The dermal barrier is widely considered the body’s first line of defense against most foreign bodies, protecting it from both moisture loss and bacterial invasion. However, when the skin is ruptured for long‐term medical interventions (e.g., transcutaneous prosthetics), it is difficult to restore and maintain this protective barrier. Although there are no direct, biological examples of true transcutaneous features in the human body, similar phenomena can be observed in phalangeal nails. This study aims to investigate keratin, the primary component of fingernails, in its hydrolyzed form as an additive to induce cell adhesion in two representative scaffold types. Electrospun fibers and chitosan–gelatin cryogels—two well‐characterized scaffolds used in dermal tissue engineering—were selected for this study as a fibrous and macroporous foundation. Both electrospun fibers and cryogels were fabricated with a range of keratin additive concentrations (0, 1, 3, 5, 7, and 10 wt/wt% and wt/v% for electrospun fibers and cryogels, respectively) and tested for surface properties, mechanical strength, biocompatibility, and material behavior. Overall, it was determined that hydrolyzed keratin had a positive effect on cell adhesion and proliferation but that high quantities of the keratin resulted in adverse effects on the scaffold properties. With dermal applications in mind, this study found that 5 and 7 wt/wt% keratin electrospun fibers possessed required cell counts, surface energies, tensile strength, and contact angle, all with consistent reproducibility. For the cryogels, 3 and 5 wt/v% keratin had the best combined performance, maintained structural integrity through swelling and porosity, and displayed minimal loss in compressive strength. Therefore, hydrolyzed keratin represents a promising additive for bothelectrospun fibers and cryogels in tissue engineering applications.

Decellularized articular cartilage of human origin presents itself as the most homologous filling material for focal cartilage defects. Yet, the full repopulation of the exceptionally dense collagen construct has never been achieved without providing host cells with artificially created migration paths into the matrix. Within this study, we examine the use of a femtosecond laser to engrave fine patterns into human articular cartilage before decellularization and GAG depletion (decell‐deGAG). Scaffolds were tested for decellularization success and mechanical behavior. Seeding tests were performed to assess biocompatibility and examine the performance in a simulated defect environment using an osteochondral plug model in vitro and in vivo in an ectopic nude mouse model. The composition and structure of the newly formed repair tissue and macrophage recruitment were observed via histology. The femtosecond laser was successful in engraving deep, fine structures into the matrix without the thermal damage found with other laser techniques. Engraving was also beneficial for decellularization success. The resulting decell‐deGAG scaffold featured a compressive modulus many times stronger than other biomaterials commonly used for cartilage regeneration and presents a defect filling material that is similar to the tissue it is meant to replace. Moreover, the incisions promoted the repopulation with therapeutically relevant cells. A favorable spatial environment inside the incisions facilitated the formation of repair tissue that mimics hyaline cartilage in composition and collagen orientation. Scaffolds were well‐integrated within simulated defects. Femtosecond laser–engraved cartilage poses an authentic defect filling material with cartilage‐like properties. When used in combination with cell seeding, it promotes the formation of differentiated repair tissue. Thus, the hereby presented biomaterial shows great potential in improving the repair of focal cartilage defects and reducing long‐term graft failures.

Ex vivo organ perfusion (EVOP) is used for whole organ preservation, and the main focus is to improve the outcome of donor organs for transplantation. Recently, EVOP has found application in disease modeling, drug development, and tissue regeneration. We discuss progress in EVOP research involving small animal organs using benchtop and incubator-based EVOP systems, highlighting innovative designs of EVOP systems, technical specifications of each system, and their versatile applications across a range of research fields.

