construction of polyurethane nanocarriers for precise targeting and reductive release, which could benefit the intracellular drug-specific release and precision therapy of tumors.

Novel Donor-Acceptor Conjugated Polymer-Based Nanomicelles for Photothermal Therapy in the NIR Window.

In this study, a novel donor-acceptor conjugated polymer PDPPDTP was designed and synthesized by D-A polymerization using 2,6-di(trimethyltin)-N-dithieno[3,2-b:20,30-d]pyrrole as the electron-donating (D) unit and 3,6-bis(5-bromothiophen-2-yl)-2,5-dihexadecylpyrrolo[3,4-c]pyrrole-1,4-dione as the electron-accepting (A) unit. The prepared polymer has strong absorption in the near-infrared (NIR) range of 700-900 nm. Moreover, it shows excellent photothermal performance under irradiation at 808 nm. Next, the biodegradable amphiphilic polymer polyethylene glycol-polycaprolactone was used to encapsulate the new conjugated polymer into nanomicelles by the microemulsion method. The obtained PDPPDTP-loaded micelles exhibited a regular spherical structure, and their hydrodynamic diameter was about 78 nm, characterized by transmission electron microscopy and dynamic light scattering. Notably, the micelles exhibited good stability, and the encapsulation efficiency of the conjugated polymer in the micelles was ∼80%. In vitro cell experiments demonstrated that the nanomicelles not only showed good biocompatibility and low toxicity but also could effectively inhibit the proliferation of breast cancer cells 4T1 under the NIR light irradiation of 808 nm. Furthermore, in vivo studies of photothermal therapy (PTT) efficacy showed that the PDPPDTP-loaded micelles exhibited a remarkable tumor growth inhibition in a syngeneic murine tumor model, indicating that the nanomicelles loaded with this novel conjugated polymer could be further explored as a new type of theranostic agent and applied in the PTT of tumors.

Dextran-Benzoporphyrin Derivative (BPD) Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Micelles for T2-Weighted Magnetic Resonance Imaging and Photodynamic Therapy.

Photodynamic therapy (PDT) has attracted extensive attention in recent years as a noninvasive and locally targeted cancer treatment approach. Nanoparticles have been used to improve the solubility and pharmacokinetics of the photosensitizers required for PDT; however, nanoparticles also suffer from many shortcomings including uncontrolled drug release and low tumor accumulation. Herein, we describe a novel biodegradable nanoplatform for the delivery of the clinically used PDT photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA) to tumors. Specifically, the hydrophobic photosensitizer BPD was covalently conjugated to the amine groups of a dextran-b-oligo (amidoamine) (dOA) dendron copolymer, forming amphiphilic dextran-BPD conjugates that can self-assemble into nanometer-sized micelles in water. To impart additional imaging capabilities to these micelles, superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated within the hydrophobic core to serve as a magnetic resonance imaging (MRI) contrast agent. The use of a photosensitizer as a hydrophobic building block enabled facile and reproducible synthesis and high drug loading capacity (∼30%, w/w). Furthermore, covalent conjugation of BPD to dextran prevents the premature release of drug during systemic circulation. In vivo studies show that the intravenous administration of dextran-BPD coated SPION nanoparticles results in significant MR contrast enhancement within tumors 24 h postinjection and PDT led to a significant reduction in the tumor growth rate.

Site-Specific Labeling of Cyanine and Porphyrin Dye-Stabilized Nanoemulsions with Affibodies for Cellular Targeting.

Recently, it has been shown that amphiphilic dyes such as Indocyanine Green (ICG) and Protoporphyrin IX (PpIX) can solubilize hydrophobic colloids and/or drugs by driving the formation of stable nanoemulsions. These nanoemulsions are unique in that they can be composed entirely of functional and clinically used materials; however, they lack bio-orthogonal chemical handles for the facile attachment of targeting ligands. The ability to target nanoparticles is desirable because it can lead to improved specificity and reduced side effects. Here, we describe variants of ICG and PpIX with azide handles that can be readily incorporated into dye-stabilized nanoemulsions and facilitate the attachment of targeting ligands via click-chemistry in a simple, scalable, and reproducible reaction. As a model system, an anti-Her2 affibody was site-specifically attached to both ICG and PpIX-stabilized nanoemulsions with encapsulated superparamagnetic iron oxide nanoparticles.

