Tissue Engineering. Part B, Reviews最新文献

Synthetic bone transplantation has emerged in recent years as a highly promising strategy to address the major clinical challenge of bone tissue defects. In this field, bioactive glasses (BGs) have been widely recognized as a viable alternative to traditional bone substitutes due to their unique advantages, including favorable biocompatibility, pronounced bioactivity, excellent biodegradability, and superior osseointegration properties. This article begins with a comprehensive overview of the development and success of BGs in bone tissue engineering, and then focuses on their composite reinforcement systems with biodegradable metals, calcium-phosphorus (Ca-P)-based bioceramics, and biodegradable medical polymers, respectively. Moreover, the article outlines some frequently used manufacturing methods for three-dimensional BG-based bone bioscaffolds and highlights the remarkable achievements of these scaffolds in the field of bone defect repair in recent years. Lastly, based on the many potential challenges encountered in the preparation and application of BGs, a brief outlook on their future directions is presented. This review may help to provide new ideas for researchers to develop ideal BG-based bone substitutes for bone reconstruction and functional recovery.

Conditions such as congenital abnormalities, cancer, infections, and trauma can severely impact the integrity of the auricular cartilage, resulting in the need for a replacement structure. Current implants, carved from the patient's rib, involve multiple surgeries and carry risks of adverse events such as contamination, rejection, and reabsorption. Tissue engineering aims to develop lifelong auricular bioimplants using different methods, different cell types, growth factors and maintenance media formulations, and scaffolding materials compatible with the host. This review aims to examine the progress in auricular bioengineering, focusing on improvements derived from in vivo models and clinical trials, as well as the author's suggestions to enhance the methods. For this scope review, 30 articles were retrieved through Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, plus 6 manually selected articles. The methods reported in the articles were categorized into four levels according to the development phases: source of cells, cell media supplementation, scaffold, or scaffold-free methods, and experimental in vivo or clinical approaches. Many methods have demonstrated potential for the development of bioimplants; four clinical trials reported a structure like the external ear that could be maintained after overcoming post-transplant inflammation. However, several challenges must be solved, such as obtaining a structure that accurately replicates the shape and size of the patient's healthy contralateral auricle and improvements to avoid immunological rejection and resorption of the bioimplant.

Three-dimensional printing (3DP) strategies in the field of meniscus and articular disc repair and regeneration have recently garnered significant attention. However, a comprehensive bibliometric assessment to evaluate the scientific progress in this area is lacking. This research aims to explore the development, key areas of focus, and new directions in 3DP techniques for meniscus and articular disc over the last 15 years, considering both structural and temporal perspectives. Academic papers on 3DP approaches for the repair and regeneration of these tissues were retrieved from the Web of Science Core Collection. Bibliometric analysis tools such as R software, CiteSpace, and VOSviewer were utilized to examine the historical patterns, topic evolution, and emerging trends in this domain. For the past 15 years, there has been a steady increase in scholarly attention toward 3DP for the repair of meniscus and articular discs, along with a notable expansion in impactful scientific partnerships. The timeline analysis of references indicates that 3DP methodologies have predominantly shaped the research agenda over the last 10 years, retaining their significance amid annual fluctuations in the focus of citations. Four emerging research subfields were identified through keyword clustering: "mesenchymal stem cells," "fabrication," "scaffolds," and "cartilage." Additionally, we mapped out the top 13 key clusters based on CiteSpace. The time zone view of keyword analysis identified three emerging research niches: "anti-inflammatory and antioxidant," "chondrogenic differentiation," and "silk-based biomaterial-ink." The insights gleaned from these bibliometric studies highlight the current state and trends in 3DP research for meniscus and articular disc, potentially assisting researchers in identifying key focal points and pioneering innovative research directions within this area.

Photoaged skin features an appearance of premature aging induced by external factors, mainly ultraviolet (UV) irradiation. Visible aging signs and increased susceptibility to skin-related diseases triggered by UV irradiation have raised widespread concern. As a critical component of human skin, the extracellular matrix (ECM) provides essential structural, mechanical, and functional support to the tissue. Consequently, UV-induced ECM deterioration is a major contributor to photoaging. This review begins by analyzing the structural and functional changes between healthy and photoaged skin in prominent ECM components, including collagens, glycosaminoglycans (GAGs), proteoglycans, basement membrane proteins, and elastic fibers. Furthermore, we explore the key mechanisms driving ECM deterioration in response to UV irradiation, focusing on mitogen-activated protein kinase/matrix metalloproteinase and transforming growth factor-β/Smad signaling pathways, as well as the synthesis and degradation of GAGs. A comprehensive understanding of these changes and underlying mechanisms is crucial for elucidating the biological influence of UV on the ECM, ultimately providing more reliable evidence for the prevention and treatment of skin photoaging.

