Biology subjects

Ameer, G.

Publications and source records attributed to Ameer, G..

9 recordsLinked to original sources

bioRxiv2026

Healing cascades and infections in wounds monitored using a wearable sensor of gaseous flux

Capabilities for quantitative monitoring of chronic wounds remain an unmet clinical need, as existing diagnostic approaches rely on semiquantitative evaluation of symptoms that lack sensitivity especially during early stages of infection. Here we present a scheme for tracking wound physiology that leverages a miniature, wireless skin-interfaced device for non-contact, transient measurements of the flux of volatile organic compounds (VOCs) and water vapor from the wound microenvironment. Unlike emerging smart bandage platforms that rely on physical contact with the fragile wound bed to interrogate liquid-phase biomarkers, this strategy uses an engineered microclimate and suspended suite of sensors to measure the diffusive transport of wound-derived gases across the wound surface but separated from it. The result enables quantitative evaluation of metabolic activity and healing progression without perturbing the healing tissues. In biofilm growth models of Staphylococcus aureus, measurements demonstrate that trends in VOC flux correlate strongly with bacterial growth kinetics and precede any visible biofilm formation. Longitudinal monitoring in infected murine wound healing models shows that concurrent measurements of water vapor and VOC flux provide complementary physiological insights, capturing both the trajectory of barrier restoration and the dynamics of bacterial burden. The findings establish this non-contact sensing scheme as a distinct and clinically translatable paradigm for wound monitoring, with broad implications for non-invasive surveillance of disease states in which tissue metabolic activity and skin barrier integrity serve as actionable physiological readouts. Significance StatementLimited capabilities in continuous, quantitative assessment of a wound make early diagnosis and effective management challenging, particularly in cases of infection that rapidly progress before symptoms appear. Non-contact approaches for wound monitoring that preserve fragile tissue can transform wound care. In this context, gaseous flux from the wound bed provides an integrative measure of microbial activity and barrier restoration. This study establishes a wearable sensing platform that quantifies these fluxes in real time, enabling early infection detection and temporal tracking of wound healing. These results highlight a path toward personalized treatment strategies and reduced reliance on episodic clinical evaluation.

bioengineering↗

bioRxiv2026

A Pro-Regenerative Petroleum Jelly-Based, Copper-Doped Bioactive Glass Ointment for Impaired Wound Healing in Metabolic Syndrome

Chronic wound healing is often impaired in conditions such as metabolic syndrome, requiring effective therapeutic interventions to promote tissue regeneration and repair. In this study, we evaluated the wound healing potential of petroleum jelly (P Jelly)-based bioactive glass ointments (PBGCu) with varying copper concentrations (0, 1, and 3 wt%) in both in vitro and in vivo models of wound healing. PBGCu formulations demonstrated high biocompatibility with human dermal fibroblasts (HDF) and human umbilical vein endothelial cells (HUVEC). Additionally, PBGCu ointments exhibited strong antibacterial activity against Staphylococcus aureus, suggesting their utility for the care of chronic wounds. In both metabolic syndrome mouse and pig models, PBGCu3-treated wounds showed significantly faster wound closure, enhanced epithelial regeneration, and increased dermal thickness compared to saline and P Jelly controls. Histological analysis also revealed 50% increased vascularization (p < 0.0001) and a 90% reduction in scar formation (p < 0.0001) in PBGCu3-treated wounds. These findings show that PBGCu formulations, especially at 3 wt% copper concentration, significantly improve wound healing by promoting epithelial regeneration, dermal tissue formation, and vascularization, while also offering antibacterial protection. The sustained Cu2+ ions release from PBGCu ointments provides long-term support for tissue regeneration, positioning this ointment composition as a promising therapeutic tool for chronic wound management. Future studies will focus on elucidating the underlying mechanisms and evaluating the therapeutic efficacy of PBGCu formulations in infected wounds. HighlightsO_LIDeveloped a Petroleum Jelly-based copper-doped bioactive glass ointment (PBGCu) enabling sustained and controlled Cu{superscript 2} ion release. C_LIO_LIPBGCu significantly accelerated wound closure and improved epithelial and dermal tissue regeneration. C_LIO_LIPBGCu enhanced hair follicle regeneration and tissue remodeling in full-thickness wounds. C_LIO_LIValidated therapeutic efficacy in both mouse and pig models that support translational relevance. C_LIO_LIOffers a simple, low-cost, and clinically adaptable topical formulation for metabolic syndrome-related wound complications. C_LI