Protoporphyrin IX (PpIX)-Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters for Magnetic Resonance Imaging and Photodynamic Therapy.

The ability to produce nanotherapeutics at large-scale with high drug loading efficiency, high drug loading capacity, high stability, and high potency is critical for clinical translation. However, many nanoparticle-based therapeutics under investigation suffer from complicated synthesis, poor reproducibility, low stability, and high cost. In this work, a simple method for preparing multifunctional nanoparticles is utilized that act as both a contrast agent for magnetic resonance imaging and a photosensitizer for photodynamic therapy for the treatment of cancer. In particular, the photosensitizer protoporphyrin IX (PpIX) is used to solubilize small nanoclusters of superparamagnetic iron oxide nanoparticles (SPIONs) without the use of any additional carrier materials. These nanoclusters are characterized with a high PpIX loading efficiency; a high loading capacity, stable behavior; high potency; and a synthetic approach that is amenable to large-scale production. In vivo studies of photodynamic therapy (PDT) efficacy show that the PpIX-coated SPION nanoclusters lead to a significant reduction in the growth rate of tumors in a syngeneic murine tumor model compared to both free PpIX and PpIX-loaded poly(ethylene glycol)-polycaprolactone micelles, even when injected at 1/8th the dose. These results suggest that the nanoclusters developed in this work can be a promising nanotherapeutic for clinical translation.

Photoacoustic-Guided Surgery with Indocyanine Green-Coated Superparamagnetic Iron Oxide Nanoparticle Clusters.

A common cause of local tumor recurrence in brain tumor surgery results from incomplete surgical resection. Adjunctive technologies meant to facilitate gross total resection have had limited efficacy to date. Contrast agents used to delineate tumors preoperatively cannot be easily or accurately used in the real-time operative setting. Although multimodal imaging contrast agents are developed to help the surgeon discern tumor from normal tissue in the operating room, these contrast agents are not readily translatable. This study has developed a novel contrast agent comprised solely of two Food and Drug Administration approved components, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) nanoparticles-with no additional amphiphiles or carrier materials, to enable preoperative detection by magnetic resonance (MR) imaging and intraoperative photoacoustic (PA) imaging. The encapsulation efficiency of both ICG and SPIO within the formulated clusters is ≈100%, and the total ICG payload is 20-30% of the total weight (ICG + SPIO). The ICG-SPIO clusters are stable in physiologic conditions; can be taken up within tumors by enhanced permeability and retention; and are detectable by MR. In a preclinical surgical resection model in mice, following injection of ICG-SPIO clusters, animals undergoing PA-guided surgery demonstrate increased progression-free survival compared to animals undergoing microscopic surgery.

Improved Photodynamic Therapy Efficacy of Protoporphyrin IX-Loaded Polymeric Micelles Using Erlotinib Pretreatment.

Photodynamic therapy (PDT) has attracted widespread attention in recent years as a noninvasive and highly selective approach for cancer treatment. We have previously reported a significant increase in the 90-day complete response rate when tumor-bearing mice are treated with the epidermal growth factor receptor (EGFR) inhibitor erlotinib prior to PDT with the photosensitizer benzoporphyrin-derivative monoacid ring A (BPD-MA) compared to treatment with PDT alone. To further explore this strategy for anticancer therapy and clinical practice, we tested whether pretreatment with erlotinib also exhibited a synergistic therapeutic effect with a nanocarrier containing the clinically relevant photosensitizer protoporphyrin IX (PpIX). The PpIX was encapsulated within biodegradable polymeric micelles formed from the amphiphilic block copolymer poly(ethylene glycol)-polycaprolactone (PEG-PCL). The obtained micelles were characterized systematically in vitro. Further, an in vitro cytotoxicity study showed that PDT with PpIX loaded micelles did exhibit a synergistic effect when combined with erlotinib pretreatment. Considering the distinct advantages of polymeric nanocarriers in vivo, this study offers a promising new approach for the improved treatment of localized tumors. The strategy developed here has the potential to be extended to other photosensitizers currently used in the clinic for photodynamic therapy.

Turning Ineffective Transplatin into a Highly Potent Anticancer Drug via a Prodrug Strategy for Drug Delivery and Inhibiting Cisplatin Drug Resistance.

