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Nowadays, biomaterials have evolved from the inert supports or functional substitutes, to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of “biomaterials”, and a typical new insight is the concept of tissue induction biomaterials. The term “regene...
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... sources and applications of regenerative biomaterials are schematically presented in Figure 1. In this paper, we attempt to provide a comprehensive and multidisciplinary insight into regenerative biomaterials, and aim to provide a broad overview of the recent achievements in this exciting field for broader audiences. ...
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... the wound healing progress, sufficient vascularization can avoid many unexpected events such as hypoxia, poor metabolic support and dysregulated immune response that finally lead to chronic wounds [356] 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 deep penetration compared with topical administration [357]. As shown in Figure 10A, miniaturized needle arrays and liquid jet injectors exhibit better drug spatial distribution in the wound bed compared with topical administration, indicating the importance delivery strategy in wound healing. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 A particularly important case to employ biomaterials to enhance pharmaceutics is the development of oral administration [358]. Oral administration of drugs is one of the most popular administration routs for patients, especially for patients with chronic diseases, but used to be regarded inappropriate for biomacromolecular drugs such as proteins, DNA, mRNA owing to their instability in gastrointestinal tract. ...
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... Collins et al. developed a synthetic biology sensor that could be embedded in a wearable material for COVID-19 detection [364]. They unified such a sensor into a mask to detect the potential coronavirus, which may exist in the air ( Figure 11A). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 Another example of medical devises to deal with COVID19 is about extracorporeal membrane oxygenation (ECMO) [365]. Timely and effective supports play a key role in the treatment of COVID-19-related acute hypoxaemic respiratory [366,367]. ...
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... Zhao et al. fabricated an anticoagulant biomimetic gas exchange membrane inspired from the structure of the human alveoli [365]. As shown in Figure 11B, they employed porous metal-organic framework (MOF) particles and CO 2 affinitive hydrophilic polymer to establish the main gas exchange channels, and used polyethersulfone (PES) for mechanical support. ...
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... Pfizer) use lipid nanoparticles for mRNA delivery [374]. As shown in Figure 12 The treatment of COVID-19 mainly depended on antiviral drugs and anti-inflammatory drugs [378][379][380]. The infection of SARS-CoV-2 started with the engagement between the spike protein of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 the virus and the angiotensin-converting enzyme-2 (ACE-2) on host cells [381]. ...
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... is closely related to cell adhesion and migration. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 the effect of the surface modification on cell migration using endothelial cells (ECs) and smooth muscle cells (SMCs) as demonstrated cell types ( Figure 13B) [412]. Their results indicated the celltype-dependent migration peak of RGD nanospacing, which was interpreted from the different resistances to detach a focal adhesion plaque at the trailing edge as well as the different abilities to form a nascent adhesion at the leading edge of a polarized cell on a material. ...
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... the wound healing, M2 macrophages should replace the M1 macrophages (work in the initial stage) to promote tissue repair by releasing anti-inflammatory cytokines, which has inspired the development of an immunomodulatory hydrogel (Figure 14) [450]. The "immune-interactive" biomaterials take advantage of many strategies, including adjusting the pore size, stiffness and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 surface topography of biomaterials, to help the regeneration via regulating macrophages polarization [451,452]. ...
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... there are still challenges in the field of regenerative biomaterials. In our opinion, there are some critical points that should be carefully considered in the future, as schematically presented in Figure 15. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 (1) Creation of new materials is the source of innovation in regenerative biomaterials. ...
Citations
... To mitigate the inflammatory and apoptotic responses induced by different concentrations and exposure durations of carbamide peroxide, it is essential to explore combinatorial approaches. This investigation could focus on strategies such as the co-administration of, for example, anti-inflammatory agents or growth factors to create a more favorable microenvironment that promotes regenerative processes [20,21]. By comprehensively evaluating these combinatorial approaches, we will aim to improve the efficacy and safety of carbamide peroxide applications, ultimately advancing our understanding of regenerative therapies in the context of dental treatment. ...
