Impact of Collared Peccaries Dycotiles tajacu (Artiodactyla: Tayassuidae) on understory vegetation in the tropical rainforest of the Nogal-La Selva Biological Corridor, Costa Rica / Impacto del pecarí de collar, Dycotiles tajacu (Artiodactyla: Tayassuidae) en la vegetación del sotobosque del bosque tropical húmedo del Corredor Biológico Local Nogal-La Selva, Costa Rica

Abstract Introduction: Evidence suggests that herbivores, such as peccaries, shape vegetation structure and diversity through predation, trampling, dispersal, and rooting behavior. Objective: To evaluate the impact of peccaries (Dycotiles tajacu) on the understory vegetation of the tropical rainforest in the Nogal-La Selva Local Biological Corridor, Costa Rica, comparing a site with the absence of peccaries to another with the presence of these animals. Methodology: From June to November 2021, 20 experimental exclusions and 20 free access plots, each measuring 2 m2 were used to quantify herbivory, the number of leaf blades, damaged leaves, healthy leaves, sapling height, and fallen biomass at both sites. Results: A higher sapling density was found in the Nogal Reserve, but a lower sapling diversity, while in La Selva there was a higher sapling diversity, but a lower density of seedlings. Herbivory and sapling height in La Selva exceeded those in Nogal. The exclusion of peccaries reduced seedling damage but did not affect the dynamics of fallen biomass. Conclusion: For the design, implementation, and evaluation of the effectiveness of biological corridors, it is crucial to consider plant-animal interactions to enhance the flow of ecological processes through functional and structural connectivity, analyzed from interactions such as those presented in this paper.

Resumen Introducción: Existe evidencia que herbívoros, como los saínos, dan forma a la estructura y diversidad de la vegetación a través del comportamiento de depredación, pisoteo, dispersión y enraizamiento. Objetivo: Evaluar el impacto de los saínos (Dycotiles tajacu) en la vegetación del sotobosque del bosque tropical húmedo en el Corredor Biológico Local Nogal-La Selva, Costa Rica, en un sitio con ausencia y en otro con presencia de saínos. Métodos: De junio a noviembre de 2021 se utilizaron 20 exclusiones experimentales y 20 parcelas de acceso libre de 2 m2, se cuantifico la herbivoría, número de láminas foliares, hojas dañadas, hojas sanas, altura de brinzales y biomasa caída en ambos sitios. Resultados: Se encontró una mayor densidad de brinzales en Reserva Nogal pero una menor diversidad, contrario en La Selva donde se encontró una mayor diversidad de brinzales, pero una menor densidad de plántulas. La herbivoría y la altura de brinzales en La Selva fue mayor que en Nogal. La exclusión de los saínos disminuyó el daño a las plántulas, pero no afectó la dinámica de la biomasa caída. Conclusión: Es necesario contemplar para el diseño, implementación y evaluación de la efectividad de corredores biológicos, las interacciones planta-animal, para potencializar el flujo de procesos ecológicos mediante la conectividad funcional y estructural, analizada a partir de interacciones como las presentadas en este trabajo.

Application of Mesenchymal Stem Cells and Exosome alone or Combination Therapy as a Treatment Strategy for Wound Healing.

The process of wound healing consists of multiple phases, and any disruptions in these phases can lead to the wound becoming chronic and impose heavy financial and psychological costs on the patient and a huge economic burden on the country's healthcare system. Various treatments such as drugs, matrix and scaffolds, blood products, cell therapy, and a combination of these treatments are used for wound healing. The use of mesenchymal stem cells (MSCs) is one of these methods that have produced appropriate responses in the healing of patients' wounds. MSCs by secreting growth factors, cytokines, chemokines, and RNAs elicit changes in cell proliferation, migration, growth, signaling, immunomodulation, and wound re-epithelialization process, and as a result, accelerate wound closure and wound healing. These cells can be isolated from different body sources with different cell characteristics and used directly on the wound site or by injection. In addition, MSCs-derived exosomes have attracted growing attention due to circumventing concerns relating to the direct use of MSCs. To increase the performance of MSCs, they can be used together with other compounds such as platelets, matrices, or scaffolds. This study examined the functions of MSCs in wound healing, as well as the vesicles they secrete, cellular and molecular mechanisms, and combined treatments with MSCs for wound healing.