Clinically ineffective transplatin is highly potent against cancer cells when transformed into a transplatin(IV) prodrug nanoparticle. Herein, a hydrophobic transplatin(IV) was synthesized by H2O2-oxidization of transplatin and attachment of two hydrophobic aliphatic chains. Transplatin(IV) was subsequently encapsulated by a biodegradable amphiphilic copolymer, MPEG-PLA, forming a well-defined spherical micelles (M(TransPt)). Transplatin(IV) was protected efficiently and could be released under a simulated cancerous intracellular condition. Compared to the cisplatin and transplatin, M(TransPt) showed the highest Pt uptake and a clathrin-dependent endocytosis pathway. Most importantly, M(TransPt) displayed a nanomolar IC50 on A2780 cells and a great potency on cisplatin resistant A2780DDP cell line. Overall, this nanoplatform for delivering trans-geometry platinum(IV) drug exhibits excellent characteristics for enhancing efficacy and overcoming cisplatin drug resistance, and holds a strong promise for clinical use in the near future.

Self-Targeted Polysaccharide Prodrug Suppresses Orthotopic Hepatoma.

Self-targetability is an emerging targeting strategy for polymer nanocarriers with facile preparation and high targeting efficiency. An acid-sensitive dextran-doxorubicin prodrug (Dex-g-DOX) has been synthesized and used as a self-targeted drug delivery system for the treatment of orthotopic hepatoma. The polysaccharide prodrug exhibits ultraselective accumulation in cancerous liver tissue, acid-sensitive DOX release within cells, and high antitumor efficacy in vitro and in vivo. Therefore, Dex-g-DOX demonstrates great potential for chemotherapy of orthotopic hepatoma.

Sonodynamic-chemotherapy synergy with chlorin e6-based carrier-free nanoparticles for non-small cell lung cancer.

Sonodynamic therapy (SDT), an emerging cancer treatment with significant potential, offers the advantages of non-invasiveness and deep tissue penetrability. The method involves activating sonosensitizers with ultrasound to generate reactive oxygen species (ROS) capable of eradicating cancer cells, addressing the challenge faced by photodynamic therapy (PDT) where conventional light sources struggle to penetrate deep tissues, impacting treatment efficacy. This study addresses prevalent challenges in numerous nanodiagnostic and therapeutic agents, such as intricate synthesis, poor repeatability, low stability, and high cost, by introducing a streamlined one-step assembly method for nanoparticle preparation. Specifically, the sonosensitizer Chlorin e6 (Ce6) and the chemotherapy drug erlotinib are effortlessly combined and self-assembled under sonication, yielding carrier-free nanoparticles (EC-NPs) for non-small cell lung cancer (NSCLC) treatment. The resulting EC-NPs exhibit optimal drug loading capacity, a simplified preparation process, and robust stability both in vitro and in vivo, owing to their carrier-free characteristics. Under the synergistic treatment of sonodynamic therapy and chemotherapy, EC-NPs induce an excess of reactive oxygen in tumor tissue, prompting apoptosis of cancer cells and reducing their proliferative capacity. Both in vitro and in vivo experiments demonstrate superior therapeutic effects of EC-NPs under ultrasound conditions compared to free Ce6. In summary, our research findings highlight that the innovatively designed carrier-free sonosensitizer EC-NPs present a therapeutic option with commendable efficacy and minimal side effects.

Pleiotropic effects of nitric oxide sustained-release system for peripheral nerve repair.

The regenerative microenvironment after peripheral nerve injury is imbalanced and difficult to rebalance, which is mainly affected by inflammation, oxidative stress, and inadequate blood supply. The difficulty in remodeling the nerve regeneration microenvironment is the main reason for slow nerve regeneration. Traditional drug treatments have certain limitations, such as difficulty in penetrating the blood-nerve barrier and lack of pleiotropic effects. Therefore, there is an urgent need to build multifunctional nerve grafts that can effectively regulate the regenerative microenvironment and promote nerve regeneration. Nitric oxide (NO), a highly effective gas transmitter with diatomic radicals, is an important regulator of axonal growth and migration, synaptic plasticity, proliferation of neural precursor cells, and neuronal survival. Moreover, NO provides potential anti-inflammation, anti-oxidation, and blood vessel promotion applications. However, excess NO may cause cell death and neuroinflammatory cell damage. The prerequisite for NO treatment of peripheral nerve injury is that it is gradually released over time. In this study, we constructed an injectable NO slow-release system with two main components, including macromolecular NO donor nanoparticles (mPEG-P(MSNO-EG) nanoparticles, NO-NPs) and a carrier for the nanoparticles, mPEG-PA-PP injectable temperature-sensitive hydrogel. Due to the multiple physiological regulation of NO and better physiological barrier penetration, the conduit effectively regulates the inflammatory response and oxidative stress of damaged peripheral nerves, promotes nerve vascularization, and nerve regeneration and docking, accelerating the nerve regeneration process. STATEMENT OF SIGNIFICANCE: The slow regeneration speed of peripheral nerves is mainly due to the destruction of the regeneration microenvironment. Neural conduits with drug delivery capabilities have the potential to improve the microenvironment of nerve regeneration. However, traditional drugs are hindered by the blood nerve barrier and cannot effectively target the injured area. NO, an endogenous gas signaling molecule, can freely cross the blood nerve barrier and act on target cells. However, excessive NO can lead to cell apoptosis. In this study, a NO sustained-release system was constructed to regulate the microenvironment of nerve regeneration through various pathways and promote nerve regeneration.

