MedComm – Biomaterials and Applications最新文献

This study used polymer micropatches as a platform for sustained and targeted activation of neutrophils. The micropatches can promote the rapid conversion of neutrophils to the N1 type while also enhancing the activation of other immune cells in vivo. The activated neutrophils are recruited to the tumor site, where they exert effective antitumor effects.

Taeghwan Hyeon of the Institute for Basic Science (IBS) in Korea, Youngmee Jung of the Korea Institute of Science and Technology (KIST), and Byung-Soo Kim of Seoul National University, in collaboration with other researchers, recently devised a hybrid system involving ceria nanoparticles (Ce NPs) attached to mesenchymal stem cell nanovesicles to target the various pathogenic factors associated with rheumatoid arthritis (RA). This study demonstrates the efficacy of the therapy in treating and preventing RA through symptom relief and the induction of regulatory T (Treg) cells in a collagen-induced arthritis (CIA) mouse model. The findings were published in the prestigious journal, Nature Nanotechnology.¹

RA is characterized by inflammatory autoimmune responses that lead to the loss of immune tolerance, synovial inflammation, and tissue damage, ultimately causing systemic and persistent functional limitations.² The precise etiology of RA remains uncertain; however, it is established that the aforementioned factors can synergistically contribute to a self-perpetuating cycle that significantly influences the onset and progression of the disease. The standard initial approach to managing RA involves the administration of anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biologics, albeit these pharmacological interventions primarily target symptom alleviation. While this method may provide short-term relief, it is crucial to acknowledge the potential adverse effects that may arise from prolonged drug use. As such, the optimal approach to treating RA should prioritize the restoration of normal immune function and the prompt suppression of inflammatory reactions and associated symptoms.³

Numerous studies have demonstrated the effective modulation of innate immunity through the promotion of anti-inflammatory M2 macrophages. Nevertheless, RA represents a chronic autoimmune condition that requires a more holistic strategy to restore immune function within both the innate and adaptive immune responses. Failing to achieve this objective necessitates the continued administration of palliative drugs, underscoring the critical need for a multifaceted intervention system capable of targeting numerous pathogenic factors to ensure comprehensive treatment of RA.⁴

The Ce–mesenchymal stem cell nanovesicle (MSCNV) system is engineered to capitalize on the antioxidant properties of Ce NPs to neutralize reactive oxygen species (ROS), a pivotal pathogenic factor in RA, and to induce a phenotypic shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages. Simultaneously, MSCNVs within the hybrid system protect chondrocytes and deliver immunomodulatory cytokines, fostering a tolerogenic phenotype in dendritic cells (DCs) and the subsequent induction of Treg cells. This dual

In a recent paper published in Nature Communications, Zhong et al.¹ described a wireless battery-free ocular modulation patch. This patch could be utilized in posterior scleral reinforcement (PSR) surgery, to correct high myopia by shortening the axial length (AXL) and reinforce the sclera to prevent myopia recurrence.

Myopia is a state of refraction in which parallel rays of light coming from infinity are brought to focus in front of the retina. The mechanism of myopia involves various signals traveling from the retina through the choroid to the sclera, eventually resulting in scleral weakening and AXL elongation. The elongation of the AXL occurs, causing light to fail to converge on the retina. This also leads to various complications arising from changes in the posterior segment structures of the eye, including posterior staphyloma and myopic maculopathy, which in turn, contributes to the continual expansion of the globe in the posterior direction.