Unleashing metabolic power for axonal regeneration.

Axon regeneration requires the mobilization of intracellular resources, including proteins, lipids, and nucleotides. After injury, neurons need to adapt their metabolism to meet the biosynthetic demands needed to achieve axonal regeneration. However, the exact contribution of cellular metabolism to this process remains elusive. Insights into the metabolic characteristics of proliferative cells may illuminate similar mechanisms operating in axon regeneration; therefore, unraveling previously unappreciated roles of metabolic adaptation is critical to achieving neuron regrowth, which is connected to the therapeutic strategies for neurological conditions necessitating nerve repairs, such as spinal cord injury and stroke. Here, we outline the metabolic role in axon regeneration and discuss factors enhancing nerve regrowth, highlighting potential novel metabolic treatments for restoring nerve function.

A nanozyme-functionalized bilayer hydrogel scaffold for modulating the inflammatory microenvironment to promote osteochondral regeneration.

BACKGROUND: The incidence of osteochondral defects caused by trauma, arthritis or tumours is increasing annually, but progress has not been made in terms of treatment methods. Due to the heterogeneous structure and biological characteristics of cartilage and subchondral bone, the integration of osteochondral repair is still a challenge. RESULTS: In the present study, a novel bilayer hydrogel scaffold was designed based on anatomical characteristics to imitate superficial cartilage and subchondral bone. The scaffold showed favourable biocompatibility, and the addition of an antioxidant nanozyme (LiMn2O4) promoted reactive oxygen species (ROS) scavenging by upregulating antioxidant proteins. The cartilage layer effectively protects against chondrocyte degradation in the inflammatory microenvironment. Subchondral bionic hydrogel scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) by regulating the AMPK pathway in vitro. Finally, an in vivo rat preclinical osteochondral defect model confirmed that the bilayer hydrogel scaffold efficiently promoted cartilage and subchondral bone regeneration. CONCLUSIONS: In general, our biomimetic hydrogel scaffold with the ability to regulate the inflammatory microenvironment can effectively repair osteochondral defects. This strategy provides a promising method for regenerating tissues with heterogeneous structures and biological characteristics.

Engineering a durable BDDE cross-linked collagen filler for skin rejuvenation.

Skin aging, characterized by reduced regeneration, chronic inflammation, and heightened skin cancer risk, poses a significant challenge. Collagen fillers have emerged as a potential solution for skin rejuvenation by stimulating collagen regeneration. However, their clinical efficacy is limited by inherent instability and vulnerability toin vivodegradation by collagenase. Chemical cross-linking presents a promising approach to enhance stability, but it carries risks such as cytotoxicity, calcification, and discoloration. Here, we introduce a highly durable 1,4-butanediol diglycidyl ether (BDDE) cross-linked collagen filler for skin rejuvenation. BDDE effectively cross-links collagen, resulting in fillers with exceptional mechanical strength and injectability. These fillers demonstrate favorable stability and durability, promoting proliferation, adhesion, and spreading of human foreskin fibroblast-1 cellsin vitro. In vivostudies confirm enhanced collagen regeneration without inducing calcification. BDDE cross-linked collagen fillers offer promising prospects for medical cosmetology and tissue regeneration.

An Outline on the Advancements in Surgical Management of Osteoporosis-Associated Fractures.

