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Laura Pandolfi, PhD, MBA
Genf, Genf, Schweiz
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I am a Business Development Executive and CDMO expert who partners with global pharma &…
Aktivitäten
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The MBA in International Healthcare Management partners with world class institutions. On our recent #Singapore module, the NUS Yong Loo Lin School…
The MBA in International Healthcare Management partners with world class institutions. On our recent #Singapore module, the NUS Yong Loo Lin School…
Beliebt bei Laura Pandolfi, PhD, MBA
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Hello Korea! Nice to be back for #cphikorea #adare. Looking forward to meeting you all....
Hello Korea! Nice to be back for #cphikorea #adare. Looking forward to meeting you all....
Beliebt bei Laura Pandolfi, PhD, MBA
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When Christoph Staub speaks, you can take it to the bank! 💪 #digitalassetmanagement #digitalization #machinerymanufacturing #maintenance
When Christoph Staub speaks, you can take it to the bank! 💪 #digitalassetmanagement #digitalization #machinerymanufacturing #maintenance
Beliebt bei Laura Pandolfi, PhD, MBA
Berufserfahrung
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Veröffentlichungen
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Electrospun Patch Functionalized with Nanoparticles Allows for Spatiotemporal Release of VEGF and PDGF-BB Promoting In Vivo Neovascularization
ACS Applied Materials & Interfaces
The use of nanomaterials as carriers for the delivery of growth factors has been applied to a multitude of applications in tissue engineering. However, issues of toxicity, stability, and systemic effects of these platforms have yet to be fully understood, especially for cardiovascular applications. Here, we proposed a delivery system composed of poly(dl-lactide-co-glycolide) acid (PLGA) and porous silica nanoparticles (pSi) to deliver vascular endothelial growth factor (VEGF) and…
The use of nanomaterials as carriers for the delivery of growth factors has been applied to a multitude of applications in tissue engineering. However, issues of toxicity, stability, and systemic effects of these platforms have yet to be fully understood, especially for cardiovascular applications. Here, we proposed a delivery system composed of poly(dl-lactide-co-glycolide) acid (PLGA) and porous silica nanoparticles (pSi) to deliver vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The tight spatiotemporal release of these two proteins has been proven to promote neovascularization. In order to minimize tissue toxicity, localize the release, and maintain a stable platform, we conjugated two formulations of PLGA–pSi to electrospun (ES) gelatin to create a combined ES patch releasing both PDGF and VEGF. When compared to freely dispersed particles, the ES patch cultured in vitro with neonatal cardiac cells had significantly less particle internalization (2.0 ± 1.3%) compared to free PLGA–pSi (21.5 ± 6.1) or pSi (28.7 ± 2.5) groups. Internalization was positively correlated to late-stage apoptosis with PLGA–pSi and pSi groups having increased apoptosis compared to the untreated group. When implanted subcutaneously, the ES patch was shown to have greater neovascularization than controls evidenced by increased expression of α-SMA and CD31 after 21 days. Quantitative reverse transcription–polymerase chain reaction results support increased angiogenesis by the upregulation of VEGFA, VEGFR2, vWF, and COL3A1, exhibiting a synergistic effect with the release of VEGF-A164 and PDGF-BB after 21 days in vivo. The results of this study proved that the ES patch reduced cellular toxicity and may be tailored to have a dual release of growth factors promoting localized neovascularization.
