Local bone metabolism balance regulation via double-adhesive hydrogel for fixing orthopedic implants

© 2021 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)The effective osteointegration of orthopedic implants is a key factor for the success of orthopedic surgery. However, local metabolic imbalance around implants under osteoporosis condition could jeopardize the fixation effect. Inspired by the bone structure and the composition around implants under osteoporosis condition, alendronate (A) was grafted onto methacryloyl hyaluronic acid (H) by activating the carboxyl group of methacryloyl hyaluronic acid to be bonded to inorganic calcium phosphate on trabecular bone, which is then integrated with aminated bioactive glass (AB) modified by oxidized dextran (O) for further adhesion to organic collagen on the trabecular bone. The hybrid hydrogel could be solidified on cancellous bone in situ under UV irradiation and exhibits dual adhesion to organic collagen and inorganic apatite, promoting osteointegration of orthopedic implants, resulting in firm stabilization of the implants in cancellous bone areas. In vitro, the hydrogel was evidenced to promote osteogenic differentiation of embryonic mouse osteoblast precursor cells (MC3T3-E1) as well as inhibit the receptor activator of nuclear factor-κ B ligand (RANKL)-induced osteoclast differentiation of macrophages, leading to the upregulation of osteogenic-related gene and protein expression. In a rat osteoporosis model, the bone-implant contact (BIC) of the hybrid hydrogel group increased by 2.77, which is directly linked to improved mechanical stability of the orthopedic implants. Overall, this organic-inorganic, dual-adhesive hydrogel could be a promising candidate for enhancing the stability of orthopedic implants under osteoporotic conditions.This work was supported by the National Key R&D Program of China (2020YFA0908200), National Natural Science Foundation of China (82120108017), Six talent peaks project in Jiangsu Province (WSW-018). This work was financed by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” UID/BIM/04293/2019.info:eu-repo/semantics/publishedVersio

A pH-Responsive Cluster Metal-Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect

As a result of the deficient tumor-specific antigens, potential off-target effect, and influence of protein corona, metal–organic framework nanoparticles have inadequate accumulation in tumor tissues, limiting their therapeutic effects. In this work, a pH-responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3-(bromomethyl)-4-methyl-2,5-furandione (MMfu) and poly(ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nanoshell to coat apilimod (Ap)-loaded zeolitic imidazolate framework (Ap-ZIF) to form Ap-ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap-ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap-ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap-ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor-bearing mice after injections with Ap-ZIF@SLN#TL. Furthermore, mice show normal tissue structure of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH-responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects.</p

Electrospun fiber‐based immune engineering in regenerative medicine

Abstract Immune engineering, a burgeoning field within regenerative medicine, involves a spectrum of strategies to optimize the intricate interplay between tissue regenerative biomaterials and the host tissue. These strategies are applied across different types of biomaterials and various disease models, which encompasses finely modulating the immune response at the levels of immune cells and factors, aiming to mitigate adverse effects like fibrosis and persistent inflammation that may arise at the injury site and consequently promote tissue regeneration. With the continuous progress in electrospinning technology, the immunoregulatory capabilities of electrospun fibers have gained substantial attention over the years. Electrospun fibers, with their extracellular matrix‐like characteristics, high surface‐area‐to‐volume ratio, and reliable pharmaceutical compound capacity, have emerged as key players among tissue engineering materials. This review specifically focuses on the role of electrospun fiber‐based immune engineering, emphasizing their unique design strategies. Notably, electrospinning actively engages in immune engineering by modulating immune responses through four essential strategies: (i) surface modification, (ii) drug loading, (iii) physicochemical parameters, and (iv) biological grafting. This review presents a comprehensive overview of the intricate mechanisms of the immune system in injured tissues while unveiling the key strategies adopted by electrospun fibers to orchestrate immune regulation. Furthermore, the review explores the current developmental trends and limitations concerning the immunoregulatory function of electrospun fibers, aiming to drive the advancements in electrospun fiber‐based immune engineering to its full potential

Association of cesarean delivery timing with pelvic floor muscle function and urine incontinence: A propensity score‐matched study

Abstract Pelvic floor dysfunction is a common gynecological disease that adversely affects women's quality of life and mental health. Delivery is considered a significant independent risk factor for pelvic floor dysfunction. Surface electromyography (sEMG) values for the pelvic floor muscles (PFM) have been shown to differ according to different delivery modes. This study aimed to compare sEMG results between intrapartum and antepartum cesarean delivery (CD), 42–60 days after delivery. Data of women who underwent CD at the International Peace Maternity and Child Health Hospital were collected from September 2021 to December 2021. Myotrac Infiniti System was used to measure the electromyographic activity of PFM after 42–60 days of parturition. Propensity score matching (1:1) was applied to achieve a balance in baseline data between the two groups (intrapartum and antepartum CD). A total of 200 paired cases were selected for statistical analysis. In the propensity score‐matched analysis, there were no statistically significant differences in PFM sEMG between women with antepartum or intrapartum CD (p > 0.05 for all). We observed similar results with postpartum urinary incontinence (24 [12.0] vs. 21 [10.5]; adjusted odds ratio (aOR), 1.12 [95% confidence interval (CI) 0.60–2.12]; p = 0.717) and stress urinary incontinence (12 [6.0] vs. 14 [7.0]; aOR, 0.80 [95% CI 0.35–1.80]; p = 0.596) as outcomes. After excluding participants with intrapartum CD when the cervix was dilated <6 cm, all sEMG of PFM had a comparable level of risk in both the antepartum and intrapartum CD groups. There were no significant differences in sEMG of the PFM and the incidence of urinary incontinence between patients undergoing intrapartum or antepartum CD. Excluding women who underwent intrapartum CD when the cervix was dilated to <6 cm produced little change in results. Thus, different opportunities for CD may not impact the sEMG of the PFM and the incidence of urinary incontinence