Osteoporosis significantly impairs bone density and increases fracture risk, representing a substantial global health challenge. The effectiveness of traditional treatments such as calcium supplementation and exercise in completely preventing fractures is limited. This review explores recent advancements in surgical techniques and treatment modalities to manage osteoporotic fractures better and improve patient outcomes. Osteoporotic fractures demand specialized surgical techniques due to compromised bone quality. Vertebroplasty and kyphoplasty are minimally invasive procedures that provide rapid pain relief and structural support using bone cement. While vertebroplasty is effective, it carries risks of cement leakage and new fractures. Kyphoplasty, with added balloon inflation, reduces leakage risk and improves vertebral height restoration but is costlier. Cement-augmented screws enhance fixation but can increase adjacent fracture risk and pose long-term complications. Surgical advancements encompass robotic-assisted surgery, offering precision and accelerated recovery, alongside biologic agents like bone morphogenetic proteins (BMPs), which enhance bone healing while reducing secondary interventions and eliminating donor site morbidity. Bone graft substitutes such as calcium phosphate cements enhance biomechanical compatibility, decrease morbidity, and reduce fracture loss and pain. Balloon kyphoplasty aids in height restoration and pain relief and diminishes the risk of subsequent vertebral fractures. Bioglass scaffolds promote bone regeneration by improving bone mineral density and lowering the incidence of new fractures. Optimal perioperative care, including patient selection, nutritional management, and early mobilization strategies, is crucial for mitigating risks in vulnerable populations. While current surgical interventions provide significant pain relief and functional benefits, ongoing research and multidisciplinary collaboration are crucial to prospectively refine these techniques and reduce the burden of osteoporosis. New technologies, such as tissue engineering and gene editing, hold potential for future treatment paradigms.

Comparative evaluation of the effectiveness of concentrated growth factor alone and in combination with diode laser application in the treatment of intrabony periodontal defects: A clinical and radiographic split-mouth study.

Background: Applying autologous growth factors and diode laser in periodontal therapy enhances fibroblast-mediated new attachment and osteoblastic differentiation. Hence, this study compared and evaluated the effectiveness of concentrated growth factor (CGF) alone and with diode laser application in managing intrabony periodontal defects. Methods: Ten patients with stage III periodontitis were included in this study. All the patients underwent an open flap debridement (OFD) procedure followed by CGF membrane placement in the intrabony defect in site A, whereas, in site B, after OFD, all the patients underwent diode laser irradiation before CGF membrane placement. Plaque and gingival bleeding index (PI & GBI), PPD, and clinical attachment level (CAL) were evaluated at baseline and 3 and 6 months later. Bone fill (BF), BF%, bone crest changes (BCC), and BCC% were assessed radiographically at six months postoperatively. Results: Significant reductions in PI and GBI scores, probing pocket depth (PPD), and CAL gain were observed at both sites 3 and 6 months from baseline. A significant reduction in PPD and CAL gain was noted between sites, which were higher in site B than in site A with a mean difference of 0.70±0.05 mm and 1.30±0.18 mm, 0.90±1.89 mm at 3 and 6 months, respectively. Radiographic measurement showed better BF, BF%, BCC, and BCC% at both sites at six months, which were higher at site B than at site A but statistically insignificant. Conclusion: The combination of CGF and diode laser application has demonstrated successful and promising results in terms of regeneration, improving the clinical and radiographic parameters.

Supra-Alveolar Bone Regeneration: Progress, Challenges, and Future Perspectives.

Periodontitis is a highly prevalent disease that damages the supporting tissues of a tooth, including the alveolar bone. Alveolar bone loss owing to periodontitis is broadly categorized as supra-alveolar and intra-alveolar bone loss. In intra-alveolar bone loss, the defect has an angular or oblique orientation to the long axis of the tooth in an apical direction. In contrast, the defect is perpendicular to the long axis of the tooth in supra-alveolar bone loss. Unlike intra-alveolar bone defects, supra-alveolar bone defects lack supporting adjacent space, which makes supra-alveolar bone regeneration more challenging. In addition, the limited availability of resources in terms of vascularity and underlying tissues is another obstacle to supra-alveolar bone regeneration. Currently, supra-alveolar bone loss is the least predictable periodontal defect type in regenerative periodontal therapy. In addition, supra-alveolar bone loss is much more common than other alveolar bone loss. Despite its prevalence, research on supra-alveolar bone regeneration remains sparse, indicating an unmet need for significant research efforts in this area. This review summarize recent advances, obstacles, and future directions in the field of supra-alveolar bone regeneration. We discuss the biomaterials, bioactive molecules, and cells that have been tested for supra-alveolar bone regeneration, followed by pre-clinical and clinical approaches employed in this field. Additionally, we highlight obstacles and present future directions that will propel supra-alveolar bone research forward.