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Controlled Release of Small Molecules for Cardiac Differentiation of Pluripotent Stem Cells
Tissue Engineering Part A
Induced pluripotent stem cells (iPSCs) have been shown to differentiate to functional cardiomyocytes (CM) with high efficiency through temporally controlled inhibition of the GSK3/Wnt signaling pathways. In this study, we investigated the ability of temporally controlled release of GSK3/Wnt small-molecule inhibitors to drive cardiac differentiation of iPSC without manual intervention. Porous silica particles were loaded with GSK3 inhibitor CHIR99021 or Wnt inhibitor IWP2, and the particles…
Induced pluripotent stem cells (iPSCs) have been shown to differentiate to functional cardiomyocytes (CM) with high efficiency through temporally controlled inhibition of the GSK3/Wnt signaling pathways. In this study, we investigated the ability of temporally controlled release of GSK3/Wnt small-molecule inhibitors to drive cardiac differentiation of iPSC without manual intervention. Porous silica particles were loaded with GSK3 inhibitor CHIR99021 or Wnt inhibitor IWP2, and the particles containing IWP2 were coated with 5 wt% poly(lactic-co-glycolic acid) 50:50 to delay release by ∼72 h. iPSCs reprogrammed through mRNA transfection were cultured with these particles up to 30 days. High-performance liquid chromatography suggests a burst release of CHIR99021 within the first 24 h and a delayed release of IWP2 after 72 h. Annexin V/propidium iodide staining did not show a significant effect on apoptosis or necrosis rates. Cultured cells upregulated both early (Nkx 2.5, Isl-1) and late (cTnT, MHC, Cx43) cardiac markers, assayed with a quantitative real-time polymerase chain reaction, and began spontaneous contraction at 3.0 ± 0.6 Hz at 15–21 days after the start of differentiation. CM had clear sarcomeric striations when stained for β-myosin heavy chain, and showed expression and punctate membrane localization of gap junction protein Connexin43. Calcium and voltage-sensitive imaging showed both action potential and calcium transients typical of immature CM. This study showed that the cardiac differentiation of pluripotent stem cells can be directed by porous silica vectors with temporally controlled release of small-molecule inhibitors. These results suggest methods for automating and eliminating variability in manual maintenance of inhibitor concentrations in the differentiation of pluripotent stem cells to CM.
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Enhancing Vascularization through the Controlled Release of Platelet-Derived Growth Factor-BB
ACS Applied Materials and Interfaces
The use of delivery systems to control the in vivo release of growth factors (GFs) for tissue engineering applications is extremely desirable. However, the clinical use of GFs is limited by their higher costs, associated with their fast in vivo turnover. Hence, the development of efficient and effective delivery systems, able to achieve the in vivo spatiotemporal control over the release of GFs, remains a challenge. Herein, we investigated the ability of multiscale composite micro-spheres…
The use of delivery systems to control the in vivo release of growth factors (GFs) for tissue engineering applications is extremely desirable. However, the clinical use of GFs is limited by their higher costs, associated with their fast in vivo turnover. Hence, the development of efficient and effective delivery systems, able to achieve the in vivo spatiotemporal control over the release of GFs, remains a challenge. Herein, we investigated the ability of multiscale composite micro-spheres, based on a nanostructured silicon multistage vector (MSV) core and a poly(DL-lactide-co-glycolide) acid (PLGA) outer shell (PLGA-MSV), to release functional platelet-derived growth factor-BB (PDGF-BB), to induce in vivo localized neo-vascularization. The in vitro release of PDGF-BB was assessed by enzyme-linked immunosorbent assay (ELISA) over 2 weeks, and showed a sustained almost zero-order release kinetic. The ability to promote in vivo localized neovascularization was investigated in a subcutaneous injection model in BALB/c mice, and followed by intravital mi-croscopy up to 2 weeks. Fully functional newly formed vessels were found solely within the area of tissue in which PLGA-MSVs were localized. This tissue was harvested and the distribution of CD31+ and α-SMA+ cells was detected by immunofluorescence. In addition, the tissue vascularization was also evaluated by histology. Finally, the level of up-regulation of angiogenesis-associated genes (Vegfa, Vwf, and Col3a1) was assessed by q-PCR, which showed a signifi-cantly higher level of expression in the site of injection of PLGA-MSVs. Altogether, our data supported the conclusion that the localized delivery of PDGF-BB from PLGA-MSVs induced the localized de-novo formation of fully functional vessels, in vivo. With this study, we demonstrated that PLGA-MSV holds promise for accomplishing the controlled localized in vivo release of GFs, for the design of innovative tissue engineering strategies.