A reduction-sensitive carrier system using mesoporous silica nanospheres with biodegradable polyester as caps.

Mesoporous silica nanoparticles (MSN)-polymer hybrid combined with the aliphatic biodegradable polyester caps on the surface were first developed in order to manipulate the smart intracellular release of anticancer drugs. First, poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) was successfully grafted on the surface of MSN via disulfide bonds which could cleave under a reduction environment in tumor cells. The anticancer drug doxorubicin (DOX) was encapsulated into the particle pores. The in vitro drug release profile showed that DOX release was significantly restricted by the polymer caps at pH 7.4, while it was greatly accelerated upon the addition of GSH. Cytotoxicity evaluation showed good biocompatibility with the hybrid particles. Fast endocytosis and intracellular DOX release were observed by confocal laser scanning microscopy (CLSM). The DOX-loaded particles exhibited comparable antitumor activity with free DOX towards HeLa cells and showed in a time-dependent manner. This work developed an extensive method of utilizing aliphatic biodegradable polyesters as polymer caps for MSN to control drug delivery. The paper might offer a potential option for cancer therapy.

Nanoparticle-Mediated Delivery of Satraplatin to Overcome Cisplatin Drug Resistance.

Drug resistance and cancer metastasis are the major obstacles for widely used platinum-based chemotherapy. It is acknowledgement that the decreasing intracellular accumulation of anticancer drugs and increasing sulfur-binding detoxification are two major mechanisms related to drug resistance. Herein, we developed a practical and straightforward method for formulating the clinically used anticancer drug satraplatin (JM-216) with D-α-tocopheryl polyethylene glycol succinate (TPGS)-based polymers to create satraplatin-loaded nanoparticles (SatPt-NPs). The experimental results demonstrate that SatPt-NPs exhibited comparable efficacy to A2780 in treating the A2780 cisplatin-resistant ovarian cancer cell line (A2780DDP), indicating their significant potential in overcoming drug resistance. Additionally, buthionine sulfoximine (BSO) is capable of depleting intracellular glutathione (GSH), resulting in reduced detoxification. After BSO treatment, the IC50 value of SatPt-NPs changed from 0.178 to 0.133 µM, which remained relatively unchanged compared to cisplatin. This suggests that SatPt-NPs can overcome drug resistance by evading GSH detoxification. Therefore, SatPt-NPs have the ability to inhibit drug resistance in tumor cells and hold tremendous potential in cancer treatment.

The effect of silicon groups on the physicochemical property and bioactivity of L-phenylalanine derived poly(amide-imide).

Poly(amide-imide) (PAI), serving as a synthetic polymer, has been widely used in industry for excellent mechanical properties, chemical resistance and high thermal stability. However, lack of suitable cell niche and biological activity limited the further application of PAI in biomedical engineering. Herein, silicon modified L-phenylalanine derived poly(amide-imide) (PAIS) was synthesized by introducing silica to L-phenylalanine derived PAI to improve physicochemical and biological performances. The influence of silicon amount on physicochemical, immune, and angiogenic performances of PAIS were systemically studied. The results show that PAIS exerts excellent hydrophilic, mechanical, biological activity. PAIS shows no effects on the number of macrophages, but can regulate macrophage polarization and angiogenesis in a dose-dependent manner. This study advanced our understanding of silicon modification in PAI can modulate cell responses via initiating silicon concentration regulation. The acquired knowledge will provide a new strategy to design and optimize biomedical PAI in the future.