Significance and considerations of establishing standardized critical values for critical size defects in animal models of bone tissue regeneration.

Establishing animal models with critical size defects (CSDs) is critical for conducting experimental investigations engineering of bone tissue regeneration. Currently, a standardised protocol for establishing an animal CSDs model has not been developed. Furthermore, a consensus has not been reached regarding the critical values of CSDs. Successful establishment of animal models for CSDs is a complex process that requires researchers to meticulously consider a variety of factors such as age, species, bone defect size and anatomic location. The specific numerical values for CSDs in small animal models vary, and a clear definition of the critical value for large animal CSDs models in the literature is still lacking. This review consolidates the advancements in critical bone defects animal models by outlining the research landscape across variables, including animal species, age groups, bone defect sites, and sizes, to offer valuable guidance and a theoretical framework for the establishment of pertinent experimental animal models.

Inflammation is a critical factor for successful regeneration of the adult zebrafish retina in response to diffuse light lesion.

Inflammation can lead to persistent and irreversible loss of retinal neurons and photoreceptors in mammalian vertebrates. In contrast, in the adult zebrafish brain, acute neural inflammation is both necessary and sufficient to stimulate regeneration of neurons. Here, we report on the critical, positive role of the immune system to support retina regeneration in adult zebrafish. After sterile ablation of photoreceptors by phototoxicity, we find rapid response of immune cells, especially monocytes/microglia and neutrophils, which returns to homeostatic levels within 14 days post lesion. Pharmacological or genetic impairment of the immune system results in a reduced Müller glia stem cell response, seen as decreased reactive proliferation, and a strikingly reduced number of regenerated cells from them, including photoreceptors. Conversely, injection of the immune stimulators flagellin, zymosan, or M-CSF into the vitreous of the eye, leads to a robust proliferation response and the upregulation of regeneration-associated marker genes in Müller glia. Our results suggest that neuroinflammation is a necessary and sufficient driver for retinal regeneration in the adult zebrafish retina.

Novel 3D printed TPMS scaffolds: microstructure, characteristics and applications in bone regeneration.

Bone defect disease seriously endangers human health and affects beauty and function. In the past five years, the three dimension (3D) printed radially graded triply periodic minimal surface (TPMS) porous scaffold has become a new solution for repairing bone defects. This review discusses 3D printing technologies and applications for TPMS scaffolds. To this end, the microstructural effects of 3D printed TPMS scaffolds on bone regeneration were reviewed and the structural characteristics of TPMS, which can promote bone regeneration, were introduced. Finally, the challenges and prospects of using TPMS scaffolds to treat bone defects were presented. This review is expected to stimulate the interest of bone tissue engineers in radially graded TPMS scaffolds and provide a reliable solution for the clinical treatment of personalised bone defects.

Overlooked Impacts of Alcohols in Electro-H2O2 and Fenton Chemistry.

Alcohols are promising fuels for direct alcohol fuel cells and are common scavengers to identify reactive oxygen species (ROS) in electro-Fenton (EF) systems. However, the side impacts of alcohols on oxygen reduction reactions and ROS generation are controversial due to the complex interactions between electrodes and alcohol-containing electrolytes. Herein, we employed synchrotron-Fourier-transform infrared spectroscopy and electron paramagnetic resonance technologies to directly observe the changes of chemical species and electrochemical properties on the electrode surface. Our studies suggested that alcohols exhibited different limiting degrees on proton (H+) mass transfer toward the catalytic surface, following an order of methanol < ethanol < isopropanol < tert-butyl alcohol (TBA). In addition, the formation of hydrophobic TBA clusters at high concentrations (>400 mM) resulted in a significant reduction in ionic conductivity and an elevation in charge transfer resistance, which impedes H+ mass transfer and raises the energy barrier for 2e- oxygen reduction reaction processes. Moreover, the organic radical •CH2(CH3)2CH2OH produced by the interaction of Fe3+ and •OH with the alcohol in the EF system serves as a crucial intermediate in facilitating H2O2 regeneration, which complicates the quenching effect of alcohols on •OH identification. Therefore, it is recommended that methanol should be used as the scavenger instead of TBA and the concentration should be less than 400 mM in EF systems.

