Bioengineering & Translational Medicine最新文献

Low back pain is a global health challenge, imposing substantial socioeconomic burdens. Intervertebral disc degeneration (IVDD) is a leading cause of low back pain and can lead to further spinal complications. Current treatments for IVDD are limited to conservative measures and surgery, lacking curative options. Advances in biomaterials science and regenerative medicine have introduced bioactive hydrogels as promising treatments for IVDD. This review summarizes the physiology of the intervertebral disc, the pathophysiology of IVDD, existing diagnostic methods, and current treatment strategies. Importantly, this review examines recent advances in hydrogel treatments for IVDD, emphasizing the biological and material properties of various hydrogels. It compares the advantages and limitations of natural and synthetic hydrogels, outlining the classification of hydrogel delivery substances. Lastly, it identifies current challenges and suggests future research directions to optimize the application of bioactive materials in IVDD treatment.

There is a clinical need for an effective nerve guidance conduit to treat peripheral nerve injuries. Many studies have explored different materials and active cues to guide neural regeneration, with some success. However, none have demonstrated a comparable or better functional recovery than the clinical standard autograft. Autografts are often insufficient for reconstruction of an injury to long nerves such as the sciatic or brachial plexus. Synthetic nerve guidance conduits (NGCs) have been investigated for these injuries to guide axonal regeneration and lead to functional recovery. We have designed a biologics-free hydrogel-based multi-channel conduit with defined microscale features to guide axonal outgrowth. To investigate extraneural vascular infiltration and its effects on functional recovery, we also designed a multi-microchannel conduit with defined regularly spaced micropores, orthogonal to the axon guidance channels. Using our custom-built Rapid Projection, Image-guided, Dynamic (RaPID) bioprinting system, we were able to fabricate each hydrogel conduit within minutes from a milliliter-volume prepolymer vat. With our state-of-the-art printing platform, we have achieved NGCs with a consistent channel wall width of 10 μm. We implanted the NGCs for 17 weeks in a murine sciatic nerve transection injury model. We assessed the functional recovery by dynamic gait analysis throughout the recovery period and by compound muscle action potential (CMAP) electrophysiology before NGC harvesting. Both the non-porous and micro-porous conduit groups led to functional nerve regeneration on par with the autograft group. Further, both conduit groups resulted in restoration of bulk motor function to pre-injury performance.

Zhang B, Zhao Y, Guo K, et al. Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease. Bioeng Transl Med. 2023;8(3):e10459.

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Pain is a key symptom associated with rheumatoid arthritis (RA) and can persist even in the context of overall disease control by standard-of-care disease modifying anti-rheumatic drugs (DMARDs). Analgesic agents and corticosteroids are often used to supplement DMARDs for pain relief but lack disease modifying properties, and their sustained use carries adverse risks. In this work, we characterized the progression of pain sensitivity in the SKG mouse model of RA and evaluated the potential therapeutic interventions. Male and female SKG mice, after systemic mannan injection, developed a mechanical pain phenotype and joint swelling, with a strong inverse correlation between clinical arthritis scores and pain thresholds. To test potential interventions for pain alleviation, we evaluated all-trans retinoic acid (ATRA)-loaded poly(lactic-co-glycolic acid) microparticles (ATRA-PLGA MP) administered via intra-articular injection, which we have previously demonstrated to be disease-modifying. The pain and inflammation patterns assessed by the von Frey test and clinical scoring showed ATRA-PLGA MP monotherapy reduced inflammation and alleviated mechanical allodynia in arthritic SKG mice, an effect that was amplified by combination treatments with standard-of-care agents. In early-stage arthritis, co-administration with cytotoxic T-lymphocyte-associated protein (CTLA)-4-Ig, clinically known as abatacept, delayed disease progression and sustained the reduction of mechanical allodynia. In established arthritis, sequential treatment with the corticosteroid dexamethasone (Dex) reduced cumulative disease burden and reduced mechanical allodynia. These findings highlight the potential of combining ATRA-PLGA MP with standard-of-care treatments as a potential strategy to enhance the efficacy and durability of disease modification and pain alleviation for arthritis management.

An abdominal aortic aneurysm (AAA) is a life-threatening vascular condition characterized by the dilation of the abdominal aorta, with ferroptosis playing a significant role in its pathogenesis. This study investigates the therapeutic potential of engineering biomimetic nanovesicles to deliver phosphatidylethanolamine-binding protein 1 (PEBP1) mRNA for inhibiting ferroptosis in vascular smooth muscle cells (VSMCs) and preventing AAA progression. Differential gene expression analysis of the AAA transcriptomic dataset GSE57691 identified 243 differentially expressed genes (DEGs), intersecting with 12 ferroptosis-related genes. Single-cell analysis of dataset GSE237230 highlighted PEBP1 as a key gene in VSMCs. Overexpression of PEBP1 in VSMCs enhanced proliferation, reduced reactive oxygen species (ROS) and iron levels, and inhibited apoptosis and ferroptosis via the NRF2/GPX4 axis. The engineered biomimetic nanovesicles demonstrated significant uptake by VSMCs and effective delivery of PEBP1 mRNA. In vivo studies confirmed that these nanovesicles substantially inhibited AAA progression in mice. This study presents a novel bioengineering approach for AAA treatment by targeting ferroptosis through PEBP1 mRNA delivery, offering a promising molecular strategy for the prevention and management of AAA.