Background: This study investigated the contact between adult dental pulp stem cells (DPSCs) and carbamide peroxide (CP), a bleaching agent that is a popular choice for at-home whitening products, using an in vitro model. Objectives: The aim of this study was to evaluate the impact of exposure to different concentrations and timings of a commonly used peroxide-based home tooth-whitening product on DPSCs. Materials and methods: Human DPSCs obtained from impacted third molars were cultured and exposed to various concentrations of carbamide peroxide (0.1%, 0.5%, and 1%). The effects of CP on DPSC proliferation and apoptosis were investigated by MTT assay and flow cytometry. Migration was investigated by micrographs of wound healing. An enzyme-linked immunosorbent assay (IL-6 and IL-8) was used to investigate the CP-stimulated cytokine production of DPSCs. Each experiment was performed three times with independent batches of DPSCs. Statistical analysis of the collected data was performed using one-way and two-way ANOVAs with the significance threshold set at p < 0.05. Tukey’s post hoc multiple comparison test was used to identify differences between groups. Results: Cell viability and adherence were lower in the CP-exposed cells compared to the non-stimulated cells, probably due to increased cell death (** p ≤ 0.01, **** p ≤ 0.0001). CP-stimulated DPSCs exhibited a dose-dependent release of IL-6 and IL-8 (**** p ≤ 0.0001). CP did not affect wound healing at any concentration tested. Conclusions: Human DPSCs were able to sense CP. Consequently, CP contributed significantly to cell apoptosis and local inflammatory responses through cytokine release.
... By modifying the activity of the corresponding tissue cells, the physiologically active chemicals found in the ECM are essential for tissue regeneration [29][30][31]. This study analyzed the compositional structure of the epineurium both prior to and following decellularization using proteomics. ...
Following peripheral nerve anastomosis, the anastomotic site is prone to adhesions with surrounding tissues, consequently impacting the effectiveness of nerve repair. This study explores the development and efficacy of a decellularized epineurium as an anti-adhesive biofilm in peripheral nerve repair. Firstly, the entire epineurium was extracted from fresh porcine sciatic nerves, followed by a decellularization process. The decellularization efficiency was then thoroughly assessed. Subsequently, the decellularized epineurium underwent proteomic analysis to determine the remaining bioactive components. To ensure biosafety, the decellularized epineurium underwent cytotoxicity assays, hemolysis tests, cell affinity assays, and assessments of immune response following subcutaneous implantation. Finally, the functionality of the biofilm was determined using a sciatic nerve transection and anastomosis model in rat. The result indicated that the decellularization process effectively removed cellular components from the epineurium while preserving a number of bioactive molecules, and this decellularized epineurium was effective in preventing adhesion while promoting nerve repairment and functional recovery. In conclusion, the decellularized epineurium represents a novel and promising anti-adhesion biofilm for enhancing surgical outcomes of peripheral nerve repair.
... Moreover, there is an increasing focus on translating SCT from preclinical studies to clinical trials and obtaining regulatory approvals. International collaborations are crucial to fostering knowledge sharing and accelerating advancements in SCT for orthopaedics [39][40][41]. ...
The research field of stem cell-based therapies in orthopaedics has witnessed significant growth in the recent past. We aimed to identify and analyze the bibliometric characteristics of the global highly cited papers (HCPs) in stem cell research in orthopaedics.
This study relied on secondary data extracted from Scopus, Elsevier’s abstract and citation database. An advanced search string was employed, for the period from 1995 to 2020. For each paper, the extracted information included the number of citations, title, authors (name, number, authorship position, and country), year of publication, title of the journals, study design, and thematic field. The VOSviewer (1.6.20) was used to uncover relationships between authors, institutions, keywords, and publications.
There were a total of 1427 publications and out of these 186 papers had 100 or more citations (range 100–2644) and were considered as HCPs. The average citation per paper (CPP) was 265.8. Only 4% of the top HCPs contributed 20% of the total citations of all HCPs. All the HCPs were published from high-income countries, and the USA was the leading country in all aspects of publication on stem cell research. Méndez-Ferrer S registered the highest citation (n = 2644), Prockop DJ was the most prolific author (n = 8 papers), and Harvard Medical School, USA emerged as the most prolific organization with 12 HCPs.
Global research in stem cell therapies for orthopaedic problems is making strides, and is an emerging field of research. Stem cell research offers the potential for improved treatment outcomes for various musculoskeletal conditions.
... Furthermore, accessory targeting ligands can be added to the surface of the particles, thereby guiding the particle to bind to a selective cell type, aiding in its precision-targeting capabilities [172][173][174][175]. Specifically, this precisiontargeting ability has been utilized the most within cancer therapeutics, wherein precision in delivering cancer-killing agents is essential [164,[175][176][177]. Hybrid biomaterials are another frontier in the field, combining the properties of multiple materials like metals, ceramics, or polymers to generate delivery vehicles with either a combination of those materials' properties or with entirely new functionalities [178][179][180][181][182][183]. They are most often used to aid in precision targeting because of their controlled release; by using a variety of ingredients to engineer these vehicles, they can be engineered to respond to specific stimuli [184]. Bioprinting technology is the last of these three frontiers and can create three-dimensional scaffolds, which, in the context of protein delivery, can be loaded with proteins and/or growth factors [52]. ...