Mesenchymal Stromal Cells for the Enhancement of Surgical Flexor Tendon Repair in Animal Models: A Systematic Review and Meta-Analysis.

Flexor tendon lacerations are primarily treated by surgical repair. Limited intrinsic healing ability means the repair site can remain weak. Furthermore, adhesion formation may reduce range of motion post-operatively. Mesenchymal stromal cells (MSCs) have been trialled for repair and regeneration of multiple musculoskeletal structures. Our goal was to determine the efficacy of MSCs in enhancing the biomechanical properties of surgically repaired flexor tendons. A PRISMA systematic review was conducted using four databases (PubMed, Ovid, Web of Science, and CINAHL) to identify studies using MSCs to augment surgical repair of flexor tendon injuries in animals compared to surgical repair alone. Nine studies were included, which investigated either bone marrow- or adipose-derived MSCs. Results of biomechanical testing were extracted and meta-analyses were performed regarding the maximum load, friction and properties relating to viscoelastic behaviour. There was no significant difference in maximum load at final follow-up. However, friction, a surrogate measure of adhesions, was significantly reduced following the application of MSCs (p = 0.04). Other properties showed variable results and dissipation of the therapeutic benefits of MSCs over time. In conclusion, MSCs reduce adhesion formation following tendon injury. This may result from their immunomodulatory function, dampening the inflammatory response. However, this may come at the cost of favourable healing which will restore the tendon's viscoelastic properties. The short duration of some improvements may reflect MSCs' limited survival or poor retention. Further investigation is needed to clarify the effect of MSC therapy and optimise its duration of action.

Alveolar Ridge Preservation Using a Novel Species-Specific Collagen-Enriched Deproteinized Bovine Bone Mineral: Histological Evaluation of a Prospective Case Series.

In recent years, the significance of maintaining the alveolar ridge following tooth extractions has markedly increased. Alveolar ridge preservation (ARP) is a commonly utilized technique and a variety of bone substitute materials and biologics are applied in different combinations. For this purpose, a histological evaluation and the clinical necessity of subsequent guided bone regeneration (GBR) in delayed implantations were investigated in a prospective case series after ARP with a novel deproteinized bovine bone material (95%) in combination with a species-specific collagen (5%) (C-DBBM). Notably, block-form bone substitutes without porcine collagen are limited, and moreover, the availability of histological data on this material remains limited. Ten patients, each scheduled for tooth extraction and desiring future implantation, were included in this study. Following tooth extraction, ARP was performed using a block form of C-DBBM in conjunction with a double-folded bovine cross-linked collagen membrane (xCM). This membrane was openly exposed to the oral cavity and secured using a crisscross suture. After a healing period ranging from 130 to 319 days, guided trephine drilling was performed for implant insertion utilizing static computer-aided implant surgery (s-CAIS). Cores harvested from the area previously treated with ARP were histologically processed and examined. Guided bone regeneration (GBR) was not necessary for any of the implantations. Histological examination revealed the development of a lattice of cancellous bone trabeculae through appositional membranous osteogenesis at various stages surrounding C-DBBM granules as well as larger spongy or compact ossicles with minimal remnants. The clinical follow-up period ranged from 2.5 to 4.5 years, during which no biological or technical complications occurred. Within the limitations of this prospective case series, it can be concluded that ARP using this novel C-DBBM in combination with a bovine xCM could be a treatment option to avoid the need for subsequent GBR in delayed implantations with the opportunity of a bovine species-specific biomaterial chain.