There are many surgical options available for patients with high myopia. Myopic patients could avoid wearing glasses through corneal laser surgery and Implantable Collamer Lens surgery, which work by flattening the cornea or adding lenses to the anterior chamber to help converge light on the retina. However, these surgeries are purely optical corrections and do not address the pathological changes in the posterior segment structure in myopic eyeballs. Comparatively, traditional PSR surgery aims to strengthen the weakened posterior sclera by ocular patch. The technique was first reported by Shevelev in 1930 and was later modified by Snyder and Thompson. The primary goal of PSR surgery is to reinforce the weakened sclera, not to shorten the AXL to achieve perfect light convergence on the retina. Thus, PSR surgery is particularly essential for patients with high myopia and related complications. In light of the research background, Zhong et al. proposed the concept, that shortening AXL by a novel PSR surgery, is remarkably groundbreaking, potentially allowing for precise and personalized treatment of AXL shortening for patients with high myopia by PSR. Furthermore, traditional macular buckle is primarily used to treat macular schisis in high myopia, addressing the traction on the retina caused by posterior staphyloma in the macular area and promoting the reattachment of the macular schisis. Comparatively, this novel PSR surgery focused more specifically on the shrinkage of the sclera, further reinforcing the weakened sclera through scleral cross-linking (SCXL).

For decades, ocular patch for PSR have consisted of homologous sclera, dura mater and pericardium patches.² In recent years, nonbiological source materials have gained popularity. Researchers have proposed using various hydrogel materials were proposed for PSR, but these studies have remained limited to animal experiments.^{3, 4} Zhong et al. develop

Recently, in Nature Communications, Pan et al.¹ reported a novel dual-functional hydrogel bioadhesive (S-PIL10) based on silk fibroin, ionic liquid, and growth factor TGF-β1, achieving the seamless and dense reconstruction of torn meniscus. This kind of silk-based meniscus adhesive provides a revolutionary strategy for the repair of meniscal tears.

The meniscus, an essential elastic cartilaginous tissue within the knee joint, is between the femoral condyle and the tibial plateau, covering approximately two-thirds of the tibial surface.² It cushions impacts, distributes loads, maintains joint stability, and facilitates smooth joint motion. Meniscal injury is among the most prevalent musculoskeletal disorders affecting the knee, frequently arising from acute traumatic events, sports-related activities (such as sudden pivoting and stopping in basketball and soccer), or age-related degenerative alterations. Based on the pathological morphology of the injury, meniscal tears can be classified into vertical tears (longitudinal and radial tears), horizontal tears (most common), and complex tears (involving multiple tear patterns). These injuries may lead to debilitating symptoms, including pain, swelling, instability, and restricted mobility.^{3, 4} Meniscal injuries primarily affect young individuals, characterized clinically by local bleeding, exudation, and acute inflammation. Left untreated, they may predispose individuals to early-onset osteoarthritis, significantly compromising their quality of life.

In clinical practice, incomplete meniscal tears without accompanying pathologies or small, stable peripheral tears may resolve without surgical intervention. However, the sparse distribution and poor vascularization of meniscal fibrocartilage cells, which occupy only 10%–30% of the meniscal thickness, often impede spontaneous healing, leading to the necessity of surgical intervention in most cases. Current treatment options primarily include meniscal repair, partial or complete meniscectomy, and allograft transplantation. Among these, meniscal repair aims to preserve as much healthy meniscal tissue as possible and is considered the gold standard in clinical practice. However, it is frequently constrained by tear location, size, and tissue quality. Conversely, meniscectomy addresses mechanical irritation from meniscal injury by removing the damaged portion or the entire meniscus. However, post-meniscectomy regeneration is limited, resulting in narrow, thin, and nonfunctional tissue. Although this approach can alleviate related symptoms, biomechanical studies indicate minimal meniscal tissue removal increases cartilage contact stress, reducing the natural meniscus's protective function. Furthermore, the overall failure rate of meniscal allograft transplantation is approximately 29% (4–14 years postoperatively), often accompanied by issues like joint space narrowing