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A nanofibrous electrospun patch to maintain human mesenchymal cell stemness
Journal of Materials Science: Materials in Medicine
Mesenchymal stem cells (MSCs) have been extensively investigated in regenerative medicine because of their crucial role in tissue healing. For these properties, they are widely tested in clinical trials, usually injected in cell suspension or in combination with tridimensional scaffolds. However, scaffolds can largely affect the fates of MSCs, inducing a progressive loss of functionality overtime. The ideal scaffold must delay MSCs differentiation until paracrine signals from the host induce…
Mesenchymal stem cells (MSCs) have been extensively investigated in regenerative medicine because of their crucial role in tissue healing. For these properties, they are widely tested in clinical trials, usually injected in cell suspension or in combination with tridimensional scaffolds. However, scaffolds can largely affect the fates of MSCs, inducing a progressive loss of functionality overtime. The ideal scaffold must delay MSCs differentiation until paracrine signals from the host induce their change. Herein, we proposed a nanostructured electrospun gelatin patch as an appropriate environment where human MSCs (hMSCs) can adhere, proliferate, and maintain their stemness. This patch exhibited characteristics of a non-linear elastic material and withstood degradation up to 4 weeks. As compared to culture and expansion in 2D, hMSCs on the patch showed a similar degree of proliferation and better maintained their progenitor properties, as assessed by their superior differentiation capacity towards typical mesenchymal lineages (i.e. osteogenic and chondrogenic). Furthermore, immunohistochemical analysis and longitudinal non-invasive imaging of inflammatory response revealed no sign of foreign body reaction for 3 weeks. In summary, our results demonstrated that our biocompatible patch favored the maintenance of undifferentiated hMSCs for up to 21 days and is an ideal candidate for tridimensional delivery of hMSCs. The present work reports a nanostructured patch gelatin-based able to maintain in vitro hMSCs stemness features. Moreover, hMSCs were able to differentiate toward osteo- and chondrogenic lineages once induces by differentiative media, confirming the ability of this patch to support stem cells for a potential in vivo application. These attractive properties together with the low inflammatory response in vivo make this patch a promising platform in regenerative medicine.
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Nanocomposite Hydrogels as Platform for Cells Growth, Proliferation, and Chemotaxis
Klein
The challenge of mimicking the extracellular matrix with artificial scaffolds that are able to reduce immunoresponse is still unmet. Recent findings have shown that mesenchymal stem cells (MSC) infiltrating into the implanted scaffold have effects on the implant integration by improving the healing process. Toward this aim, a novel polyamidoamine-based nanocomposite hydrogel is synthesized, cross-linked with porous nanomaterials (i.e., mesoporous silica nanoparticles), able to release chemokine…
The challenge of mimicking the extracellular matrix with artificial scaffolds that are able to reduce immunoresponse is still unmet. Recent findings have shown that mesenchymal stem cells (MSC) infiltrating into the implanted scaffold have effects on the implant integration by improving the healing process. Toward this aim, a novel polyamidoamine-based nanocomposite hydrogel is synthesized, cross-linked with porous nanomaterials (i.e., mesoporous silica nanoparticles), able to release chemokine proteins. A comprehensive viscoelasticity study confirms that the hydrogel provides optimal structural support for MSC infiltration and proliferation. The efficiency of this hydrogel, containing the chemoattractant stromal cell-derived factor 1α (SDF-1α), in promoting MSC migration in vitro is demonstrated. Finally, subcutaneous implantation of SDF-1α-releasing hydrogels in mice results in a modulation of the inflammatory reaction. Overall, the proposed SDF-1α-nanocomposite hydrogel proves to have potential for applications in tissue engineering.
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Patterning Biomaterials for the Spatiotemporal Delivery of Bioactive Molecules
Frontiers in Bioengineering and Biotechnology
The aim of tissue engineering is to promote the repair of functional tissues. For decades, the combined use of biomaterials, growth factors (GFs), and stem cells has been the base of several regeneration strategies. Among these, biomimicry emerged as a robust strategy to efficiently address this clinical challenge. Biomimetic materials, able to recapitulate the composition and architecture of the extracellular matrix, are the materials of choice, for their biocompatibility and higher rate of…
The aim of tissue engineering is to promote the repair of functional tissues. For decades, the combined use of biomaterials, growth factors (GFs), and stem cells has been the base of several regeneration strategies. Among these, biomimicry emerged as a robust strategy to efficiently address this clinical challenge. Biomimetic materials, able to recapitulate the composition and architecture of the extracellular matrix, are the materials of choice, for their biocompatibility and higher rate of efficacy. In addition, it has become increasingly clear that restoring the complex biochemical environment of the target tissue is crucial for its regeneration. Toward this aim, the combination of scaffolds and GFs is required. The advent of nanotechnology significantly impacted the field of tissue engineering by providing new ways to reproduce the complex spatial and temporal biochemical patterns of tissues. This review will present the most recent approaches to finely control the spatiotemporal release of bioactive molecules for various tissue engineering applications.