Glycolysis supports mesenchymal stem cell (MSC) proliferation and sustains their undifferentiated state by maintaining energy supply and limiting apoptosis. The rapid advancement of space life sciences has spurred considerable interest in the effects of microgravity on stem cells. However, the contribution of glycolytic metabolism to apoptotic regulation under simulated microgravity (SMG) remains unclear. This study examined the influence of SMG on glycolytic activity and apoptosis in human dental pulp stem cells (hDPSCs). Lactic acid and glucose measurements were used to evaluate glycolytic flux, while transcript levels of HK2, PKM2, and LDHA were quantified by qPCR, HK2 and PKM2 protein expression was assessed by Western blotting, and annexin V‐FITC/PI staining combined with immunoblotting of apoptosis‐related proteins (BAX, BCL‐2, and cleaved caspase‐3) was performed to assess cell death. SMG markedly increased glycolytic capacity and attenuated apoptosis in hDPSCs. SphK1 expression was also elevated, indicating a role in cell survival. Pharmacological inhibition of SphK1 with PF‐543 reduced both glycolysis and the antiapoptotic effect, implicating SphK1 as a critical regulator of these processes. Inhibition of glycolysis by 2‐DG further increased apoptosis, confirming the protective role of glycolytic metabolism under SMG. These findings demonstrate that SMG enhances glycolysis and limits apoptosis in hDPSCs via SphK1 upregulation, suggesting that microgravity conditions may augment stem cell survival and function.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are well established for their osteogenic potential but are prone to senescence with aging or in vitro expansion. Drug treatments that reduce cellular senescence may enhance the regenerative capacity of BM-MSCs. This study investigates the effects of losartan and fisetin, both separately and in combination, on cellular senescence and osteogenesis. Human BM-MSCs were exposed to low and high concentrations of each drug for 24 h. Our findings showed that high-dose losartan exhibited cytotoxicity, focusing subsequent analyses on the low doses. Both low-dose losartan and fisetin effectively mitigated cellular senescence, with combined treatment showing synergistic effects in reducing senescence markers. From these initial findings, subsequent experiments utilized low doses of both compounds to evaluate their effect on differentiation capacity. Our multimodal approach, incorporating flow cytometry, senescence-associated heterochromatin foci (SAHF) immunohistochemistry, senescence-associated secretory phenotype (SASP) quantification, and differentiation potential assays, revealed that the combination of 23.6 μM of losartan and 50 μM of fisetin was optimal for reducing cellular senescence and enhancing osteogenesis in BM-MSCs. These results support potential therapeutic strategies to counteract age-related declines in bone health and improve healing. By targeting cellular senescence while promoting osteogenesis, losartan and fisetin offer promising avenues for future research aimed at enhancing the regenerative capacity of BM-MSCs in the context of musculoskeletal regenerative medicine.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are used to model cardiac development and disease. This requires a robust population of mature CMs and external stimuli to mimic the complex environment of the heart. In effort toward this maturation, previous groups have applied electrical stimulation (ES) to CMs with varying results depending on the stimulation duration, frequency, and pattern. As such, there is an uncertainty surrounding the timeline on which stimulated iPSC-CMs begin to show early signs of maturation in comparison with their nonstimulated counterparts. Here, we introduce a low-cost custom bioreactor capable of delivering tunable ES to standard 2D cell monolayers. We show that, after exposure to short-term ES, stimulated CMs express early signs of maturation compared to nonstimulated controls. Changes to contractility and protein expression indicate cellular rearrangement within cell monolayers and induction of partial maturation in response to ES. While early signs of maturation are present after 3-4 days of ES, additional cellular structures must develop to reach complete maturation. We also show that this bioreactor can electrically stimulate cardiac fibroblasts (cFBs) and may induce alignment of cFB. We have shown that our custom ES bioreactor can be easily integrated into standard in vitro cell culture platforms to induce measurable changes in both CMs and cFB, exhibiting its potential for promoting crucial CM maturation and cell alignment for cardiac tissue engineering applications.

[This retracts the article DOI: 10.1002/term.3184.].