The development of biomaterials for protein delivery is an emerging field that spans materials science, bioengineering, and medicine. In this review, we highlight the immense potential of protein-delivering biomaterials as therapeutic options and discuss the multifaceted challenges inherent to the field. We address current advancements and approaches in protein delivery that leverage stimuli-responsive materials, harness advanced fabrication techniques like 3D printing, and integrate nanotechnologies for greater targeting and improved stability, efficacy, and tolerability profiles. We also discuss the demand for highly complex delivery systems to maintain structural integrity and functionality of the protein payload. Finally, we discuss barriers to clinical translation, such as biocompatibility, immunogenicity, achieving reliable controlled release, efficient and targeted delivery, stability issues, scalability of production, and navigating the regulatory landscape for such materials. Overall, this review summarizes insights from a survey of the current literature and sheds light on the interplay between innovation and the practical implementation of biomaterials for protein delivery.
... Raw materials for tissue repair and regenerative medicine have been widely investigated [9], for example, polymers like poly (lactide-co-glycolide) (PLGA) [10][11][12][13], poly (lactic acid) [14,15], gelatin [6,16,17] and polytetrafluoroethylene [18,19], metals like iron [20][21][22], magnesium [23] and titanium [24], and other inorganic materials like calcium phosphate ceramics [25,26] and even carbon nanotubes [27]. The fabricating strategy should adapt to the nature of the raw material. ...
Tissue engineering has emerged as an advanced strategy to regenerate various tissues using different raw materials, and thus it is desired to develop more approaches to fabricate tissue engineering scaffolds to fit specific yet very useful raw materials such as biodegradable aliphatic polyester like poly (lactide-co-glycolide) (PLGA). Herein, a technique of ‘wet 3D printing’ was developed based on a pneumatic extrusion three-dimensional (3D) printer after we introduced a solidification bath into a 3D printing system to fabricate porous scaffolds. The room-temperature deposition modeling of polymeric solutions enabled by our wet 3D printing method is particularly meaningful for aliphatic polyester, which otherwise degrades at high temperature in classic fuse deposition modeling. As demonstration, we fabricated a bilayered porous scaffold consisted of PLGA and its mixture with hydroxyapatite for regeneration of articular cartilage and subchondral bone. Long-term in vitro and in vivo degradation tests of the scaffolds were carried out up to 36 weeks, which support the three-stage degradation process of the polyester porous scaffold and suggest faster degradation in vivo than in vitro. Animal experiments in a rabbit model of articular cartilage injury were conducted. The efficacy of the scaffolds in cartilage regeneration was verified through histological analysis, micro-computed tomography (CT) and biomechanical tests, and the influence of scaffold structures (bilayer versus single layer) on in vivo tissue regeneration was examined. This study has illustrated that the wet 3D printing is an alternative approach to biofabricate tissue engineering porous scaffolds based on biodegradable polymers.
... To address this limitation, synthetic polymers can be improved through the addition of signaling biomolecules like glycans, peptides, and growth factors. 103 The application of hydrogels as ECM mimics necessitates a thorough understanding of the cell's native environment. The interactions between cells and their microenvironments are crucial for various processes essential for homeostasis, tissue growth, and regeneration. ...
Cell migration is vital for many fundamental biological processes and human pathologies throughout our life. Dynamic molecular changes in the tissue microenvironment determine modifications of cell movement, which can be reflected either individually or collectively. Endothelial cell (EC) migratory adaptation occurs during several events and phenomena, such as endothelial injury, vasculogenesis, and angiogenesis, under both normal and highly inflammatory conditions. Several advantageous processes can be supported by biomaterials. Endothelial cells are used in combination with various types of biomaterials to design scaffolds promoting the formation of mature blood vessels within tissue engineered structures. Appropriate selection, in terms of scaffolding properties, can promote desirable cell behavior to varying degrees. An increasing amount of research could lead to the creation of the perfect biomaterial for regenerative medicine applications. In this review, we summarize the state of knowledge regarding the possible systems by which inflammation may influence endothelial cell migration. We also describe the fundamental forces governing cell motility with a specific focus on ECs. Additionally, we discuss the biomaterials used for EC culture, which serve to enhance the proliferative, proangiogenic, and promigratory potential of cells. Moreover, we introduce the mechanisms of cell movement and highlight the significance of understanding these mechanisms in the context of designing scaffolds that promote tissue regeneration.