bioengineering↗

bioRxiv2024

Leveraging chromatin packing domains to target chemoevasion in vivo

Cancer cells exhibit a remarkable resilience to cytotoxic stress, often adapting through transcriptional changes linked to alterations in chromatin structure. In several types of cancer, these adaptations involve epigenetic modifications and restructuring of topologically associating domains (TADs). However, the underlying principles by which chromatin architecture facilitates such adaptability across different cancers remain poorly understood. To investigate the role of chromatin in this process, we developed a physics-based mechanistic model that connects chromatin organization to cell fate decisions, specifically survival following chemotherapy. Our model builds on the observation that chromatin forms packing domains, which influence transcriptional efficiency through macromolecular crowding. The model accurately predicts chemoevasion in vitro, suggesting that changes in packing domains affect the likelihood of survival. Consistent results across diverse cancer types indicate that the model captures fundamental principles of chromatin-mediated adaptation, independent of the specific cancer or chemotherapy mechanisms involved. Based on these insights, we hypothesized that compounds capable of modulating packing domains, termed Transcriptional Plasticity Regulators (TPRs), could prevent cellular adaptation to chemotherapy. Using live-cell chromatin imaging, we conducted a compound screen that identified several TPRs which synergistically enhanced chemotherapyinduced cell death. The most effective TPR significantly improved therapeutic outcomes in a patient-derived xenograft (PDX) model of ovarian cancer. These findings underscore the central role of chromatin in cellular adaptation to cytotoxic stress and present a novel framework for enhancing cancer therapies, with broad potential across multiple cancer types.

biophysics↗

bioRxiv2024

3D Printing of Multiscale Scaffolds with Microtopography for Guiding Tissue Organization and Regeneration

Engineering biomaterial scaffolds with multiscale structures, integrating anatomically accurate macroscale architecture (millimeters to centimeters) with microtopographic features (sub-microns to tens of microns), is critical for guiding cellular organization and tissue regeneration. However, fabricating such multiscale scaffolds remains challenging due to the limitations of conventional manufacturing techniques and the trade-off between speed and resolution in current 3D printing methods. Here, we present a multiscale micro-continuous liquid interface production (M{micro}CLIP) technique that enables rapid, one-step 3D printing of centimeter-scale scaffolds with spatially tunable microtopography of various sizes and geometries in just a few minutes (up to 1 mm/min). To showcase the versatility of our technique, we printed a one-centimeter-long tubular scaffold with dual microtopographic patterns, i.e. 20 {micro}m axially aligned grooves on the internal surface and 15 {micro}m circumferentially aligned rings on the external surface. These scaffolds induced the simultaneous orientation of vascular endothelial cells along the axial grooves and vascular smooth muscle cells along the circumferential rings, mimicking the orthogonally aligned bilayer architecture of natural arteries. Moreover, the groove patterns significantly accelerated endothelial cell migration, potentially enhancing endothelialization in vascular implants. This approach provides a versatile tool for designing advanced scaffolds and medical devices that harness microtopography to guide tissue organization and enhance regeneration.

bioengineering↗

bioRxiv2024

Personalized composite scaffolds for accelerated cell- and growth factor-free craniofacial bone regeneration

Approaches to regenerating bone often rely on the integration of biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches face challenges due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation. The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite. Using a continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60% hydroxyapatite content resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite, customizable in situ to fit the defect. This hybrid phasic porous CSS mimics the bone microenvironment (inorganic and organic) while allowing independent control of each material phase (rigid and soft). The CSS stimulates osteogenic differentiation in vitro and in vivo. Moreover, it promotes M2 polarization and blood vessel ingrowth, which are crucial for supporting bone formation. Our comprehensive micro-CT analysis revealed that within 4 weeks in a critical-size defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.

bioengineering↗

bioRxiv2024

A biodegradable microgrooved and tissue mechanocompatible citrate-based scaffold improves bladder tissue regeneration

Chronic bladder dysfunction due to bladder disease or trauma is detrimental to affected patients as it can lead to increased risk of upper urinary tract dysfunction. Current treatment options include surgical interventions that enlarge the bladder with autologous bowel tissue to alleviate pressure on the upper urinary tract. This highly invasive procedure, termed bladder augmentation enterocystoplasty (BAE), significantly increases the risk of patient morbidity and mortality due to the incompatibility between the bowel and bladder tissue. Therefore, patients would significantly benefit from an alternative treatment strategy that can regenerate healthy tissue and restore overall bladder function. Previous research has demonstrated the potential of citrate-based scaffolds co-seeded with bone marrow-derived stem/progenitor cells as an alternative graft for bladder augmentation. Recognizing that contact guidance can potentially influence tissue regeneration, we hypothesized that patterned scaffolds would modulate cell responses and improve overall quality of the regenerated bladder tissue. We fabricated microgrooved (MG) scaffolds using the citrate-based biomaterial poly(1,8-octamethylene-citrate-co-octanol) (POCO) and co-seeded them with human bone marrow-derived mesenchymal stromal cells (MSCs) and CD34+ hematopoietic stem/progenitor cells (HSPCs). Microgrooved POCO scaffolds supported MSC and HSPC attachment, and MSC alignment within the microgrooves. All scaffolds were characterized and assessed for bladder tissue regeneration in an established nude rat bladder augmentation model. In all cases, normal physiological function was maintained post-augmentation, even without the presence of stem/progenitor cells. Urodynamic testing at 4-weeks post-augmentation for all experimental groups demonstrated that bladder capacity increased and bladder compliance was normal. Histological evaluation of the regenerated tissue revealed that cell-seeded scaffolds restored normal bladder smooth muscle content and resulted in increased revascularization and peripheral nerve regeneration. The presence of microgrooves on the cell-seeded scaffolds increased microvasculature formation by 20% and urothelium layer thickness by 25% in the regenerating tissue. Thus, this work demonstrates that micropatterning affects bladder regeneration to improve overall anatomical structure and re-establish bladder physiology.