Cardiovascular diseases are the leading cause of mortality which primarily occurs due to the blood vessel obstruction or narrowing. Surgical procedures such as, coronary artery and peripheral artery bypass grafting frequently require vascular grafts for long-term revascularization. However, using autogenous vessels, such as the internal thoracic artery and saphenous vein, especially for vessels with diameters less than 6 mm, are associated with number of concerns due to limited availability, invasive retrieval procedures, and aptness. To overcome these limitations, the development of tissue-engineered vascular grafts (TEVGs) is in continuous thrust. This review comprehensively provides the potentiality of a range of artificial and naturally occurring biopolymers and their fabrication techniques, cell sources and seeding techniques to realize the state-of-the-art TEVGs. Moreover, this review article presents a synopsis of insights obtained from a variety of in vitro and in vivo studies, including human clinical trials. It underscores the need for further exploration into key areas such as optimal cell sources, seeding techniques, mechanical properties, hemodynamics, graft integration, the impact of patient conditions, optimum burst pressure, sufficient suture strength, hydrophilicity, biodegradability, and related factors. In summary, the review offers insights into the current strategies, challenges, and future perspectives of TEVG.

A recent article published in Cell¹ reported that the multiplexed effector guide arrays (MEGA) based on the CRISPR-Cas13d system can contribute to improving chimeric antigen receptor (CAR) T cell exhaustion by massively multiplexed, quantitative, and reversible perturbation of the transcriptome in primary human T cells. This study reminds us that Cas9 may be no longer the dominating force or the only choice in the gene-editing and precision therapy field, and other contenders, including Cas13d, Cas12a as well as numerous unknown systems will come into the fray in not long future.

The successful application of CAR T therapy, as everyone knows, could tremendously benefit tumor-targeted therapy but is plagued by the following challenges, such as T cell exhaustion, cytotoxicity, and off-target effects. To address these issues, Tieu and colleagues developed a MEGA platform by harnessing the Cas13d system that is characterized by the RNA-guide RNA endonuclease activity without PAM sequence recognition, the ability to process poly-crRNA guide arrays to facilitate efficient simultaneous targeting of multiple RNA transcripts in single cells, and the smaller molecular weight compare with Cas9 (Figure 1). First, the authors have succeeded in optimizing MEGA HA-28ζ CAR T cells that robustly suppress the exhaustion marker (LAG3, PD-1, and TIM3) upregulation on transcriptional and surface protein levels and have positively affected the tumor-killing activity of chimeric T cells. Moreover, the MEGA expression and effective processing did not induce interferon (IFN) pathway activation, which is a critical signal for tumor surface recognition of CAR T cells and may be one reason of tumor-killing activity enhancement in chimeric T cells.² More importantly, single-vector bicistronic configurations show that this system has low viral titers, which may benefit from the crRNA-guided cleavage of lentiviral RNA of Cas13d, whereas non-induction of IFN signaling is also extremely important to CAR T cell-mediated cytotoxicity elimination.²

Indeed, previous studies have also provided evidence for CRISPR-Cas9 on pathogenic RNA-targeted elimination and IFN signal inhibition via its powerful gene silencing ability.^{2, 3} Nevertheless, one typical advantage of the MEGA platform is that it can process a long array of nearly 10 targeted genes simultaneously dispensing with independent gRNA guiding, although the knockdown efficiency is uneven when without prior optimization of spacer sequence or position. This has phased significance for data validation of CRISPR-based whole-genome screening or conventional RNA-seq analysis in biological research.^1-3 MEGA provides a powerful example in experimental co-validation of multiple candidate genes in the purinergic signaling and the PI3K/Akt pathway, and its multiplexing capability allows for expendin

This manuscript aims to three-dimensional bioprint and evaluate new polymer composite scaffolds based on synthesized poly(ethylene glycol) dimethacrylate (PEGDMA) as well as methyl cellulose and gelatin. The PEGDMA was synthesized by a simple microwave-assisted method using three distinct molecular weights (MWs) of poly(ethylene glycol) (PEG), 3, 6, and 12 kDa, and methacrylic anhydride. The percent functionalization of the PEGDMA was analyzed using the nuclear magnetic resonance spectrum, and the theoretical calculations indicated that over 50% of methacrylation was achieved in all samples, with the PEGDMA synthesized from 6 kDa PEG surpassing 66% methacrylation. These three PEGDMA-based bioinks were investigated for their suitability for bioprinting scaffolds. It was observed that lower MW PEGDMA resulted in a higher degree of crosslinking, leading to more stable composite scaffolds. However, higher crosslinking degree did not support long-term cell viability when encapsulated with cells. Higher MW PEGDMA showed higher cell viability over time though overall stability was lower. Synthesized PEGDMA with 6 kDa PEG showed both stability and long-term cell viability after postprinting. Over 80% of cell viability was maintained for a 7-day study period, showing potential use in tissue engineering applications as a cell delivery vehicle.