Abdominal wall hernia repair: from prosthetic meshes to smart materials

Hernia reconstruction is one of the most frequently practiced surgical procedures worldwide. Plastic surgery plays a pivotal role in reestablishing desired abdominal wall structure and function without the drawbacks traditionally associated with general surgery as excessive tension, postoperative pain, poor repair outcomes, and frequent recurrence. Surgical meshes have been the preferential choice for abdominal wall hernia repair to achieve the physical integrity and equivalent components of musculofascial layers. Despite the relevant progress in recent years, there are still unsolved challenges in surgical mesh design and complication settlement. This review provides a systemic summary of the hernia surgical mesh development deeply related to abdominal wall hernia pathology and classification. Commercial meshes, the first-generation prosthetic materials, and the most commonly used repair materials in the clinic are described in detail, addressing constrain side effects and rational strategies to establish characteristics of ideal hernia repair meshes. The engineered prosthetics are defined as a transit to the biomimetic smart hernia repair scaffolds with specific advantages and disadvantages, including hydrogel scaffolds, electrospinning membranes, and three-dimensional patches. Lastly, this review critically outlines the future research direction for successful hernia repair solutions by combing state-of-the-art techniques and materials

Capturing dynamic biological signals via bio-mimicking hydrogel for precise remodeling of soft tissue

Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell behavior. However, capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological processes. Here, a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation, and the chemical signals provided with chemokine and natural adhesion sites, which guaranteed the precise soft tissue remodeling. This bio-mimicking hydrogel efficiently facilitated cell anchoring, migration, and invasion in the 3D matrix due to the permissive space and the interaction with integrin receptors. Besides, the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1α dependent signal pathway. Furthermore, the early polarization of macrophages, collagen deposition and angiogenesis in rat acute wound model, and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve, myocardium, and even bone

Geometric Angles and Gene Expression in Cells for Structural Bone Regeneration

Abstract Geometry and angles play crucial roles in cellular processes; however, its mechanisms of regulation remain unclear. In this study, a series of three dimensional (3D)‐printed microfibers with different geometries is constructed using a near‐field electrostatic printing technique to investigate the regulatory mechanisms of geometry on stem cell function and bone regeneration. The scaffolds precisely mimicked cell dimensions with high porosity and interoperability. Compared with other spatial topography angles, microfibers with a 90° topology can significantly promote the expression of osteogenic gene proteins in bone marrow‐derived mesenchymal stem cells (BMSCs). The effects of different spatial structures on the expression profiles of BMSCs differentiation genes are correlated and validated using microRNA sequencing. Enrichment analysis shows that the 90° microfibers promoted osteogenesis in BMSCs by significantly upregulating miR‐222‐5p/cbfb/Runx2 expression. The ability of the geometric architecture to promote bone regeneration, as assessed using the cranial defect model, demonstrates that the 90° fiber scaffolds significantly promote new bone regeneration and neovascular neural network formation. This study is the first to elucidate the relationship between angular geometry and cellular gene expression, contributing significantly to the understanding of how geometric architecture can promote stem cell differentiation, proliferation, and function for structural bone regeneration

Reprogramming stem cells in regenerative medicine

Abstract Induced pluripotent stem cells (iPSCs) that are generated from adult somatic cells are induced to express genes that make them pluripotent through reprogramming techniques. With their unlimited proliferative capacity and multifaceted differentiation potential and circumventing the ethical problems encountered in the application of embryonic stem cells (ESC), iPSCs have a broad application in the fields of cell therapy, drug screening, and disease models and may open up new possibilities for regenerative medicine to treat diseases in the future. In this review, we begin with different reprogramming cell technologies to obtain iPSCs, including biotechnological, chemical, and physical modulation techniques, and present their respective strengths, and limitations, as well as the recent progress of research. Secondly, we review recent research advances in iPSC reprogramming‐based regenerative therapies. iPSCs are now widely used to study various clinical diseases of hair follicle defects, myocardial infarction, neurological disorders, liver diseases, and spinal cord injuries. This review focuses on the translational clinical research around iPSCs as well as their potential for growth in the medical field. Finally, we summarize the overall review and look at the potential future of iPSCs in the field of cell therapy as well as tissue regeneration engineering and possible problems. We believe that the advancing iPSC research will help drive long‐awaited breakthroughs in cellular therapy