Tissue and organ dysfunction are major causes of worldwide morbidity and mortality with all medical specialties being impacted. Tissue engineering is an interdisciplinary field relying on the combination of scaffolds, cells, and biologically active molecules to restore form and function. However, clinical translation is still largely hampered by limitations in vascularization. Consequently, a thorough understanding of the microvasculature is warranted. This review provides an overview of (1) angiogenesis, including sprouting angiogenesis, intussusceptive angiogenesis, vascular remodeling, vascular co-option, and inosculation; (2) strategies for vascularized engineered tissue fabrication such as scaffold modulation, prevascularization, growth factor utilization, and cell-based approaches; (3) guided microvascular development via scaffold modulation with electromechanical cues, 3D bioprinting, and electrospinning; (4) surgical approaches to bridge the micro- and macrovasculatures in order to hasten perfusion; and (5) building specific vasculature in the context of tissue repair and organ transplantation, including skin, adipose, bone, liver, kidney, and lung. Our goal is to provide the reader with a translational overview that spans developmental biology, tissue engineering, and clinical surgery.

Human decellularized adipose matrix (hDAM) has emerged as a promising, off-the-shelf option for soft tissue augmentation, providing a biocompatible scaffold that supports angiogenesis, adipogenesis, and volume retention with minimal immunogenicity. This systematic review synthesizes preclinical and clinical evidence on hDAM's regenerative potential, focusing on its capacity to integrate with host tissue and enhance volume retention. A comprehensive literature search was performed across multiple databases yielding 21 studies (14 preclinical, 6 clinical, and 1 combined) that met eligibility criteria. Risk of bias (RoB) was evaluated for animal and human studies using the Collaboration for the Assessment of Risks and Benefits of Anticancer Therapies (CAMARADES) and RoB In Nonrandomized Studies of Interventions (ROBINS-I) tools, respectively. Key preclinical findings indicate that hDAM supports progressive angiogenesis and adipogenesis, with significant weekly increases in vessel formation and adipocyte development. Linear mixed models were used to quantify these rates, showing an increase of 0.366% per week ( < 0.001) in the percentage of CD31+ positive area, and a 3.88% rise in perilipin-positive area per week ( < 0.001), representing angiogenesis and adipogenesis, respectively. Variability in regeneration rates underscores the influence of different hDAM preparation methods, such as enzyme-free decellularization and ultrasonication, which have been shown to improve cell compatibility and volume retention. Clinical studies demonstrate that hDAM achieves notable volume retention and patient satisfaction, particularly in facial and body contouring applications, while also improving skin texture, tone, and functionality. Compared with traditional autologous fat transfer and synthetic fillers, hDAM offers advantages in integration, resorption rates, and low complication risks, without donor site morbidity. Limitations of current studies include variability in hDAM preparation techniques, inconsistent outcome measures, and a paucity of long-term follow-up data. This review establishes hDAM as a safe and effective scaffold for soft tissue regeneration and provides a quantitative analysis of its regenerative timeline. Standardizing preparation methods and outcome measures, coupled with more randomized clinical trials, will be essential for optimizing treatment protocols. Future directions include exploring patient-specific factors and combination therapies to enhance hDAM's applicability in reconstructive and aesthetic surgery.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool in stem cell-based therapy due to their immunomodulatory or regenerative characteristics. Nowadays, controlled application of nonpathogenic bacterial cells and their derivatives has shown promise in preconditioning and manipulating MSC behavior. This approach is being explored in various fields, including immunotherapy, tissue engineering, and cell therapy. However, recent discoveries have elucidated the complex interactions between MSCs and microorganisms, especially bacteria and viruses, raising concerns regarding the utility of MSCs in clinical applications. In this review, we discussed the interactions between MSCs and microorganisms and highlighted both positive and negative aspects. We also examined the use of bacterial-derived compounds in MSCs-mediated interventions. The balanced colonization of the microbiome in organs, such as the oral cavity, not only does not hinder therapeutic interventions but also could be crucial for achieving desirable outcomes. On the contrary, disturbances in the microbiome have been found to disturb the biological potential of MSCs, such as migration, osteogenic differentiation, and cell proliferation. Evidence also suggests that commensal bacteria, following certain interventions, can transition to a pathogenic state when interacting with MSCs, leading to acute inflammation. Indeed, the maintenance of homeostasis through various approaches, such as probiotic application, results in an optimal equilibrium during MSCs-based therapies. However, further investigation into this matter is imperative to identify efficacious interventions.

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.

