Tissue Engineering. Part B, Reviews最新文献

Vascular surgery faces a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency particularly applies to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs holds great promise as a solution to organ shortage for transplantation. To achieve this, it is imperative to (re-)construct a biocompatible and non-thrombogenic vascular network within these organs. In this systematic review, we identify, classify and discuss basic principles and methods used to perform in vitro/ex vivo dynamic thrombogenicity testing of perfusable tissue engineered organs and tissues. We conducted a pre-registered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines, comprising a systematic data extraction, in-depth analysis and risk of bias assessment of 116 included studies. We identified shaking (n=28), flow loop (n=17), ex vivo (arterio-venous shunt, n=33) and dynamic in vitro models (n=38) as main approaches for thrombogenicity assessment. This comprehensive review unveils a prevalent lack of standardization and serves as a valuable guide in the design of standardized experimental setups.

The dura mater, the furthest and strongest layer of the meninges, is crucial for protecting the brain and spinal cord. Its biomechanical behavior is vital, as any alterations can compromise biological functions. In recent decades, interest in the dura mater has increased due to the need for hermetic closure of dural defects prompting the development of several substitutes. Collagen-based dural substitutes are common commercial options, but they lack the complex biological and structural elements of the native dura mater, impacting regeneration and potentially causing complications like wound/postoperative infection and cerebrospinal fluid (CSF) leakage. To face this issue, recent tissue engineering approaches focus on creating biomimetic dura mater substitutes. The objective of this review is to discuss whether mimicking the mechanical properties of native tissue or ensuring high biocompatibility and bioactivity is more critical in developing effective dural substitutes, or if both aspects should be systematically linked. After a brief description of the properties and architecture of the native cranial dura, we describe the advantages and limitations of biomimetic dura mater substitutes to better understand their relevance. In particular, we consider biomechanical properties' impact on dura repair's effectiveness. Finally, the obstacles and perspectives for developing the ideal dural substitute are explored.

Peripheral nerve regeneration after trauma poses a substantial clinical challenge that has already been investigated for many years. Infiltration of immune cells is a critical step in the response to nerve damage that creates a supportive microenvironment for regeneration. In this work, we focus on a special type of immune cell, macrophage, in addressing the problem of neuronal regeneration. We discuss the complex endogenous mechanisms of peripheral nerve injury and regrowth vis-à-vis macrophages, including their recruitment, polarization, and interplay with Schwann cells post-trauma. Furthermore, we elucidate the underlying mechanisms by which exogenous stimuli govern the above events. Finally, we summarize the necessary roles of macrophages in peripheral nerve lesions and reconstruction. There are many challenges in controlling macrophage functions to achieve complete neuronal regeneration, even though considerable progress has been made in understanding the connection between these cells and peripheral nerve damage.

Developing an in vitro model of gingival connective tissue that mimics the original structure and composition of gingiva for clinical grafting is relevant for personalized treatment of missing gingiva. Using tissue engineering techniques allows bypassing limitations encountered with existing solutions to increase oral soft tissue volume. This review aims to systematically analyze the different currently existing cellularized materials and technologies used to engineer gingival substitutes for in vivo applications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. An electronic search on PubMed, Scopus, Web of Science, and Cochrane Library databases was conducted to identify suitable studies. In vivo studies about gingival substitutes and grafts containing oral cells compared with a control to investigate the graft remodeling were included. Risk of bias in the included studies was assessed using the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) 10-item checklist. Out of 631 screened studies, 19 were included. Animal models were mostly rodents, and the most used implantation was subcutaneous. According to the SYRCLE tool, low-to-unclear risk of bias was prevalent. Studies checked vascularization and extracellular remodeling up to 60 days after implantation of the cellularized biomaterial. Cells used were mostly fibroblasts and stem cells from oral origin. Grafts presenting vascularization potential after implantation were produced by tissue engineering technologies including cell seeding or embedding for 14, cell sheets for 2, microsphere for 1, and extrusion 3D bioprinting for 2. Components used to build the scaffold containing the cells are all naturally derived and are mainly fibrin, gelatin, collagen, agarose, alginate, fibroin, guar gum, hyaluronic acid, and decellularized extracellular matrix. The most recurring crosslinking method was using chemicals. All studies except one reported vascularization of the graft after implantation, and some detailed extracellular matrix remodeling. Current solutions are not efficient enough. By assessing the relevant studies on the subject, this systematic review showed that a diversity of cellularized biomaterials substituting gingival connective tissue enables vascularization and extracellular remodeling. Taking the results of this review into account could help improve current bio-inks used in 3D bioprinting for in vivo applications compensating for gingival loss.

Autologous fat grafting is a common procedure in plastic, reconstructive, and aesthetic surgery. However, it is frequently associated with an unpredictable resorption rate of the graft depending on the engraftment kinetics. This, in turn, is determined by the interaction of the grafted adipose tissue with the tissue at the recipient site. Accordingly, preconditioning strategies have been developed following the principle of exposing these tissues in the pretransplantation phase to stimuli inducing endogenous protective and regenerative cellular adaptations, such as the upregulation of stress-response genes or the release of cytokines and growth factors. As summarized in the present review, these stimuli include hypoxia, dietary restriction, local mechanical stress, heat, and exposure to fractional carbon dioxide laser. Preclinical studies show that they promote cell viability, adipogenesis, and angiogenesis, while reducing inflammation, fibrosis, and cyst formation, resulting in a higher survival rate and quality of fat grafts in different experimental settings. Hence, preconditioning represents a promising approach to improve the outcome of fat grafting in future clinical practice. For this purpose, it is necessary to establish standardized preconditioning protocols for specific clinical applications that are efficient, safe, and easy to implement into routine procedures.

