Recently, biomedicine and tissue regeneration have emerged as great advances that impacted the spectrum of healthcare. This left the door open for further improvement of their applications to revitalize the impaired tissues. Hence, restoring their functions. The implementation of therapeutic protocols that merge biomimetic scaffolds, bioactive molecules, and cells plays a pivotal role in this track. Smart/stimuli-responsive hydrogels are remarkable three-dimensional (3D) bioscaffolds intended for tissue engineering and other biomedical purposes. They can simulate the physicochemical, mechanical, and biological characters of the innate tissues. Also, they provide the aqueous conditions for cell growth, support 3D conformation, provide mechanical stability for the cells, and serve as potent delivery matrices for bioactive molecules. Many natural and artificial polymers were broadly utilized to design these intelligent platforms with novel advanced characteristics and tailored functionalities that fit such applications. In the present review, we highlighted the different types of smart/stimuli-responsive hydrogels with emphasis on their synthesis scheme. Besides, the mechanisms of their responsiveness to different stimuli were elaborated. Their potential for tissue engineering applications was discussed. Furthermore, their exploitation in other biomedical applications as targeted drug delivery, smart biosensors, actuators, 3D and 4D printing, and 3D cell culture were outlined. In addition, we threw light on smart self-healing hydrogels and their applications in biomedicine. Eventually, we presented their future perceptions in biomedical and tissue regeneration applications. Conclusively, current progress in the design of smart/stimuli-responsive hydrogels enhances their prospective to function as intelligent, and sophisticated systems in different biomedical applications.

Modified uridine containing taurine, 5-taurinomethyluridine (τm⁵U), is found at the anticodon first position of mitochondrial (mt-)transfer RNAs (tRNAs). Previously, we reported that τm⁵U is absent in mt-tRNAs with pathogenic mutations associated with mitochondrial diseases. However, biogenesis and physiological role of τm⁵U remained elusive. Here, we elucidated τm⁵U biogenesis by confirming that 5,10-methylene-tetrahydrofolate and taurine are metabolic substrates for τm⁵U formation catalyzed by MTO1 and GTPBP3. GTPBP3-knockout cells exhibited respiratory defects and reduced mitochondrial translation. Very little τm⁵U34 was detected in patient’s cells with the GTPBP3 mutation, demonstrating that lack of τm⁵U results in pathological consequences. Taurine starvation resulted in downregulation of τm⁵U frequency in cultured cells and animal tissues (cat liver and flatfish). Strikingly, 5-carboxymethylaminomethyluridine (cmnm⁵U), in which the taurine moiety of τm⁵U is replaced with glycine, was detected in mt-tRNAs from taurine-depleted cells. These results indicate that tRNA modifications are dynamically regulated via sensing of intracellular metabolites under physiological condition.

Biomedicine and tissue regeneration have made significant advancements recently, positively affecting the whole healthcare spectrum. This opened the way for them to develop their applications for revitalizing damaged tissues. Thus, their functionality will be restored. Cardiac tissue engineering (CTE) using curative procedures that combine biomolecules, biomimetic scaffolds, and cells plays a critical part in this path. Stimuli-responsive hydrogels (SRHs) are excellent three-dimensional (3D) biomaterials for tissue engineering (TE) and various biomedical applications. They can mimic the intrinsic tissues’ physicochemical, mechanical, and biological characteristics in a variety of ways. They also provide for 3D setup, adequate aqueous conditions, and the mechanical consistency required for cell development. Furthermore, they function as competent delivery platforms for various biomolecules. Many natural and synthetic polymers were used to fabricate these intelligent platforms with innovative enhanced features and specialized capabilities that are appropriate for CTE applications. In the present review, different strategies employed for CTE were outlined. The light was shed on the limitations of the use of conventional hydrogels in CTE. Moreover, diverse types of SRHs, their characteristics, assembly and exploitation for CTE were discussed. To summarize, recent development in the construction of SRHs increases their potential to operate as intelligent, sophisticated systems in the reconstruction of degenerated cardiac tissues.

Dilated cardiomyopathy (DCM) is characterized by ventricular dilation associated with systolic dysfunction, which could be caused by mutations in lamina/C gene (LMNA). LMNA-linked DCM is severe in males in both human patients and a knock-in mouse model carrying a homozygous p.H222P mutation (Lmna^H222P/H222P). The aim of this study was to investigate the molecular mechanisms underlying the gender difference of LMNA-linked DCM. A whole-exome analysis of a multiplex family with DCM exhibiting the gender difference revealed a DCM-linked LMNA mutation, p.R225X. Immunohistochemical analyses of neonatal rat cardiomyocytes expressing mutant LMNA constructs and heart samples from the LMNA-linked DCM patients and Lmna^H222P/H222P mice demonstrated a nuclear accumulation of androgen receptor (AR) and its co-activators, serum response factor, and four-and-a-half LIM protein-2. Role of sex hormones in the gender difference was investigated in vivo using the Lmna^H222P/H222P mice, where male and female mice were castrated and ovariectomized, respectively, or treated with testosterone or an antagonist of AR. Examination of the mice by echocardiography, followed by the analyses of histological changes and gene/protein expression profiles in the hearts, confirmed the involvement of testicular hormone in the disease progression and enhanced cardiac remodelling in the Lmna^H222P/H222P mice. These observations indicated that nuclear accumulation of AR was associated with the gender difference in LMNA-linked DCM.