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Composite microsphere-functionalized scaffold for the controlled release of small molecules in tissue engineering
Journal of Tissue Engineering
Current tissue engineering strategies focus on restoring damaged tissue architectures using biologically active scaffolds. The ideal scaffold would mimic the extracellular matrix of any tissue of interest, promoting cell proliferation and de novo extracellular matrix deposition. A plethora of techniques have been evaluated to engineer scaffolds for the controlled and targeted release of bioactive molecules to provide a functional structure for tissue growth and remodeling, as well as enhance…
Current tissue engineering strategies focus on restoring damaged tissue architectures using biologically active scaffolds. The ideal scaffold would mimic the extracellular matrix of any tissue of interest, promoting cell proliferation and de novo extracellular matrix deposition. A plethora of techniques have been evaluated to engineer scaffolds for the controlled and targeted release of bioactive molecules to provide a functional structure for tissue growth and remodeling, as well as enhance recruitment and proliferation of autologous cells within the implant. Recently, novel approaches using small molecules, instead of growth factors, have been exploited to regulate tissue regeneration. The use of small synthetic molecules could be very advantageous because of their stability, tunability, and low cost. Herein, we propose a chitosan–gelatin scaffold functionalized with composite microspheres consisting of mesoporous silicon microparticles
and poly(dl-lactic-co-glycolic acid) for the controlled release of sphingosine-1-phospate, a small molecule of interest. We characterized the platform with scanning electron microscopy, Fourier transform infrared spectroscopy, and confocal microscopy. Finally, the biocompatibility of this multiscale system was analyzed by culturing human mesenchymal stem cells onto the scaffold. The presented strategy establishes the basis of a versatile scaffold for the controlled release of
small molecules and for culturing mesenchymal stem cells for regenerative medicine applications. -
Strategic Approaches to Growth Factors Delivery for Regenerative Medicine
OMICS Group eBooks
Organs transplantation or implantation of synthetic devices is the currently available and most used methods to treat loss of tissues and organs in humans. However, there is a continue demanding of new solutions and approaches for tissues failure since the definitive solution is far to be achieved. For this reason, regenerative medicine and tissue engineering are becoming of great interest as the alternative strategy to repair or regenerate damaged tissue. Among different regenerative…
Organs transplantation or implantation of synthetic devices is the currently available and most used methods to treat loss of tissues and organs in humans. However, there is a continue demanding of new solutions and approaches for tissues failure since the definitive solution is far to be achieved. For this reason, regenerative medicine and tissue engineering are becoming of great interest as the alternative strategy to repair or regenerate damaged tissue. Among different regenerative strategies, the development of synthetic scaffolds able to induce tissue restoration has been widely explored. The main goal of this approach is to develop functionalized platforms releasing growth factors or bioactive molecules that can lead desired cell response in order to enhance and accelerated tissue healing. A plethora of materials natural, synthetic and hybrid have been exploited to develop an adequate system for the sustained and controlled release of regenerative signals for the specific application. Recently, available delivery systems have some drawbacks such as growth factors loss of bioactivity, limited control over administrated dose and non-targeted delivery. Thus, the field of drug delivery systems for tissue engineering is still investigating new approaches and with the support of materials science new smart solutions to overcome these limitations. This chapter discusses carrier-based growth factor delivery systems with a particular focus on materials engineering for bone and cartilage tissue regeneration.
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PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins
ACS applied Materials and Interfaces
In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based…
In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(DL-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV’s morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. PLGA-MSV’s biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo
release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the biocompati -
Enabling cytoplasmic delivery and organelle targeting by surface modification of nanocarriers
Nanomedicine
Nanocarriers are designed to specifically accumulate in diseased tissues. In this context, targeting of intracellular compartments was shown to enhance the efficacy of many drugs and to offer new and more effective therapeutic approaches. This is especially true for therapies based on biologicals that must be encapsulated to favor cell internalization, and to avoid intracellular endosomal sequestration and degradation of the payload. In this review, we discuss specific surface modifications…
Nanocarriers are designed to specifically accumulate in diseased tissues. In this context, targeting of intracellular compartments was shown to enhance the efficacy of many drugs and to offer new and more effective therapeutic approaches. This is especially true for therapies based on biologicals that must be encapsulated to favor cell internalization, and to avoid intracellular endosomal sequestration and degradation of the payload. In this review, we discuss specific surface modifications designed to achieve cell cytoplasm delivery and to improve targeting of major organelles; we also discuss the therapeutic applications of these approaches. Last, we describe some integrated strategies designed to sequentially overcome the biological barriers that separate the site of administration from the cell cytoplasm, which is the drug's site of action.
