Archives of Stem Cell and Regenerative Medicine

Abstract: Asherman syndrome is a gynecologic condition characterized by intrauterine adhesions that impair endometrial regeneration and are associated with infertility, menstrual abnormalities, and adverse reproductive outcomes. Current treatments, including hysteroscopic adhesiolysis and hormonal therapy, primarily aim to restore uterine cavity structure but often fail to achieve full functional regeneration of the endometrium, particularly in patients with moderate to severe disease. This paper examines the underlying pathophysiology of Asherman syndrome, emphasizing the role of basal layer damage, impaired vascularization, fibrosis, and disrupted stem cell activity in limiting endometrial repair. Stem cell–based therapies have emerged as a promising regenerative approach to address these limitations. Evidence from preclinical models demonstrates that mesenchymal stem cells and related therapies can promote angiogenesis, reduce fibrosis, enhance cellular proliferation, and improve endometrial thickness and gland formation. Early clinical studies further suggest improvements in menstrual function, endometrial receptivity, and pregnancy outcomes in patients with treatment-resistant disease. However, current findings remain limited by heterogeneity in study design, variability in cell sources and delivery methods, and a lack of standardized protocols and long-term safety and efficacy data. Overall, stem cell–based therapies represent a potential shift toward regenerative treatment strategies for Asherman syndrome. Continued research focused on standardization, optimization of delivery systems, and large-scale clinical trials will be essential to determine their clinical applicability and long-term impact on reproductive outcomes.

Abstract: This study develops a reduced-order, physics-informed framework for analyzing and optimizing drug delivery in a vascular environment by coupling hemodynamic flow dynamics with pharmacokinetic transport. The blood flow field is represented using a Hopf-type nonlinear oscillator derived from reduced Navier–Stokes dynamics, capturing the emergence of oscillatory flow states that significantly influence mixing and transport. This fluid subsystem is directly coupled to a two-compartment pharmacokinetic model that describes drug concentration evolution in plasma and surrounding tissue. The resulting system accounts for convection-enhanced dispersion, inter-compartmental mass transfer, and systemic clearance, thereby providing a more realistic representation of in vivo drug transport than classical compartmental approaches. Bifurcation analysis reveals a Hopf bifurcation that governs the transition between steady and oscillatory flow regimes, which in turn modulates drug dispersion and tissue uptake efficiency. The interaction between flow instability and drug transport is shown to play a critical role in determining concentration profiles in both plasma and tissue compartments. Furthermore, the framework enables the study of how flow-induced mixing can enhance or impair therapeutic delivery depending on system parameters. An optimal control formulation is developed to regulate drug concentration and flow activity, with and without bifurcation-aware constraints. The results demonstrate that incorporating stability constraints improves performance and controls drug distribution, reducing undesirable concentration fluctuations while maintaining effective tissue delivery. The proposed approach provides a unified computational framework integrating nonlinear dynamics, transport physics, and control theory, offering new insights into the role of hemodynamic instabilities in drug delivery systems and enabling improved therapeutic design strategies.