Tissue regeneration and remodeling involve many complex stages. Macrophages are critical in maintaining micro-environmental homeostasis by regulating inflammation and orchestrating wound healing. They display high plasticity in response to various stimuli, showing a spectrum of functional phenotypes that vary from M1 (pro-inflammatory) to M2 (anti-inflammatory) macrophages. While transient inflammation is an essential trigger for tissue healing following an injury, sustained inflammation (e.g., in foreign body response to implants, diabetes or inflammatory diseases) can hinder tissue healing and cause tissue damage. Modulating macrophage polarization has emerged as an effective strategy for enhancing immune-mediated tissue regeneration and promoting better integration of implantable materials in the host. This article provides an overview of macrophages\' functional properties followed by discussing different strategies for modulating macrophage polarization. Advances in the use of synthetic and natural biomaterials to fabricate immune-modulatory materials are highlighted. This reveals that the development and clinical application of more effective immunomodulatory systems targeting macrophage polarization under pathological conditions will be driven by a detailed understanding of the factors that regulate macrophage polarization and biological function in order to optimize existing methods and generate novel strategies to control cell phenotype.

This paper reports on the coating of heterostructured TiO2 nanopores/nanotubes on Ti substrates by anodizing at high voltages to design surfaces for biomedical implants. As the anodized voltage from 50 V to 350 V was applied, the microstructure of the coating shifted from regular TiO2 nanotubes to heterostructured TiO2 nanopores/nanotubes. In addition, the dimension of the heterostructured TiO2 nanopores/nanotubes was a function of voltage. The electrochemical characteristics of TiO2 nanotubes and heterostructured TiO2 nanopores/nanotubes were evaluated in simulated body fluid (SBF) solution. The creation of heterostructured TiO2 nanopores/nanotubes on Ti substrates resulted in a significant increase in BHK cell attachment compared to that of the Ti substrates and the TiO2 nanotubes.

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UNASSIGNED: Successful diabetes reversal using pancreatic islet transplantation by various groups illustrates the significant achievements made in cell-based diabetes therapy. While clinically, intraportal islet delivery is almost exclusively used, it is not without obstacles, including instant blood-mediated inflammatory reaction (IBMIR), relative hypoxia, and loss of function over time, therefore hindering long-term success. Here we demonstrate the perihepatic surface of non-human primates (NHPs) as a potential islet delivery site maximizing favorable characteristics, including proximity to a dense vascular network for adequate oxygenation while avoiding IBMIR exposure, maintenance of portal insulin delivery, and relative ease of accessibility through minimally invasive surgery or percutaneous means. In addition, we demonstrate a targeted mapping technique of the perihepatic surface, allowing for the testing of multiple experimental conditions, including a semi-synthetic hydrogel as a possible three-dimensional framework to improve islet viability.
UNASSIGNED: Perihepatic allo-islet cell transplants were performed in immunosuppressed cynomolgus macaques using a targeted mapping technique to test multiple conditions for biocompatibility. Transplant conditions included islets or carriers (including hydrogel, autologous plasma, and media) alone or in various combinations. Necropsy was performed at day 30, and histopathology was performed to assess biocompatibility, immune response, and islet viability. Subsequently, single-injection perihepatic allo-islet transplant was performed in immunosuppressed diabetic cynomolgus macaques. Metabolic assessments were measured frequently (i.e., blood glucose, insulin, C-peptide) until final graft retrieval for histopathology.
UNASSIGNED: Targeted mapping biocompatibility studies demonstrated mild inflammatory changes with islet-plasma constructs; however, significant inflammatory cell infiltration and fibrosis were seen surrounding sites with the hydrogel carrier affecting islet viability. In diabetic NHPs, perihepatic islet transplant using an autologous plasma carrier demonstrated prolonged function up to 6 months with improvements in blood glucose, exogenous insulin requirements, and HbA1c. Histopathology of these islets was associated with mild peri-islet mononuclear cell infiltration without evidence of rejection.
UNASSIGNED: The perihepatic surface serves as a viable site for islet cell transplantation demonstrating sustained islet function through 6 months. The targeted mapping approach allows for the testing of multiple conditions simultaneously to evaluate immune response to biomaterials at this site. Compared to traditional intraportal injection, the perihepatic site is a minimally invasive approach that allows the possibility for graft recovery and avoids IBMIR.

Elastin, a fibrous extracellular matrix (ECM) protein, is the main component of elastic fibers that are involved in tissues\' elasticity and resilience, enabling them to undergo reversible extensibility and to endure repetitive mechanical stress. After wounding, it is challenging to regenerate elastic fibers and biomaterials developed thus far have struggled to induce its biosynthesis. This review provides a comprehensive summary of elastic fibers synthesis at the cellular level and its implications for biomaterial formulation, with a particular focus on dermal substitutes. The review delves into the intricate process of elastogenesis by cells and investigates potential triggers for elastogenesis encompassing elastin-related compounds, ECM components, and other molecules for their potential role in inducing elastin formation. Understanding of the elastogenic processes is essential for developing biomaterials that trigger not only the synthesis of the elastin protein, but also the formation of a functional and branched elastic fiber network.