Adipose Tissue Derivatives in Peripheral Nerve Regeneration after Transection: A Systematic Review.

INTRODUCTION: Peripheral nerve injury (PNI) is increasingly prevalent and challenging to treat despite advances in microsurgical techniques. In this context, adipose tissue derivatives, such as adipose-derived stem cells, nanofat, and stromal vascular fraction have been gaining attention as potential allies in peripheral nerve regeneration. OBJECTIVES: This study aims to explore the use of adipose tissue derivatives in nerve regeneration following peripheral nerve transection in murine models. Thus, we assess and synthesize the key techniques and methods used for evaluating the obtained nerve regeneration to guide future experimental research and clinical interventions. METHODOLOGY: A systematic review was conducted in February 2024, adhering to the Cochrane and PRISMA 2020 guidelines, using the PubMed, SciELO, and LILACS databases. The focus was on experimental studies involving adipose tissue derivatives in nerve regeneration in animal models post-transection. Only experimental trials reporting nerve regeneration outcomes were included; studies lacking a comparator group or evaluation methods were excluded. RESULTS: Out of 273 studies initially identified from MEDLINE, 19 were selected for detailed analysis. The average study included 32.5 subjects, with about 10.2 subjects per intervention subgroup. The predominant model was the sciatic nerve injury with a 10 mm gap. The most common intervention involved unprocessed adipose-derived stem cells, utilized in 14 articles. CONCLUSIONS: This review underscores the significant potential of current methodologies in peripheral nerve regeneration, particularly highlighting the use of murine models and thorough evaluation techniques.

Chitosan Scaffolds from Crustacean and Fungal Sources: A Comparative Study for Bone-Tissue-Engineering Applications.

Chitosan (CS), a biopolymer, holds significant potential in bone regeneration due to its biocompatibility and biodegradability attributes. While crustacean-derived CS is conventionally used in research, there is growing interest in fungal-derived CS for its equally potent properties in bone regenerative applications. Here, we investigated the physicochemical and biological characteristics of fungal (MDC) and crustacean (ADC)-derived CS scaffolds embedded with different concentrations of tricalcium phosphate minerals (TCP), i.e., 0(wt)%: ADC/MDC-1, 10(wt)%: ADC/MDC-2, 20(wt)%: ADC/MDC-3 and 30(wt)%: ADC/MDC-4. ADC-1 and MDC-1 lyophilised scaffolds lacking TCP minerals presented the highest zeta potentials of 47.3 ± 1.2 mV and 55.1 ± 1.6 mV, respectively. Scanning electron microscopy revealed prominent distinctions whereby MDC scaffolds exhibited striation-like structural microarchitecture in contrast to the porous morphology exhibited by ADC scaffold types. With regard to the 4-week scaffold mass reductions, MDC-1, MDC-2, MDC-3, and MDC-4 indicated declines of 55.98 ± 4.2%, 40.16 ± 3.6%, 27.05 ± 4.7%, and 19.16 ± 5.3%, respectively. Conversely, ADC-1, ADC-2, ADC-3, and ADC-4 presented mass reductions of 35.78 ± 5.1%, 25.19 ± 4.2%, 20.23 ± 6.3%, and 13.68 ± 5.4%, respectively. The biological performance of the scaffolds was assessed through in vitro bone marrow mesenchymal stromal cell (BMMSCs) attachment via indirect and direct cytotoxicity studies, where all scaffold types presented no cytotoxic behaviours. MDC scaffolds indicated results comparable to ADC, where both CS types exhibited similar physiochemical properties. Our data suggest that MDC scaffolds could be a potent alternative to ADC-derived scaffolds for bone regeneration applications, particularly for 10(wt)% TCP concentrations.

Fabrication and Evaluation of PCL/PLGA/ß-TCP Spiral-Structured Scaffolds for Bone Tissue Engineering.