bioengineering↗

bioRxiv2023

3D-printed, Citrate-based Bioresorbable Vascular Scaffolds for Coronary Artery Angioplasty

Fully bioresorbable vascular scaffolds (BVSs) were designed to overcome the limitations of metallic drug-eluting stents (DESs). However, current polymer-based BVSs, such as Abbotts Absorb, the only US FDA-approved BVS, struggle with increased strut thickness (150 m for Absorb) and exacerbated tissue inflammation, leading to inferior clinical performance compared to metallic DESs. Here we develop a drug-eluting BVS (DE-BVS) through the innovative use of photopolymerizable, citrate-based materials and high-precision additive manufacturing process. Bare BVS with a clinically relevant strut thickness of 62 m can be produced in a high-throughput manner, i.e. one BVS per minute. By modulating the coating polymer and structure, we achieve a controlled release of anti-restenosis drug of everolimus from DE-BVSs. We show the mechanical competence of DE-BVS and the successful deployment in swine coronary arteries using a custom-built balloon catheter delivery system. We further demonstrate that BVS and DE-BVS remain safe and effective to keep the vessel patency, induce limited inflammation, and facilitate the recovery of smooth muscle and endothelial tissues over 28 days implantation in swine coronary arteries. All these evaluated pre-clinical performances are largely comparable to the commercial XIENCE DES (Abbott Vascular).

bioengineering↗

bioRxiv2023

Investigation of 3D Printed Bioresorbable Vascular Scaffold Crimping Behavior

The rise in additive manufacturing (AM) offers myriad opportunities for 3D-printed polymeric vascular scaffolds, such as customization and on-the-spot manufacturing, in vivo biodegradation, incorporation of drugs to prevent restenosis, and visibility under X-ray. To maximize these benefits, informed scaffold design is critical. Polymeric bioresorbable vascular scaffolds (BVS) must undergo significant deformation prior to implantation in a diameter-reduction process known as crimping which enables minimally invasive surgery. Understanding the behavior of vascular scaffolds in this step provides twofold benefits: first, it ensures the BVS is able to accommodate stresses occurring during this process to prevent failure, and further, it provides information on the radial strength of the BVS, a key metric to understanding its post-implant performance in the artery. To capitalize on the fast manufacturing speed AM provides, a low time cost solution for understanding scaffold performance during this step is necessary. Through simulation of the BVS crimping process in ABAQUS using experimentally obtained bulk material properties, we have developed a qualitative analysis tool which is capable of accurately comparing relative performance trends of varying BVS designs during crimping in a fraction of the time of experimental testing, thereby assisting in the integration of informed design into the additive manufacturing process.

bioengineering↗

bioRxiv2020

Subcutaneous nanotherapy repurposes the immunosuppressive mechanism of rapamycin to enhance allogeneic islet graft viability

Oral rapamycin administration rapamycin is plagued by poor bioavailability and wide biodistribution. Thus, this pleotropic mTOR inhibitor has a narrow therapeutic window, numerous side effects and provides inadequate transplantation protection. Parental formulation was not possible due to rapamycins hydrophobicity (log P 4.3). Here, we demonstrate that subcutaneous rapamycin delivery via poly(ethylene glycol)-b-poly(propylene sulfide)(PEG-b-PPS) polymersome (PS) nanocarriers modulates cellular biodistribution of rapamycin to change its immunosuppressive mechanism for enhanced efficacy while minimizing side effects. While oral rapamycin inhibits naive T cell proliferation directly, subcutaneously administered rapamycin-loaded polymersomes (rPS) instead modulated Ly-6Clow monocytes and tolerogenic semi-mature dendritic cells, with immunosuppression mediated by CD8+ Tregs and rare CD4+ CD8+ double-positive T cells. As PEG-b-PPS PS are uniquely non-inflammatory, background immunostimulation from the vehicle was avoided, allowing immunomodulation to be primarily attributed to rapamycins cellular biodistribution. Repurposing mTOR inhibition significantly improved maintenance of normoglycemia in a clinically relevant, MHC-mismatched, allogeneic, intraportal (liver) islet transplantation model. These results demonstrate the ability of engineered nanocarriers to repurpose drugs for alternate routes of administration by rationally controlling cellular biodistribution.

bioengineering↗