Autologous cancer vaccines represent a promising therapeutic approach against tumor relapse. Herein, a concise biomineralization strategy was developed to prepare an immunostimulatory autologous cancer vaccine through protein antigen-mediated growth of flower-like manganese phosphate (MnP) nanoparticles. In addition to inheriting the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING)-activating capacity of Mn2+, the resulting ovalbumin (OVA)-loaded MnP (OVA@MnP) nanoparticles with superior stability and pH-responsiveness enabled efficient priming of antigen-specific CD8+ T cell expansion through promoting the endo/lysosome escape and subsequent antigen cross-presentation of OVA. Resultantly, OVA@MnP vaccines upon subcutaneous vaccination elicited both prophylactic and therapeutic effects against OVA-expressing B16-F10 melanoma. Furthermore, the biomineralized autologous cancer vaccines prepared from the whole tumor cell lysates of the dissected tumors suppressed the growth of residual tumors, particularly in combination with anti-PD-1 immunotherapy. This study highlights a simple biomineralization approach for the controllable synthesis of cGAS-STING-activating autologous cancer vaccines to suppress postsurgical tumor relapse.

Several abdominal-located cancers develop metastasis within the peritoneum, what is called peritoneal carcinomatosis (PC), constituting a clinical challenge in their therapeutical management, often leading to poor prognoses. Current multidisciplinary strategies, including cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC), demonstrate efficacy but have limitations. In response, alternative strategies are explored in the drug delivery field for intraperitoneal chemotherapy. Controlled drug delivery offers a promising avenue, maintaining localized drug concentrations for optimal PC management. Drug delivery systems (DDS), including hydrogels, implants, nanoparticles, and hybrid systems, show potential for sustained and region-specific drug release. The present review aims to offer an overview of the advances and current designs of DDS for PC chemotherapy administration, focusing on their composition, main characteristics, and principal experimental outcomes, highlighting the importance of biomaterial rationale design and in vitro/vivo models for their testing. Moreover, since clinical data for human subjects are scarce, we offer a critical discussion of the gap between bench and bedside in DDS translation, emphasizing the need for further research.

Over the past three decades, cell therapy development has fallen short of expectations, with many cellular sources demonstrating a \"Janus effect\" and raising safety concerns. Extracellular vesicles (EVs), supported by advanced technologies, present a promising avenue in regenerative medicine, offering benefits such as immune tolerance and avoidance of negative aspects associated with cell transplants. Our previous research showcased enhanced and organized subcutaneous vascularization using three-dimensional bioprinted patches containing HUVEC-derived EVs in immunodeficient animal models. In this context, stress conditions on the cells of origin further boosted the EVs\' neoangiogenic potential. Since neovascularization is the first regenerative target requiring restoration, the present study aims to complement our previous work by employing an injectable gelatin methacrylate (GelMA) hydrogel functionalized with HUVEC-derived EVs in a pathological condition of acute myocardial infarction. This bioactive hydrogel resulted in reduced fibrosis, improved contractility, and promoted angiogenesis, showing promise in countering tissue deterioration and addressing vascular deficits. Moreover, the molecular characterization of EVs through miRNome and proteomic analyses further supports their potential as bio-additives for hydrogel functionalization. This cell-free approach mitigates immune rejection and oncogenic risks, offering innovative therapeutic advantages.

Ulva, a genus of green macroalgae commonly known as sea lettuce, has long been recognized for its nutritional benefits for food and feed. As the demand for sustainable food and feed sources continues to grow, so does the interest in alternative, plant-based protein sources. With its abundance along coastal waters and high protein content, Ulva spp. have emerged as promising candidates. While the use of Ulva in food and feed has its challenges, the utilization of Ulva in other industries, including in biomaterials, biostimulants, and biorefineries, has been growing. This review aims to provide a comprehensive overview of the current status, challenges and opportunities associated with using Ulva in food, feed, and beyond. Drawing on the expertise of leading researchers and industry professionals, it explores the latest knowledge on Ulva\'s nutritional value, processing methods, and potential benefits for human nutrition, aquaculture feeds, terrestrial feeds, biomaterials, biostimulants and biorefineries. In addition, it examines the economic feasibility of incorporating Ulva into aquafeed. Through its comprehensive and insightful analysis, including a critical review of the challenges and future research needs, this review will be a valuable resource for anyone interested in sustainable aquaculture and Ulva\'s role in food, feed, biomaterials, biostimulants and beyond.

BACKGROUND: Different protocols and procedures for sinus lift and implant placement are available, generally involving the use of grafts to increase the tissue volume and/or prevent the Schneiderian membrane from collapsing. Among xenografts, deproteinised bovine bone graft (DBBP) is frequently used in sinus lift procedures. Leaving an ungrafted space following membrane elevation has proven to have a bony regenerative potential as well. This study aimed to compare the clinical and histological features of sinus lift surgery performed with or without biomaterials.
METHODS: Patients with severe maxillary posterior atrophy (residual bone height 2-6 mm and residual crest thickness ≥4 mm), and in need of sinus lift surgery to allow the placement of three implants were enrolled and randomly divided into two groups. They underwent sinus lifts with DBBP (control) or with a graftless technique (test) and immediate placement of two implants (a mesial and distal one). After 6 months, a bone sample was retrieved from the area between the previously inserted fixtures, and a third, central implant was placed. The collected bone samples were analyzed morphologically and histomorphometrically. The patients were provided with prosthetic restorations after 6 months and followed up for 5-12 years.
RESULTS: Ten patients were enrolled in the test and nine in the control group. The 6-month follow-up showed in the control group an average augmentation of 10.31 mm (±2.12), while in the test group it was 8.5 mm (±1.41) and a success rate of 96.3% in the control and 86.7% in the test group (p > 0.05). The histological analysis evidenced the presence of new bone tissue surrounded by immature osteoid matrix in the test group, and a variable number of DBBP particles surrounded by an immature woven bone matrix in the control group.
CONCLUSIONS: The results of the present trial indicate that, with residual bone height of 2-6 mm and residual crest thickness ≥4 mm, sinus lift surgery with or without biomaterials followed by implant restoration, produces similar clinical and histological outcomes.