Bone regeneration remains a significant clinical challenge in conditions such as trauma, osteoporosis, and aging-related bone loss. Recent advances have highlighted the crucial role of extracellular vesicles, especially exosomes, in intercellular signaling pathways that support bone homeostasis and repair. Among their bioactive cargoes, exosomal RNAs—particularly messenger RNAs and microRNAs—have emerged as central regulators of osteogenesis by modulating gene expression, cellular differentiation, and communication within the bone microenvironment. In this review, we provide a comprehensive summary of exosome biology, including their biogenesis, secretion, uptake mechanisms, and RNA cargo characteristics. We critically examine current evidence on how exosomal RNAs influence the molecular mechanisms of bone formation, remodeling, and regeneration under both physiological and pathological conditions such as fractures, diabetes, osteoporosis, and osteoarthritis. Furthermore, we discuss the emerging therapeutic potential of engineered exosomes as RNA delivery systems in bone tissue engineering and regenerative medicine. A better understanding of the functional roles and clinical relevance of exosomal RNAs may pave the way for next-generation, RNA-based therapies in skeletal repair and treatment of bone-related diseases. Impact Statement This review highlights the crucial role of exosomal mRNAs and microRNAs in regulating osteogenesis and bone regeneration. By elucidating the molecular mechanisms and signaling pathways involved, it provides new insights into the potential of exosome-based therapies in bone tissue engineering. This work may accelerate the development of innovative RNA-based regenerative strategies, ultimately improving treatment outcomes for bone diseases and injuries.

The craniofacial region contains skin, bones, cartilage, the temporomandibular joint (TMJ), teeth, periodontal tissues, mucosa, salivary glands, muscles, nerves, and blood vessels. Applying tissue engineering therapeutically helps replace lost tissues after trauma or cancer. Despite recent advances, it remains essential to standardize and validate the most appropriate animal models to effectively translate preclinical data to clinical situations. Therefore, this review focused on applying various animal models in craniofacial tissue engineering and regeneration. This research was based on PubMed, Scopus, and Google Scholar data available until January 2023. This study included only English-language publications describing animal models' application in craniofacial tissue engineering (in vivo and review studies). Study selection was based on evaluating titles, abstracts, and full texts. The total number of initial studies was 6454. Following the screening process, 295 articles remained on the final list. Numerous in vivo studies have shown that small and large animal models can benefit clinical conditions by assessing the efficacy and safety of new therapeutic interventions, devices, and biomaterials in animals with similar diseases/defects to humans. Different species' anatomical, physiologic, and biological features must be considered in developing innovative, reproducible, and discriminative experimental models to select an appropriate animal model for a specific tissue defect. As a result, understanding the parallels between human and veterinary medicine can benefit both fields.

Dentin is a bone-like matrix that forms the bulk of the tooth. By fabricating dentin with protocols involving demineralization, sterilization, and preservation, treated dentin matrix (TDM)/demineralized dentin matrix (DDM) could be obtained, which is considered as a useful tool for bone and tooth-tissue regeneration. Non-negligible inflammatory and immune responses are reviewed in this article of autogenous, allogeneic, and xenogeneic TDM/DDM for the first time. Both autogenous and allogeneic TDM/DDM showed good biocompatibility in original and clinical studies, while a few cases reported the observation of inflammatory cells around tissue samples. As for xenogeneic TDM/DDM, multiple immune responses were revealed. Immune cells, including eosinocytes, macrophages, lymphocytes, mutinucleated giant cell, M1/M2 macrophages, and Th1-type CTL responses were involved. To avoid these adverse inflammatory responses caused by TDM/DDM implantation, some of the effective fabricating methods are discussed to reduce host immune responses to TDM/DDM.

Three-dimensional (3D) bioprinting, or additive manufacturing, is a rapid fabrication technique with the foremost objective of creating biomimetic tissue and organ replacements in hopes of restoring normal tissue function and structure. Generating the engineered organs with an infrastructure that is similar to that of the real organs can be beneficial to simulate the functional organs that work inside our bodies. Photopolymerization-based 3D bioprinting, or photocuring, has emerged as a promising method in engineering biomimetic tissues due to its simplicity, and noninvasive and spatially controllable approach. In this review, we investigated types of 3D printers, mainstream materials, photoinitiators, phototoxicity, and selected tissue engineering applications of 3D photopolymerization bioprinting.

Adipose tissue resorption after fat grafting is a major drawback in plastic and reconstructive surgery, which is primarily caused by the insufficient blood perfusion of the grafts in the initial phase after transplantation. To overcome this problem, several promising strategies to boost the vascularization and, thus, increase survival rates of fat grafts have been developed in preclinical studies in recent years. These include the angiogenic stimulation of the grafts by growth factors and botulinum neurotoxin A, biologically active gels, and cellular enrichment, as well as the physical and pharmacological stimulation of the transplantation site. To transfer these approaches into future clinical practice, it will be necessary to establish standardized procedures for their safe application in humans. If this succeeds, the surgical outcomes of fat grafting may be markedly improved, resulting in a significant reduction of the physical and psychological stress for the patients.