Natural bone is a complex material that has been carefully designed. To prepare a successful bone substitute, two challenging conditions need to be met: biocompatible and bioactive materials for cell proliferation and differentiation, and appropriate mechanical stability after implantation. Therefore, a hybrid Poly ε-caprolactone/Poly(lactic-co-glycolide)/ß-tricalcium phosphate (PCL/PLGA/ß-TCP) scaffold has been introduced as a suitable composition that satisfies the above two conditions. The blended PCL and PLGA can improve the scaffold's mechanical properties and biocompatibility compared to single PCL or PLGA scaffolds. In addition, the incorporated ß-TCP increases the mechanical strength and osteogenic potential of PCL/PLGA scaffolds, while the polymer improves the mechanical stability of ceramic scaffolds. The PCL/PLGA/ß-TCP scaffold is designed using spiral structures to provide a much better transport system through the gaps between spiral walls than conventional cylindrical scaffolds. Human fetal osteoblasts (hFOBs) were cultured on spiral PCL/PLGA/ß-TCP (PPBS), cylindrical PCL/PLGA/ß-TCP (PPBC), and cylindrical PCL scaffolds for a total of 28 days. The cell proliferation, viability, and osteogenic differentiation capabilities were analyzed. Compared with PCL and PPBC scaffolds, the PPBS scaffold exhibits great biocompatibility and potential to stimulate cell proliferation and differentiation and, therefore, can serve as a bone substitute for bone tissue regeneration.

Anti-Ferroptotic Treatment Deteriorates Myocardial Infarction by Inhibiting Angiogenesis and Altering Immune Response.

Mammalian cardiomyocytes have limited regenerative ability. Cardiac disease, such as congenital heart disease and myocardial infarction, causes an initial loss of cardiomyocytes through regulated cell death (RCD). Understanding the mechanisms that govern RCD in the injured myocardium is crucial for developing therapeutics to promote heart regeneration. We previously reported that ferroptosis, a non-apoptotic and iron-dependent form of RCD, is the main contributor to cardiomyocyte death in the injured heart. To investigate the mechanisms underlying the preference for ferroptosis in cardiomyocytes, we examined the effects of anti-ferroptotic reagents in infarcted mouse hearts. The results revealed that the anti-ferroptotic reagent did not improve neonatal heart regeneration, and further compromised the cardiac function of juvenile hearts. On the other hand, ferroptotic cardiomyocytes played a supportive role during wound healing by releasing pro-angiogenic factors. The inhibition of ferroptosis in the regenerating mouse heart altered the immune and angiogenic responses. Our study provides insights into the preference for ferroptosis over other types of RCD in stressed cardiomyocytes, and guidance for designing anti-cell-death therapies for treating heart disease.

Exploring Synergistic Effects of Bioprinted Extracellular Vesicles for Skin Regeneration.

Regenerative medicine represents a paradigm shift in healthcare, aiming to restore tissue and organ function through innovative therapeutic strategies. Among these, bioprinting and extracellular vesicles (EVs) have emerged as promising techniques for tissue rejuvenation. EVs are small lipid membrane particles secreted by cells, known for their role as potent mediators of intercellular communication through the exchange of proteins, genetic material, and other biological components. The integration of 3D bioprinting technology with EVs offers a novel approach to tissue engineering, enabling the precise deposition of EV-loaded bioinks to construct complex three-dimensional (3D) tissue architectures. Unlike traditional cell-based approaches, bioprinted EVs eliminate the need for live cells, thereby mitigating regulatory and financial obstacles associated with cell therapy. By leveraging the synergistic effects of EVs and bioprinting, researchers aim to enhance the therapeutic outcomes of skin regeneration while addressing current limitations in conventional treatments. This review explores the evolving landscape of bioprinted EVs as a transformative approach for skin regeneration. Furthermore, it discusses the challenges and future directions in harnessing this innovative therapy for clinical applications, emphasizing the need for interdisciplinary collaboration and continued scientific inquiry to unlock its full therapeutic potential.