The human skin and mucosal systems build a continuous exterior barrier that encloses the entire body. This natural barrier protects the body by preventing the free entry of a majority of foreign substances, whereas nutrients and selected substances can be transported via either passive or active mechanisms. Unfortunately, the presence of biobarriers also stymies the absorption of therapeutic agents. Breaking through these absorption barriers is one of the leading challenges in modern drug delivery.

The most direct and efficient approach is to breach the barrier by invasive techniques such as injection, microneedle injection, high-pressure powder injection, ionophoresis, and electroporation. However, owing to the well-known safety concerns of barrier damage, noninvasive alternatives with less optimal efficiency are always preferred. The current key issue with noninvasive permeation enhancement is improving the permeation efficiency while preserving the physiological functions of the protective barriers.

Currently, there are a variety of permeation enhancers that act via different mechanisms, including but not limited to small chemicals, polymers, peptide chaperones, and nanovehicles. Among them, chemical permeation enhancers (CPEs) are simple in structure and stable in terms of their physicochemical properties and are therefore easily applicable for different transdermal or trans-mucosal drug delivery purposes. Traditional CPEs such as ethanol, dimethyl sulfoxide, laurocapram, cholates, salcaprozate sodium (SNAC), essential oils, chitosans, etc., function through intricately orchestrated mechanisms of extracting and fluidizing biomembranes or opening intercellular tight junctions. Recent developments in enhancing the oral bioavailability of proteins and peptides by SNAC have highlighted the benefits that CPEs can offer. Nonetheless, debilitating biobarriers by CPEs may cause simultaneous invasion of toxins and pathogens and pose a safety risk. In recent decades, there has been continuous exploration for more potent and safer CPEs. However, dismally, little progress has been made in discovering new types of CPEs. Despite limited success in clinical applications, the development lags far behind the demand for innovative CPEs. Fortunately, the most recent research on transdermal and transmucosal drug delivery has shed light on ionic liquids (ILs) as a unique kind of novel CPE.

ILs are defined as “liquid salts” formed by organic cations and anions through ionic interactions. Unlike solid salts formed by neutralization reactions between a pair of strong acids and bases, one of the cation/anion pairs should be a weak acid or base. Therefore, the interactions in ILs are weaker than the ionic bonds formed in strong acid/base salts, presenting ILs as “liquid salts” with a melting point less than 100°C or ideally at physiological temperatures to address the unmet needs in biomedicines, especially in drug delivery. Notably, there are not

Bone defect is a common clinical disease. Due to the uncertainty of trauma or infection areas, customized size features are often required for bone substitutes. By inspiration of the natural bone structure, this study designs porous scaffolds with a biomimetic design perspective by using different inner and outer pore units. The outer pore units adopt body-centered cubic (BCC) structure to simulate the weight-bearing function of human cortical bone, while inner pore units using I-Wrapped Package structure, a kind of three periods minimum surface, to obtain a good permeability and simulates the inner layer of cancellous bone. To further regulate the overall modulus of the scaffold within the range of natural bone modulus in the human body, the scaffold was designed to axial gradient structure. Compression experiments were conducted, and the results indicated that when the volume fraction linearly increased from 20% to 50%, the Young's modulus was close to the cortical bone modulus in the human body. In vitro cell experiments further proved that osteoblasts have good cellular activity and spreading morphology on the surface of this scaffold. The customized 3D-printed heterogeneous porous titanium scaffold has great application potential in bone tissue engineering.