Surgical implants are increasingly used across multiple medical disciplines, with applications ranging from tissue reconstruction to improving compromised organ and limb function. Despite their significant potential for improving health and quality of life, biomaterial implant function is severely limited by the body's immune response to its presence: this is known as the foreign body response (FBR) and is characterized by chronic inflammation and fibrotic capsule formation. This response can result in life-threatening sequelae such as implant malfunction, superimposed infection, and associated vessel thrombosis, in addition to soft tissue disfigurement. Patients may require frequent medical visits, as well as repeated invasive procedures, increasing the burden on an already strained health care system. Currently, the FBR and the cells and molecular mechanisms that mediate it are poorly understood. With applications across a wide array of surgical specialties, acellular dermal matrix (ADM) has emerged as a potential solution to the fibrotic reaction seen with FBR. Although the mechanisms by which ADM decreases chronic fibrosis remain to be clearly characterized, animal studies across diverse surgical models point to its biomimetic properties that facilitate decreased periprosthetic inflammation and improved host cell incorporation. Impact Statement Foreign body response (FBR) is a significant limitation to the use of implantable biomaterials. Acellular dermal matrix (ADM) has been observed to decrease the fibrotic reaction seen with FBR, although its mechanistic details are poorly understood. This review is dedicated to summarizing the primary literature on the biology of FBR in the context of ADM use, using surgical models in breast reconstruction, abdominal and chest wall repair, and pelvic reconstruction. This article will provide readers with an overarching review of shared mechanisms for ADM across multiple surgical models and diverse anatomical applications.

The consequences of military conflict, accidents, and diseases have led to the definition-and subsequent study-of the pathological condition now known as volumetric muscle loss (VML). VML is a significant injury to skeletal muscle tissue on a scale that is endogenously irrecoverable and leads to chronic functional deficits and long-term disability. Currently, there lacks a definitive approach to meaningfully restore the tissue and function lost by those afflicted, ushering a need for scientific activities and associated funding to both facilitate a deeper understanding of the pathobiology of VML as well as to develop and assess clinically relevant therapeutics and treatment strategies. Thereby, evaluation of the VML field is crucial to gauging the return on resource expenditures and to understand the evolution of the field to guide future directions. This article presents a bibliometric analysis of publicly available data to explore the growth of the VML field since its genesis and to highlight its prosperity through its expanding literature, its development and evaluation of promising treatment strategies, rising financial investments, and innovation. Altogether, the bibliometric analysis reveals the field of VML as an emergent research focus that is productive and translational. Impact statement Analyses of a research topic are fundamental toward evaluating the returns on investment and appreciating the evolution of the research toward novel directions. This study aims to highlight the growing field of volumetric muscle loss (VML), defined as a significant injury to skeletal muscle tissue that leads to functional impairment and is irrecoverable through inherent regenerative mechanisms. The analysis of bibliometric and publicly available data provides evidence that the field of VML has an expanding research interest and investment, with biomaterials at the forefront of study.

The most common preservation technique for liver grafts is static cold storage. Due to the organ shortage for liver transplantation (LT), extended criteria donor (ECD) allografts are increasingly used-despite the higher risk of inferior outcome after transplantation. Ex vivo liver machine perfusion (MP) has been developed to improve the outcome of transplantation, especially with ECD grafts, and is currently under evaluation in clinical trials. We performed a literature search on PubMed and ISI Web of Science to assemble an overview of rodent and porcine animal models of ex vivo liver MP for transplantation, which is essential for the present and future development of clinical liver MP. Hypothermic, subnormothermic, and normothermic MP systems have been successfully used for rat and pig LT. In comparison with hypothermic systems, normothermic perfusion often incorporates a dialysis unit. Moreover, it enables metabolic assessment of liver grafts. Allografts experiencing warm ischemic time have a superior survival rate after MP compared with cold storage alone, irrespective of the temperature used for perfusion. Furthermore, ex vivo MP improves the outcome of regular and ECD liver grafts in animal models. Small and large animal models of ex vivo liver MP are available to foster the further development of this new technology. Impact Statement Ex vivo machine perfusion is an important part of current research in the field of liver transplantation. While evidence for improve storage is constantly rising, the development of future applications such as quality assessment and therapeutic interventions necessitates robust animal models. This review is intended to provide an overview of this technology in common large and small animal models and to give an outlook on future applications. Moreover, we describe developmental steps that can be followed by others, and which can help to decrease the number of animals used for experiments based on the replace, reduce, refine concept.

Rebuilding the kidney in the context of tissue engineering offers a major challenge as the organ is structurally complex and has a high variety of specific functions. Recreation of kidney function is inherently connected to the formation of tubules since the functional subunit of the kidney, the nephron, is based on tubular structures. In vivo, tubulogenesis culminates in a perfectly shaped, patterned, and functional renal tubule via different morphogenic processes that depend on delicately orchestrated chemical, physical, and mechanical interactions between cells and between cells and their microenvironment. This review summarizes the current understanding of the role of the microenvironment in the morphogenic processes involved in in vivo renal tubulogenesis. We highlight the current state-of-the-art of renal tubular engineering and provide a view on the design elements that can be extracted from these studies. Next, we discuss how computational modeling can aid in specifying and identifying design parameters and provide directions on how these design parameters can be incorporated in biomaterials for the purpose of engineering renal tubulogenesis. Finally, we propose that a step-by-step reciprocal interaction between understanding and engineering is necessary to effectively guide renal tubulogenesis. Impact statement Tubular tissue engineering lies at the foundation of regenerating kidney tissue function, as the functional subunit of the kidney, the nephron, is based on tubular structures. Guiding renal tubulogenesis toward functional renal tubules requires in-depth knowledge of the developmental processes that lead to the formation of native tubules as well as engineering approaches to steer these processes. In this study, we review the role of the microenvironment in the developmental processes that lead to functional renal tubules and give directions how this knowledge can be harnessed for biomaterial-based tubular engineering using computational models.