Epicatechin (EC)-based derivatives have garnered significant attention for their powerful antioxidant, anti-inflammatory, anticancer, and antibacterial properties, all of which are attributed to the phenolic hydroxyl groups in their structure. These compounds are promising in regenerative medicine, particularly as bioactive components in scaffolds. This review provides an in-depth analysis of the mechanisms by which EC-based materials enhance tissue repair, examining their application in various scaffold forms, such as hydrogels, nanoparticles, and nanofibers. This study also addresses the challenges of stability and bioavailability associated with ECs and proposes encapsulation techniques to overcome these barriers. The potential clinical benefits of ECs in regenerative medicine and their role in fostering advancements in tissue engineering are discussed, making this review a valuable resource for guiding future studies on the integration of ECs into clinical practice.

The main focus of this article is the role of lipids in biomineralization. Much of the discussion on biomineralization focuses on proteins in these decades. Indeed, collagen and acidic noncollagenous proteins effectively serve as templates for mineralization. However, other macromolecules such as lipids and polysaccharides have received less attention despite their abundance at mineralization sites. The matrix vesicle (MV) theory is widely accepted as the induction of early mineralization. Although ion concentration within the vesicles has been discussed in the initial mineralization in this theory, the role of phospholipids that constitute the vesicle membrane has not been discussed much. Comprehensive considerations, including pathological mineralization, exist regardless of the localization of MVs, the involvement of bacteria in dental calculus formation, and biomineralization caused by marine organisms such as corals, suggesting that initial mineralization found in these biological conditions might be a common reaction relating to lipids. In contrast, despite the abundance of lipids, mineralization occurs only in the limited tissue within our body. In other words, gathering knowledge and creating a path to understanding about lipid-based mineralization is extremely important in proposing new bone disease treatment methods. This article describes how lipids influence nucleation, mineralization, and expansion during hard tissue formation. Impact statement Recent studies have accumulated evidence of mineralization involving phospholipids and the matrix vesicle (MV) theory. Mineralization occurs not only in the conventional vesicle form but also in flat membranes arrested by the matrix. The flat membrane is derived not only from MVs but also from various causes, such as cell rupture and cell apoptosis. Mineralization is greatly affected by alkaline phosphatases derived from cell membranes. By understanding phospholipid-based mineralization, it will be possible to design new mineralization-inducing materials centered on cellular components for early bone formation. This article is important for developing new strategies to induce bone mineralization.

The repair of nasal septal cartilage is a key challenge in cosmetic and functional surgery of the nose, as it determines its shape and its respiratory function. Supporting the dorsum of the nose is essential for both the prevention of nasal obstruction and the restoration of the nose structure. Most surgical procedures to repair or modify the nasal septum focus on restoring the external aspect of the nose by placing a graft under the skin, without considering respiratory concerns. Tissue engineering offers a more satisfactory approach, in which both the structural and biological roles of the nose are restored. To achieve this goal, nasal cartilage engineering research has led to the development of scaffolds capable of accommodating cartilaginous extracellular matrix-producing cells, possessing mechanical properties close to those of the nasal septum, and retaining their structure after implantation in vivo. The combination of a non-resorbable core structure with suitable mechanical properties and a biocompatible hydrogel loaded with autologous chondrocytes or mesenchymal stem cells is a promising strategy. However, the stability and immunotolerance of these implants are crucial parameters to be monitored over the long term after in vivo implantation, to definitively assess the success of nasal cartilage tissue engineering. Here, we review the tissue engineering methods to repair nasal cartilage, focusing on the type and mechanical characteristics of the biomaterials; cell and implantation strategy; and the outcome with regard to cartilage repair. Impact statement Nasal septal cartilage is key to the cosmetic and function of the nose. To repair important damage to the nasal septum, current surgical techniques are complex and limited by graft source availability. Conversely, tissue engineering is a promising strategy to reproduce the dimensions and mechanical properties of the nose without causing donor site morbidity. This approach, however, remains overlooked for the reconstruction of the nasal septum compared with other cartilaginous tissues. This review describes the specific challenges associated with nasal cartilage repair and the pioneering studies leading to advances in the growing field of nose tissue engineering.