AimsThe aim of this study is to investigate the effects of islet cells and mesenchymal stem cells transferred together in the amniotic membrane (AM) in order to preserve the viability and functionality of islet cells on the success of islet transplantation in diabetes mellitus–induced rats.MethodsA total of 80 male Wistar albino rats, aged 3.5–4 months, were included in this study. While 40 Wistar Albino rats were used for the process of islet cell isolation, 40 Wistar Albino rats were used to establish experimental groups. These rats were assigned to five experimental groups including eight rats in each. These groups were AM, amniotic membrane + mesenchymal stem cell (AM + MSC), amniotic membrane + islet cell (AM + IC), amniotic membrane + islet cell + mesenchymal stem cell (AM + IC + MSC), and sham groups. The study was concluded for 28 days.ResultsAlthough there was no significant difference between AM + IC and AM + IC + MSC groups in terms of mean blood glucose levels, both groups had statistically different values compared to the sham group. A significant difference was observed between the AM + IC and AM + IC + MSC groups in the c‐peptide levels before and after transplantation. Immunohistochemical staining illustrated the presence of insulin‐positive cells in both AM + IC and AM + IC + MSC groups. Moreover, BrDU (+) cells were determined in AM + IC and AM + IC + MSC groups using BrDU staining.ConclusionThe study results indicated that transplanting islet cells into the omentum by being packaged in AM preserved their viability and function, leading to significant effects on blood glucose and c‐peptide levels.

Managing large, critical-sized bone defects poses a complex challenge, especially when autografts are impractical due to their size and limited availability. In such situations, the development of synthetic bone implants becomes crucial. These implants can be carefully designed and manufactured as potential bone substitutes, offering controlled parameters such as porosity, hardness, and osteogenic cues. In this study, we employed digital light processing (DLP) technology to construct an alumina ceramic scaffold featuring a triply periodic minimal surface (TPMS) structure for bone transplantation. The scaffold was filled with type I collagen to enhance cell infiltration [1], thereby increasing the total surface area. In addition, type I collagen is a carrier for both bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA). Using a clinically relevant rabbit cranium defect model, the scaffold underwent in vivo assessment for its functionality in repairing critical-sized bone defect (approximately 8 mm). Four groups of animal experiments were carried out including the control group, the gyroid scaffold group, the type I collagen-loaded scaffold group, and the bioactive factor-functionalized scaffold group. Our animal-based study results revealed that the gyroid scaffold, functionalized with bioactive molecules, provided a conductive surface for promoting increased bone formation and enhancing the healing process in critical-sized long bone and cranium defects. These findings offer preclinical evidence, supporting the use of a TPMS structure composite scaffold and present compelling support for its application as an advanced synthetic bone substitute in the future.

Bone defects are becoming a true challenge in global health care due to the aging population and higher prevalence of musculoskeletal disorders. The interest in using plant-origin compounds and plant-derived biomaterials in bone tissue engineering (BTE) has been increased due to their availability (abundance), safety, biocompatibility, biodegradability, and low cost. Plant-origin compounds have supportive effects on bone tissue healing, and cell-laden plant-derived biomaterials can be applied in formulating bioinks for three-dimensional (3D) bioprinting to facilitate the preparation of native bone tissue-mimicking structures and customized bone scaffolds. Such plant-derived materials also have the capacity to improve cell viability and support osteoconductive and osteoinductive properties of a bone construct. In this article, we review the ethnomedical aspects related to the use of medicinal plants and plant-origin bioactive compounds in bone healing and the recent developments in the 3D bioprinting of bone constructs with plant-derived biomaterials for advancing BTE. The commonly used 3D-bioprinting techniques, the properties of plant-origin compounds and biomaterials (for bone 3D bioprinting), and the selective examples of bone scaffolds fabricated using plant-derived biomaterials are discussed with a special reference set on applicability, performance, advantages, limitations, and challenges. Plant-origin compounds, biomaterials, and biomimetic 3D-bioprinted constructs could be the basis for a next-generation BTE.