Auszeichnungen/Preise
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Nature Conference in Tissue Engineering and Regenerative Medicine - Poster Competition
Nature
3000 RMB Poster Travel Award
Poster title: "Orchestrating cell-fate through functionalized biomimetic patches" -
GEORGE AND ANGELINA KOSTAS CARDIOVASCULAR NANOMEDICINE ANNUAL INTERNATIONAL MEETING - Poster Competition
Houston Methodist
500$ Poster Travel Award
Poster title: "BIOMIMETIC ELECTROSPUN CARDIOPATCH FOR THE CONTROLLED RELEASE OF GROWTH FACTORS FOR CARDIOVASCULAR APPLICATIONS" -
MAPTA Winter Symposium - Poster Competition
Houston Methodist
500$ Poster Travel Award
Poster title: "Double controlled release of TGF-β with PLGA-Porous Silicon composite microspheres for regenerative medicine applications."
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NACDS TSE, Day 2 in action! A big thank you to our trade partners and associates for their valuable time and interest in meeting with us! #NACDSTSE…
NACDS TSE, Day 2 in action! A big thank you to our trade partners and associates for their valuable time and interest in meeting with us! #NACDSTSE…
Beliebt bei Laura Pandolfi, PhD, MBA
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𝗪𝗶𝗹𝗹 𝘆𝗼𝘂 𝗮𝘁𝘁𝗲𝗻𝗱 𝗖𝗣𝗛𝗜 𝗠𝗶𝗹𝗮𝗻 𝟮𝟬𝟮𝟰? 𝗟𝗲𝘁'𝘀 𝗽𝗹𝗮𝗻 𝗮 𝗺𝗲𝗲𝘁𝗶𝗻𝗴 📅 We will be at CPHI this year from Oct 8th to 10th…
𝗪𝗶𝗹𝗹 𝘆𝗼𝘂 𝗮𝘁𝘁𝗲𝗻𝗱 𝗖𝗣𝗛𝗜 𝗠𝗶𝗹𝗮𝗻 𝟮𝟬𝟮𝟰? 𝗟𝗲𝘁'𝘀 𝗽𝗹𝗮𝗻 𝗮 𝗺𝗲𝗲𝘁𝗶𝗻𝗴 📅 We will be at CPHI this year from Oct 8th to 10th…
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I wanted to add that I will also be making an appearance in NJ this year, so please do reach out if you are going to be attending, as it would be…
I wanted to add that I will also be making an appearance in NJ this year, so please do reach out if you are going to be attending, as it would be…
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AntoXa Corporation and SwiftPharma will present their work to develop and commercialize a plant-made antibody treatment for #ricin exposure to the…
AntoXa Corporation and SwiftPharma will present their work to develop and commercialize a plant-made antibody treatment for #ricin exposure to the…
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New Jersey to Pennsylvania ✈ Adare Pharma Solutions move its HQ to Pennsylvania thanks to Governor Josh Shapiro of Pennsylvania announcing the…
New Jersey to Pennsylvania ✈ Adare Pharma Solutions move its HQ to Pennsylvania thanks to Governor Josh Shapiro of Pennsylvania announcing the…
Beliebt bei Laura Pandolfi, PhD, MBA
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#NACDS kicks off this week! Looking forward to reconnecting with our trade partners and unveiling six new product introductions! Find us at booth…
#NACDS kicks off this week! Looking forward to reconnecting with our trade partners and unveiling six new product introductions! Find us at booth…
Beliebt bei Laura Pandolfi, PhD, MBA
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🎓 Exciting Milestone! 🎓Last week I completed the Master in Business Administration (MBA) Executive program at Trinity Business School! Achieving…
🎓 Exciting Milestone! 🎓Last week I completed the Master in Business Administration (MBA) Executive program at Trinity Business School! Achieving…
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Immuniverse is a great IHI project that aims to identify similarities between colitis and atopic dermatitis. #Immuniverse
Immuniverse is a great IHI project that aims to identify similarities between colitis and atopic dermatitis. #Immuniverse
Beliebt bei Laura Pandolfi, PhD, MBA
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📣 Did you know that 1 in 17 people will develop dysphagia in their lifetime? We've developed innovative dosage forms designed to make medications…
📣 Did you know that 1 in 17 people will develop dysphagia in their lifetime? We've developed innovative dosage forms designed to make medications…
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#NACDSTSE is right around the corner! We're delighted to unveil 6 new product introductions and can't wait to connect with our trade partners at the…
#NACDSTSE is right around the corner! We're delighted to unveil 6 new product introductions and can't wait to connect with our trade partners at the…
Beliebt bei Laura Pandolfi, PhD, MBA