Bone defects represent a prevalent category of clinical injuries, causing significant pain and escalating health care burdens. Effectively addressing bone defects is thus of paramount importance. Platelets, formed from megakaryocyte lysis, have emerged as pivotal players in bone tissue repair, inflammatory responses, and angiogenesis. Their intracellular storage of various growth factors, cytokines, and membrane protein receptors contributes to these crucial functions. This article provides a comprehensive overview of platelets' roles in hematoma structure, inflammatory responses, and angiogenesis throughout the process of fracture healing. Beyond their application in conjunction with artificial bone substitute materials for treating bone defects, we propose the potential future use of anticoagulants such as heparin in combination with these materials to regulate platelet number and function, thereby promoting bone healing. Ultimately, we contemplate whether manipulating platelet function to modulate bone healing could offer innovative ideas and directions for the clinical treatment of bone defects. Impact statement Given that 5-10% of fracture patients with delayed bone healing or even bone nonunion, this review explores the potential role of platelets in bone healing (directly/indirectly) and proposes ideas and directions for the future as to whether it is possible to promote bone healing and improve fracture healing rates by modulating platelets.

The foreign body response (FBR) and organ fibrosis are complex biological processes involving the interaction between macrophages and fibroblasts. Understanding the molecular mechanisms underlying macrophage-fibroblast cross talk is crucial for developing strategies to mitigate implant encapsulation, a major cause of implant failure. This article reviews the current knowledge on the role of macrophages and fibroblasts in the FBR and organ fibrosis, highlighting the similarities between these processes. The FBR is characterized by the formation of a fibrotic tissue capsule around the implant, leading to functional impairment. Various factors, including material properties such as surface chemistry, stiffness, and topography, influence the degree of encapsulation. Cross talk between macrophages and fibroblasts plays a critical role in both the FBR and organ fibrosis. However, the precise molecular mechanisms remain poorly understood. Macrophages secrete a wide range of cytokines that modulate fibroblast behavior such as abundant collagen deposition and myofibroblast differentiation. However, the heterogeneity of macrophages and fibroblasts and their dynamic behavior in different tissue environments add complexity to this cross talk. Experimental evidence from in vitro studies demonstrates the impact of material properties on macrophage cytokine secretion and fibroblast physiology. However, the correlation between in vitro response and in vivo encapsulation outcomes is not robust. Adverse outcome pathways (AOPs) offer a potential framework to understand and predict process complexity. AOPs describe causal relationships between measurable events leading to adverse outcomes, providing mechanistic insights for in vitro testing and predictive modeling. However, the development of an AOP for the FBR does require a comprehensive understanding of the molecular initiating events and key event relationships to identify which events are essential. In this article, we describe the current knowledge on macrophage-fibroblast cross talk in the FBR and discuss how targeted research can help build an AOP for implant-related fibrosis. Impact statement Biomaterials are widely used to manufacture medical devices, but implantation is associated with a foreign body response (FBR), which may lead to failure of the implants. Surface properties are related to FBR severity. In this review, we zoom in on the cross talk between the two key players, macrophages and fibroblasts, and propose the use of Adverse Outcome Pathways to decipher the causal link between material properties and the severity of the FBR. This approach will help increase a mechanistic understanding of the FBR and, thus, aid in the design of immunomodulatory implant surfaces.

Regenerative medicine aims to restore the function of diseased or damaged tissues and organs by cell therapy, gene therapy, and tissue engineering, along with the adjunctive application of bioactive molecules. Traditional bioactive molecules, such as growth factors and cytokines, have shown great potential in the regulation of cellular and tissue behavior, but have the disadvantages of limited source, high cost, short half-life, and side effects. In recent years, herbal compounds extracted from natural plants/herbs have gained increasing attention. This is not only because herbal compounds are easily obtained, inexpensive, mostly safe, and reliable, but also owing to their excellent effects, including anti-inflammatory, antibacterial, antioxidative, proangiogenic behavior and ability to promote stem cell differentiation. Such effects also play important roles in the processes related to tissue regeneration. Furthermore, the moieties of the herbal compounds can form physical or chemical bonds with the scaffolds, which contributes to improved mechanical strength and stability of the scaffolds. Thus, the incorporation of herbal compounds as bioactive molecules in biomaterials is a promising direction for future regenerative medicine applications. Herein, an overview on the use of bioactive herbal compounds combined with different biomaterial scaffolds for regenerative medicine application is presented. We first introduce the classification, structures, and properties of different herbal bioactive components and then provide a comprehensive survey on the use of bioactive herbal compounds to engineer scaffolds for tissue repair/regeneration of skin, cartilage, bone, neural, and heart tissues. Finally, we highlight the challenges and prospects for the future development of herbal scaffolds toward clinical translation. Overall, it is believed that the combination of bioactive herbal compounds with biomaterials could be a promising perspective for the next generation of regenerative medicine. Impact statement This article reviews the combination of bioactive herbal compounds with biomaterials in the promotion of skin, cartilage, bone, neural, and heart regeneration, due to the anti-inflammatory, antibacterial, antioxidative, and proangiogenic effects of the herbal compounds, but also their effects on the improvement of mechanic strength and stability of biomaterial scaffolds. This review provides a promising direction for the next generation of tissue engineering and regenerative medicine.