... This may be attributed to the massive Sr 2+ substitution for relatively small Ca 2+ , thus contributing towards the tighter atomic packing of the structure and slowed formation of crystals [31]. Additionally, when used as a biomaterial, the creation of pores is very advantageous since it would allow for the circulation of biological fluids [32]. According to Abifarin et al., with a rise in temperature, SEM micrographs revealed a dense microstructure of HAp particles. ...
... The latest decade has witnessed much progress in biomaterials for medical devices and pharmaceutics etc (33)(34)(35)(36)(37)(38)(39). Among various biomaterials (40)(41)(42), a cardiovascular stent is of much importance in clinics and has much di culty in technique. An ideal stent appropriate for interventional treatment is expected to be highly deliverable with a thin-strut, low pro le, exible design and high radial strength (43). ...
While chronic limb-threatening ischemia is a serious peripheral artery disease, the lack of an appropriate stent significantly limits the potential of interventional treatment. In spite of much progress in coronary stents, little is towards peripheral stents, which are expected to be long and biodegradable and thus require more breakthroughs in core techniques. Herein, we develop a long & biodegradable stent (LBS) with a length of up to 118 mm based on a metal-polymer composite material. Nitriding treated iron with elevated mechanical performance was applied as the skeleton of the stent, and a polylactide coating was used to accelerate iron degradation. To achieve a well-prepared homogeneous coating on a long stent during ultrasonic spraying, a magnetic levitation (Maglev) was employed. In vivo degradation of the LBS was investigated in rabbit abdominal aorta/iliac arteries, and preclinical safety and efficacy were evaluated in canine infrapopliteal arteries. First-in-man implantation of LBS was carried out in the below-the-knee artery, and the 6–13 months follow-ups demonstrated the feasibility of the first LBS.
... However, slow corrosion rates have hindered the development of Fe-based materials [4][5][6][7]. To this day, various alloying [8][9][10], surface modification [11][12][13], and advanced manufacturing [14,15] methods have been used to regulate the degradation behavior of Fe-based alloys. ...
Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable biocompatibility. Currently, research on Fe-based materials mainly focuses on regulating the degradation rate. However, excessive release of Fe ions during material degradation will induce the generation of reactive oxygen species (ROS), leading to oxidative stress and ferroptosis. Therefore, the control of ROS release and the improvement of biocompatibility for Fe-based materials are very important. In this study, new Fe-Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy degradation. Initially, the impact of three potential degradation ions (Fe2+, Fe3+, Zn2+) from the Fe-Zn alloy on human endothelial cells’ (ECs) activity and migration ability was investigated. Subsequently, cell adhesion, cell activity, ROS production, and DNA damage were assessed at various locations surrounding the alloy. Finally, the influence of different concentrations of Zn2+ in the medium on cell viability and ROS production was evaluated. High levels of ROS exhibited evident toxic effects on ECs and promoted DNA damage. As an antioxidant, Zn2+ effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/L. These findings demonstrate that Fe-Zn alloy can attenuate the ROS generated from Fe degradation thereby enhancing cytocompatibility.
... Cells maintain extensive connections to their extracellular matrix (ECM) microenvironment, and their behaviors can be modulated by a variety of physical, chemical, and mechanical stimuli present in their surroundings [1][2][3][4][5][6][7][8][9][10][11][12]. The heightened sensitivity of cells to the mechanical and biochemical properties of their external microenvironment highlights the inadequacy of conventional cell culture platforms, underscoring the need for culture models with enhanced physiological relevance [13,14]. ...
Micropatterns, characterized as distinct physical microstructures or chemical adhesion matrices on substance surfaces, have emerged as a powerful tool for manipulating cellular activity. By creating specific extracellular matrix microenvironments, micropatterns can influence various cell behaviors, including orientation, proliferation, migration, and differentiation. This review provides a comprehensive overview of the latest advancements in the use of micropatterns for cell behavior regulation. It discusses the influence of micropattern morphology and coating on cell behavior and the underlying mechanisms. It also highlights future research directions in this field, aiming to inspire new investigations in materials medicine, regenerative medicine, and tissue engineering. The review underscores the potential of micropatterns as a novel approach for controlling cell behavior, which could pave the way for breakthroughs in various biomedical applications.