The increasing number of elderly people across the globe has led to a rise in osteoporosis and bone fractures, significantly impacting the quality of life and posing substantial health and economic burdens. Despite the development of tissue-engineered bone constructs and stem cell-based therapies to address these challenges, their efficacy is compromised by inadequate vascularization and innervation during bone repair. Innervation plays a pivotal role in tissue regeneration, including bone repair, and various techniques have been developed to fabricate innervated bone scaffolds for clinical use. Incorporating neural-related cells and delivering neurotrophic factors are emerging strategies to accelerate bone regeneration through innervation. However, research into neurogenic cell sources remains limited. Meanwhile, neural stem/progenitor cells (NSPCs) are emerging as promising cells for treating neurodegenerative disorders and spinal cord injuries due to their multifunctional capacity in promoting angiogenesis, neurogenesis, and immunomodulation, making them promising candidates for achieving innervation in bone substitutes. In this review, we discuss the regenerative potential of NSPCs in tissue regeneration. We propose their feasibility for bone therapy through their secreted exosomes during traumatic brain injury, contributing to the acceleration of bone healing. Additionally, we discuss the essential neurotrophic factors released from NSPCs and their osteogenic properties. This review emphasizes the necessity for further investigation of the role of NSPCs in bone regeneration.

Osteoporosis, affecting the entire skeletal system, can cause bone mass to diminish, thereby reducing bone strength and elevating fracture risk. Fracture nonunion and bone defects are common in patients with fractures, and pain and loss of function may cause serious distress. The search for a new therapeutic strategy is essential because of the limited therapeutic options available. Bone marrow mesenchymal stem cells (BMSCs) are crucial for bone metabolism and development due to their high self-renewal capabilities. Wnt signaling is a key pathway that plays a significant role in bone formation by regulating the differentiation of BMSCs. Therefore, the osteogenic differentiation of BMSCs can be regulated by activating Wnt signaling as an idea for bone tissue repair. In this review, we systematically compile and analyze the roles of various drugs, biomolecules, exosomes, and biomaterials in influencing the Wnt/β-catenin signaling pathway during the osteogenic differentiation of BMSCs. It is also discussed how these factors impact on BMSCs and the Wnt/β-catenin pathway. Finally, we also present recent advances in combining bone regeneration materials through these factors, which will help subsequent clinical treatment and translation.

Cartilage tissue engineering (CTE) has revolutionized the field of regenerative medicine, offering significant advancements in surgeries such as autologous chondrocyte transplantation. However, despite these advancements, infections associated with cartilage implants remain a persistent challenge, compromising the success of surgeries and patient recovery. To address these challenges, this review provides a comprehensive foundation for researchers interested in addressing infections in CTE. It begins by briefly outlining the major scaffolds currently used in CTE and distinguishing those with antimicrobial properties. Among the antimicrobial scaffolds identified, chitosan and chondroitin sulfate stand out for their promising compatibility and antibacterial properties. The review then explores additives that meet three essential criteria: compatibility with chondrocytes, suitability for use in CTE scaffolds, and antibacterial efficacy. Chitosan, zinc oxide, silver, and copper emerge as leading candidates due to their compatibility with chondrocytes and proven antibacterial capabilities. Importantly, the criteria used in this review were chosen to provide researchers with a practical and reliable starting point for immediate application. However, it is acknowledged that other promising antibacterial modifications such as fabrication processes and additives such as bioactive glass and graphene oxide, which may not fit these criteria, also hold potential for future research and innovation. This review underscores the need for further research and development to enhance infection control measures and improve patient outcomes.

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.

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.

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.

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 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 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.

In the realm of dental tissue regeneration research, various constraints exist such as the potential variance in cell quality, potency arising from differences in donor tissue and tissue microenvironment, the difficulties associated with sustaining long-term and large-scale cell expansion while preserving stemness and therapeutic attributes, as well as the need for extensive investigation into the enduring safety and effectiveness in clinical settings. The adoption of artificial intelligence (AI) technologies has been suggested as a means to tackle these challenges. This is because, tissue regeneration research could be advanced through the use of diagnostic systems that incorporate mining methods such as neural networks (NN), fuzzy, predictive modeling, genetic algorithms, machine learning (ML), cluster analysis, and decision trees. This article seeks to offer foundational insights into a subset of AI referred to as artificial neural networks (ANNs) and assess their potential applications as essential decision-making support tools in the field of dentistry, with a particular focus on tissue engineering research. Although ANNs may initially appear complex and resource intensive, they have proven to be effective in laboratory and therapeutic settings. This expert system can be trained using clinical data alone, enabling their deployment in situations where rule-based decision-making is impractical. As ANNs progress further, it is likely to play a significant role in revolutionizing dental tissue regeneration research, providing promising results in streamlining dental procedures and improving patient outcomes in the clinical setting.

Autologous fat grafting has been widely adopted in cosmetic and reconstructive procedures recently. With the emerging of negative-pressure-assisted liposuction system, the harvesting process of fat grafting is more standardized, controllable, and efficient. Each component in the system could influence the biomechanical environment of lipoaspirate. Several reviews have studied the impact of negative pressure on fat regeneration. As the initial part of the harvesting system, cannulas possess their unique mechanical parameters and their influence on lipoaspirate biomechanical characters, biological behaviors, and regeneration patterns remains unclear. Basic and studies have been performed to determine the possible mechanisms. Instant studies focus on adipocytes, stromal vascular fraction cells, fat particles, and growth factors, while grafting experiments analyze the graft retention rate and histology. Understanding the different regeneration patterns of lipoaspirate and the mechanisms behind may facilitate the choice of harvesting cannulas in clinical practice.

