D. Pavlidis

Ovarian tissue cryopreservation and transplantation (OTCT) restores fertility and ovarian endocrine function in patients exposed to gonadotoxic cancer therapies but graft outcomes remain variable due to the avascular nature of the transplantation procedure. Here, the host‐graft interface is engineered using a synthetic microporous annealed particle (MAP) hydrogel transplantation strategy to support vascular integration of human ovarian tissue cubes. In a xenograft model of primary ovarian insufficiency (POI), non‐encapsulated ovarian tissue strips exhibit early but transient and disorganized host vascular infiltration. In contrast, tissue cubes encapsulated within MAP hydrogels (OvaMAPs) demonstrate sustained host vascular integration with significantly greater mouse vessel area and length at 3 and 6 weeks post‐transplantation. By 20 weeks, both non‐encapsulated grafts and OvaMAPs restore circulating estradiol and suppress follicle‐stimulating hormone, confirming integration of the grafts with the host hypothalamic‐pituitary axis. Notably, OvaMAP recipients exhibit reduced variability in estradiol levels, suggesting consistent, predictable graft function. These findings identify stabilization of vascular remodeling at the host‐graft interface as a key determinant of ovarian graft performance and demonstrate that a fully synthetic microporous biomaterial can improve the durability and predictability of endocrine function restoration after OTCT for patients at risk of POI.

Rapid revascularization is critical to tissue graft survival, as delayed reperfusion drives tissue ischemia and compromises cell viability and graft function. Although bulk hydrogels have been explored for promoting vessel formation, vascularization remains too slow to prevent ischemic injury to grafted tissues, highlighting the need for biomaterial platforms that accelerate graft revascularization and reperfusion. In this study, we present granular hydrogel composites (GHCs), where interstitial space is filled with fibrin and collagen to provide a vasculogenic matrix environment. GHCs supported the assembly of embedded endothelial cells into interconnected, lumenized networks in vitro which anastomosed with host vasculature and were systemically perfused 7 days after implantation. Careful optimization studies revealed that GHCs formed from covalently interlinked, RGD-functionalized microgels of 115 µm diameter best supported vascular network formation in vitro and intravascular blood perfusion in vivo . To test the utility of GHCs for the vascular integration of a demanding and therapeutically relevant parenchymal tissue, GHC-based ovarian tissue grafts were implanted in a murine xenograft model and successfully connected to host vasculature, restoring blood flow to embedded human ovarian tissues within 10 days post-implantation. Notably, endothelial cells seeded within GHCs formed viable vasculature without pre-culture. This work establishes GHCs as a biomaterial platform to rapidly connect parenchymal tissues to host vasculature, with broad translational potential across engineered tissue grafting applications.

Over the past decade, the integration of microgel-based granular hydrogels in biomedical technologies has experienced substantial growth due to the numerous benefits microgels offer. However, the inability to easily adopt uniform microgel fabrication workflows at scale constitutes a major bottleneck, or in some cases, a barrier-to-entry that stunts further growth of the field. The gold-standard technique for emulsion-based microgel production is through microfluidic droplet-generating devices that produce liquid gel precursor droplets that gel post-production. However, traditional microfluidic workflows often require multiple independent flows and controlled pressure sources, along with a steep learning curve in using microfluidics to achieve uniform droplet sizes reproducibly and repeatedly. This difficulty in adopting microgel fabrication is further compounded by low throughput and the extensive flow rate calibration required when switching to new formulations (e.g., material type, droplet size). In this work, we present a step-emulsion system that bridges the gap by providing a robust and simple setup. We experimentally characterize and evaluate how flow and outlet channel dimension contribute to the generation of uniform droplet populations at specific sizes. With our large dataset consisting of various outlet channel dimensions, we evaluated outlet channel geometrical impacts (height, width, cross-sectional area, aspect-ratio, etc.) on gel precursor droplet size and generation throughput. We demonstrate robust, highly compatible, and repeatably uniform droplet generation from various gel precursor polymer backbones, users with varying microfluidics experience, and a wide viscosity range, including alginate solutions with 650 times the viscosity of water. Furthermore, we confirmed consistent gel precursor droplet generation outcomes driven by a constant flow source (syringe pump) and by direct manual injection as a simple and highly adoptable option for the generation of gel precursor droplets. This platform is ideal for researchers seeking rapid and easy microgel fabrication, regardless of microfluidics experience.

Pediatric cancer survivors treated with gonadotoxic chemotherapy or radiation face lifelong premature ovarian insufficiency (POI), leading to elevated risk of cardiovascular disease, osteoporosis, and metabolic dysfunction. Pharmacological hormone replacement therapy (HRT) cannot replicate the pulsatile, bidirectional signaling of the hypothalamic-pituitary-gonadal (HPG) axis, leaving a critical therapeutic gap. Immune-isolating hydrogel capsules offer a promising strategy for the implantation of donor ovarian tissue without immunosuppression yet they require optimization for human applications. Here, we engineer a microporous immune-isolating capsule by incorporating thermosensitive gelatin microgels as sacrificial porogens. Microfluidic fabrication yielded monodisperse microgels that dissolved at 37°C generating disconnected micropores within a non-degradable poly(ethylene glycol) (PEG) matrix. Critically, the diffusion of FSH-scale analogs (40 kDa) increased by almost two-fold through the microporous capsules relative to nanoporous controls, while antibody-scale molecules (150 kDa) were blocked, demonstrating size-discriminating permeability. In ovariectomized mice implanted with encapsulated ovarian xenografts for 20 weeks, microporous capsules restored dynamic HPG-axis signaling evidenced by elevated levels of estradiol and progesterone, FSH suppression, and fluctuating hormone levels that resembled physiological patterns. Microporosity also improved graft viability, increasing stromal cellularity and reducing follicular apoptosis. These findings support microporous immune-isolating capsules as a platform for physiologically authentic therapy for POI.