Ischemic vascular diseases remain leading causes of disability and death. Although various clinical therapies have been tried, reperfusion injury is a major issue, occurring when blood recirculates at the damaged lesion. As an alternative approach, cell-based therapy has emerged. Mesenchymal stem cells (MSCs) are attractive cellular candidates due to their therapeutic capacities, including differentiation, safety, angiogenesis, and tissue repair. However, low levels of receptors/ligands limit targeted migration of stem cells. Thus, it is important to improve homing efficacy of transplanted MSCs toward damaged endothelium. Among various MSC modulations, ex vivo cell surface engineering could effectively augment homing efficiency by decorating MSC surfaces with alternative receptors/ligands, thereby facilitating intercellular interactions with the endothelium. Especially, exogenous decoration of peptides onto stem cell surfaces could provide appropriate functional signaling moieties to achieve sufficient MSC homing. Based on their protein-like functionalities, high modularity in molecular design, and high specific affinities and multivalency to target receptors, peptides could be representative surface-presentable moieties. Moreover, peptides feature a mild synthetic process, enabling precise control of amino acid composition and sequence. Such ex vivo stem cell surface engineering could be achieved primarily by hydrophobic interactions of the cellular bilayer with peptide-conjugated anchor modules and by covalent conjugation between peptides and available compartments in membranes. To this end, this review provides an overview of currently available peptide-mediated, ex vivo stem cell surface engineering strategies for enhancing MSC homing efficiency by facilitating interactions with endothelial cells. Stem cell surface engineering techniques using peptide-based bioconjugates have the potential to revolutionize current vascular disease treatments while addressing their technical limitations.

The use of biomaterials in the treatment of skin wounds has been steadily increasing over the last two decades. The key to the successful application of biomaterials in scar reduction is the up-to-date knowledge of the actors involved in accelerated healing and the cellular factors that can be implemented in bioinspired materials. Natural models of scarless healing such as oral mucosa, fetal skin and the skin of amphibians, fish, and reptiles are a great source of information. By investigating their microenvironments, cellular factors, and inflammatory self-regulatory systems, a general model of scarless healing can be defined. This review introduces the basic and current concepts of skin wound healing and focuses on providing a detailed overview of the main processes of accelerated healing without scarring. The article outlines the common features and key points that develop and promote scar-free healing. The tissues and healing processes of the selected natural models are described individually (tissue organization, structural components, ratios of cellular factors such as Collagen and transforming growth factor and their mechanisms of regulation of inflammation and scar overgrowth). A comparative work of each natural model concerning healing in human skin is included in the discussion. Finally, the patterns identified through the analysis of each model and their differences from normal healing are presented to facilitate the knowledge for the implementation of new treatments.

Impact statement This review discusses the research done using marine collagens (MCs) on biomaterials for bone, cartilage, and osteochondral tissue regenerative applications with the underlying technologies that enable their development, and explains the methodologies used to characterize MCs highlighting their importance, namely regarding the performance of derived biomaterials, and the inherent properties of such collagens. In the second part, the applicability of MCs as biomaterials for hard tissue applications was studied, focusing on the mostly applied fabrication techniques. In conclusion, this review describes the major challenges to be overcome and the forecast for the upcoming years concerning the use of MCs.

Extensive bone fractures, which can seriously impact both health and quality of life, cannot easily heal naturally, especially if the patient has an underlying medical condition or is aging. The most promising approach to addressing such fractures is bone regeneration through bone tissue engineering. Bone regeneration is a complex process that consists of three distinct phases: inflammation, repair, and remodeling. Macrophages play a bridging role between the various cells involved in each stage of bone regeneration, interacting with different microenvironments and advancing the bone healing process. Although the origin and function of macrophages have been extensively studied, the mechanisms underlying their interaction with the bone healing microenvironment remain unexplored, including the association of microenvironmental changes with macrophage reprogramming and the role of macrophages in cells in the microenvironment. This review summarizes the bone regeneration process and recent advances in research on interactions between macrophages and the bone healing microenvironment and discusses novel biological strategies to promote bone regeneration by modulating macrophages for the treatment of bone injury and loss.

Having genetically related offspring remains an unattainable dream for couples with reproductive failure. Mesenchymal stem cells (MSCs) are multipotent stromal cells derived from various human tissues and organs. As critical paracrine effectors of MSCs, extracellular vesicles (EVs) can carry and deliver bioactive content, thereby participating in intercellular communication and determining cell fate. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown promising therapeutic effects, including repairing injured endometria, restoration of ovarian functions, and improving sperm quantity, morphology, and motility, owing to their regenerative potential, abundant sources, high proliferation rates, low immunogenicity, and lack of ethical issues. However, limited knowledge on purification and isolation of MSC-EVs, therapeutic effects, and unpredictable safety have caused challenges in overcoming female and male infertility. To overcome them, future studies should focus on modification/engineering of MSC-EVs with therapeutic biomolecules and combining attractive biomaterials and MSC-EVs. This review highlights the latest studies on MSC-EVs therapies in infertility and the major challenges that must be overcome before clinical translation.