Cartilage plays an important role in supporting soft tissues, reducing joint friction, and distributing pressure. However, its self-repair capacity is limited due to the lack of blood vessels, nerves, and lymphatic systems. Tissue engineering offers a potential solution to promote cartilage regeneration by combining scaffolds, seed cells, and growth factors. Among these, growth factors play a critical role in regulating cell proliferation, differentiation, and extracellular matrix remodeling. However, their instability, susceptibility to degradation and potential side effects limit their effectiveness. This article reviews the main growth factors used in cartilage tissue engineering and their delivery strategies, including affinity-based delivery, carrier-assisted delivery, stimuli-responsive delivery, spatial structure-based delivery, and cell system-based delivery. Each method shows unique advantages in enhancing the delivery efficiency and specificity of growth factors but also faces challenges such as cost, biocompatibility, and safety. Future research needs to further optimize these strategies to achieve more efficient, safe, and economical delivery of growth factors, thereby advancing the clinical application of cartilage tissue engineering.

Three-dimensional (3D) tissue-engineered models are under investigation to recapitulate tissue architecture and functionality, thereby overcoming limitations of traditional two-dimensional cultures and preclinical animal models. This review highlights recent developments in 3D platforms designed to model diseases that affect numerous tissues and organs, including cardiovascular, gastrointestinal, bone marrow, neural, reproductive, and pulmonary systems. We discuss current technologies for engineered tissue models, highlighting the advantages, limitations, and important considerations for modeling tissues and diseases. Lastly, we discuss future advancements necessary to enhance the reliability of 3D models of tissue development and disease.

Articular cartilage is crucial in human physiology, and its degeneration poses a significant public health challenge. While recent advancements in 3D bioprinting and tissue engineering show promise for cartilage regeneration, there remains a gap between research findings and clinical application. This review critically examines the mechanical and biological properties of hyaline cartilage, along with current 3D manufacturing methods and analysis techniques. Moreover, we provide a quantitative synthesis of bioink properties used in cartilage tissue engineering. After screening 181 initial works, 33 studies using extrusion bioprinting were analyzed and synthesized, presenting results that indicate the main materials, cells, and methods utilized for mechanical and biological evaluation. Altogether, this review motivates the standardization of mechanical analyses and biomaterial assessments of 3D bioprinted constructs to clarify their chondrogenic potential.

Amniotic membrane transplantation is commonly employed in ophthalmology to mend corneal epithelial and stromal defects. Its effectiveness in restoring the ocular surface has been widely acknowledged in clinical practice. Nevertheless, there is ongoing debate regarding the comparative effectiveness of using fresh amniotic membranes versus preserved ones. The objective of this meta-analysis was to ascertain whether there is a disparity in the effectiveness of fresh versus preserved amniotic membrane in the restoration of the ocular surface in clinical practice. The study utilized the following keywords: "fresh amniotic membrane," "preserved amniotic membrane," "amniotic membrane transplantation," and "ocular surface reconstruction." The study conducted a comprehensive search for relevant studies published until April 18, 2024. Seven different databases, namely PubMed, Web of Science, Embase, Cochrane, China Knowledge, China Science and Technology Journal VIP database, and Wanfang database, were utilized. The search was performed using the keywords "fresh amniotic membrane," "preserved amniotic membrane," "amniotic membrane transplantation," and "ocular surface reconstruction." The process of literature review and data extraction was carried out separately by two researchers, and all statistical analyses were conducted using Review Manager 5.4.1. The final analysis comprised nine cohort studies, encompassing a total of 408 participants. The statistics included six outcome indicators: visual acuity (relative risk [RR] = 1.07, 95% confidence interval [CI] = 0.93-1.24, = 0); amniotic membrane viability (RR = 1.00, 95% CI = 0.93-1.08, = 0); ocular congestion resolution (RR = 1.11, 95% CI = 0.97-1.26, = 0); fluorescent staining of amniotic membranes on the second day after the operation (RR = 1.31, 95% CI = 0.80-2.14, = 11); postoperative recurrence rate (RR = 1.01, 95% CI = 0.50-2.03, = 0); and premature lysis of amniotic membrane implants (RR = 0.96, 95% CI = 0.49-1.88, = 0). The findings indicated that there was no statistically significant disparity between fresh and preserved amniotic membranes across any of the measured variables. There is no substantial disparity in the effectiveness of fresh and preserved amniotic membrane transplants in restoring the ocular surface, and both yield favorable and consistent outcomes.

Articular cartilage is crucial in human physiology, and its degeneration poses a significant public health challenge. While recent advancements in 3D bioprinting and tissue engineering show promise for cartilage regeneration, there remains a gap between research findings and clinical application. This review critically examines the mechanical and biological properties of hyaline cartilage, along with current 3D manufacturing methods and analysis techniques. Moreover, we provide a quantitative synthesis of bioink properties used in cartilage tissue engineering. After screening 181 initial works, 33 studies using extrusion bioprinting were analyzed and synthesized, presenting results that indicate the main materials, cells, and methods utilized for mechanical and biological evaluation. Altogether, this review motivates the standardization of mechanical analyses and biomaterial assessments of 3D bioprinted constructs to clarify their chondrogenic potential.