Research question: Can tissue clearing, combined with volumetric imaging, enable reliable, quantitative three-dimensional analysis of follicles and vasculature in intact human ovarian tissue? Design: A CUBIC-based clearing protocol was adapted for human ovarian medulla and cryopreserved cortex. Tissue from reproductive-aged donors was cleared, fluorescently labeled, and imaged using confocal and light sheet microscopy. Tissue expansion, imaging depth, and vascular morphometrics were quantified and follicle density was compared to conventional histology. Results: Clearing produced optically transparent tissue with a linear expansion factor of 1.2 across cortex and medulla. Imaging depth increased 6.5–11-fold in cortex and 6–8-fold in medulla. Follicle density measurements in immunolabeled cleared cortex were comparable to histology, supporting the validity of volumetric follicle quantification. Light sheet microscopy of lectin-labeled cortex revealed no significant donor-to-donor differences in vascular morphometrics, including mean vessel diameters of 12–14 µm, branch point densities of 632–965 points/mm ³ , vessel length densities of 117–175 mm/mm ³ , and volume fractions of 1.9–2.3%. Volumetric imaging further illustrated heterogeneous spatial relationships between follicles and surrounding vessels. Conclusion: Tissue clearing and volumetric imaging complement routine histology and enable quantitative three-dimensional investigation of follicle-vascular interactions in intact human ovarian tissue, providing a framework for advancing fertility preservation and ovarian tissue transplantation research.

Premature loss of ovarian function (POI) is associated with numerous negative side effects, including vasomotor symptoms, sleep and mood disturbances, disrupted urinary function, and increased risks for osteoporosis and heart disease. Hormone replacement therapy (HRT), the standard of care for POI, delivers only a subset of ovarian hormones and fails to mimic the monthly cyclicity and daily pulsatility characteristic of healthy ovarian tissue in reproductive-aged individuals whose ovarian tissue contains thousands of ovarian follicles. Ovarian tissue allografts have the potential to serve as an alternative, cell-based HRT, capable of producing the full panel of ovarian hormones at physiologically relevant doses and intervals. However, the risks associated with systemic immune suppression (IS) required to prevent allograft rejection outweigh the potential benefits of comprehensive and dynamic hormone therapy. This work investigates whether the age of ovarian tissue donor animals affects the function of, and immune response to, subcutaneous ovarian grafts. We performed syngeneic and semi-allogeneic ovarian transplants using tissue from mice aged 6–8 (D7) or 20–22 (D21) days and evaluated ovarian endocrine function and immune response in a mouse model of POI. Our results revealed that tissue derived from D7 donors, containing an ample and homogeneous primordial follicle reserve, was more effective in fully restoring hypothalamic–pituitary–ovarian feedback. In contrast, tissue derived from D21 donors elicited anti-donor antibodies with higher avidity compared to tissue from younger donors, suggesting that greater immunogenicity may be a trade-off of using mature donors. This work contributes to our understanding of the criteria donor tissue must meet to effectively function as a cell-based HRT and explores the importance of donor age as a factor in ovarian allograft rejection.

Degradation prediction of AlGaN/GaN MODFET is explored based on characterization of gate and drain low- frequency noise. Heterostructures grown by molecular beam epitaxy (MBE) and metal-organic chemical vapor deposition (MOCVD) are used for this purpose. Devices from the former category were unpassivated while those of the latter were passivated. Despite the highly variable gate noise current characteristics among unpassivated MBE devices and between MBE and MOCVD-based devices, it is demonstrated that the drain noise current characteristics of the two groups of devices have considerable resemblance. Moreover, it is shown that the drain noise current level can be used as a means for gate degradation prediction

A 3–16 GHz wideband AlGaN/GaN high electron mobility transistor (HEMT) low noise amplifier (LNA) on silicon carbide substrate, using balanced configuration with a coplanar waveguide Lange coupler, is designed and fabricated. This LNA shows a minimum noise figure of 4 dB with associated gain of 20 dB with gain flatness of ±3 dB across the 3–16 GHz frequency range. The output third order intercept point of 38 dBm is achieved at 8 GHz.

The microwave power performance of InP/GaAsSb/InP double heterojunction bipolar transistors (DHBTs) was evaluated and is reported for the first time. Fabricated DHBTs showed DC gain of 15-35, small turn-on voltages of 0.44 V at 1 kA/cm/sup 2/ , almost zero offset voltage, and emitter-collector breakdown voltage BV/sub CEO/ /spl ges/ 6 V. Devices with 3/spl times/5 /spl mu/m/sup 2/ emitters showed maximum f/sub T/ of 75 GHz and maximum f/sub max/ of 34 GHz when biased at J/sub C/ =1.7/spl times/10/sup 5/ A/cm/sup 2/ and V/sub CE/ =2.0 V. Devices with 5/spl times/10 /spl mu/m/sup 2/ emitters demonstrated power gain of 10 dB with 1 dB-compressed output power of 18 dBm at 5 GHz. High power density of 1.6 mW//spl mu/m/sup 2/ and associated efficiency of 33% were obtained using these devices.