An injectable and adaptable hydrogen sulfide delivery system for modulating neuroregenerative microenvironment.

Peripheral nerve regeneration is a complex physiological process. Single-function nerve scaffolds often struggle to quickly adapt to the imbalanced regenerative microenvironment, leading to slow nerve regeneration and limited functional recovery. In this study, we demonstrate a "pleiotropic gas transmitter" strategy based on endogenous reactive oxygen species (ROS), which trigger the on-demand H2S release at the defect area for transected peripheral nerve injury (PNI) repair through concurrent neuroregeneration and neuroprotection processing. This H2S delivery system consists of an H2S donor (peroxyTCM) encapsulated in a ROS-responsive polymer (mPEG-PMet) and loaded into a temperature-sensitive poly (amino acid) hydrogel (mPEG-PA-PP). This multi-effect combination strategy greatly promotes the regeneration of PNI, attributed to the physiological effects of H2S. These effects include the inhibition of inflammation and oxidative stress, protection of nerve cells, promotion of angiogenesis, and the restoration of normal mitochondrial function. The adaptive release of pleiotropic messengers to modulate the tissue regeneration microenvironment offers promising peripheral nerve repair and tissue engineering opportunities.

Recent progress of nanomedicine in secreted phospholipase A2 as a potential therapeutic target.

Overexpressed secretory phospholipase A2 (sPLA2) is found in many inflammatory diseases and various types of cancer. sPLA2 can catalyze the hydrolysis of phospholipid sn-2 ester bonds to lysophosphatidylcholine and free fatty acids, and its catalytic substrate and downstream products mediate a series of cascade reactions and inflammatory responses. Furthermore, different subtypes of sPLA2 can participate in different physiological processes by driving unique lipid pathways. Recently, many diseases have not been treated by appropriate chemotherapy methods due to low bioavailability and severe side effects of clinically available small-molecule drugs. Therefore, they have great development prospects of revealing the therapeutic mechanism of sPLA2 and use sPLA2 as a potential therapeutic target for designing and exploring new drugs and their delivery systems. Notably, the emergence of nanomedicines in recent years provides a practical and innovative means for overcoming the challenges associated with chemotherapy. With these considerations in mind, this paper systematically reviews recent studies on nanomedicines targeting sPLA2 overexpression in various diseases during the past few years.

3D Printed Personalized Nerve Guide Conduits for Precision Repair of Peripheral Nerve Defects.

The treatment of peripheral nerve defects has always been one of the most challenging clinical practices in neurosurgery. Currently, nerve autograft is the preferred treatment modality for peripheral nerve defects, while the therapy is constantly plagued by the limited donor, loss of donor function, formation of neuroma, nerve distortion or dislocation, and nerve diameter mismatch. To address these clinical issues, the emerged nerve guide conduits (NGCs) are expected to offer effective platforms to repair peripheral nerve defects, especially those with large or complex topological structures. Up to now, numerous technologies are developed for preparing diverse NGCs, such as solvent casting, gas foaming, phase separation, freeze-drying, melt molding, electrospinning, and three-dimensional (3D) printing. 3D printing shows great potential and advantages because it can quickly and accurately manufacture the required NGCs from various natural and synthetic materials. This review introduces the application of personalized 3D printed NGCs for the precision repair of peripheral nerve defects and predicts their future directions.

Rapid, site-specific labeling of "off-the-shelf" and native serum autoantibodies with T cell-redirecting domains.

Extensive antibody engineering and cloning is typically required to generate new bispecific antibodies. Made-to-order genes, advanced expression systems, and high-efficiency cloning can simplify and accelerate this process, but it still can take months before a functional product is realized. We developed a simple method to site-specifically and covalently attach a T cell-redirecting domain to any off-the-shelf, human immunoglobulin G (IgG) or native IgG isolated from serum. No antibody engineering, cloning, or knowledge of the antibody sequence is required. Bispecific antibodies are generated in just hours. By labeling antibodies isolated from tumor-bearing mice, including two syngeneic models, we generated T cell-redirecting autoantibodies (TRAAbs) that act as an effective therapeutic. TRAAbs preferentially bind tumor tissue over healthy tissue, indicating a previously unexplored therapeutic window. The use of autoantibodies to direct the tumor targeting of bispecific antibodies represents a new paradigm in personalized medicine that eliminates the need to identify tumor biomarkers.