ORCID Profile
0000-0003-2732-8164
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Publisher: IOP Publishing
Date: 09-04-2021
Abstract: It has long been proposed that recapitulating the extracellular matrix (ECM) of native human tissues in the laboratory may enhance the regenerative capacity of engineered scaffolds in-vivo . Organ- and tissue-derived decellularized ECM biomaterials have been widely used for tissue repair, especially due to their intrinsic biochemical cues that can facilitate repair and regeneration. The main purpose of this study was to synthesize a new photocrosslinkable human bone-derived ECM hydrogel for bioprinting of vascularized scaffolds. To that end, we demineralized and decellularized human bone fragments to obtain a bone matrix, which was further processed and functionalized with methacrylate groups to form a photocrosslinkable methacrylate bone ECM hydrogel— bone-derived biomaterial (BoneMA). The mechanical properties of BoneMA were tunable, with the elastic modulus increasing as a function of photocrosslinking time, while still retaining the nanoscale features of the polymer networks. The intrinsic cell-compatibility of the bone matrix ensured the synthesis of a highly cytocompatible hydrogel. The bioprinted BoneMA scaffolds supported vascularization of endothelial cells and within a day led to the formation of interconnected vascular networks. We propose that such a quick vascular network formation was due to the host of pro-angiogenic biomolecules present in the bone ECM matrix. Further, we also demonstrate the bioprintability of BoneMA in microdimensions as injectable ECM-based building blocks for microscale tissue engineering in a minimally invasive manner. We conclude that BoneMA may be a useful hydrogel system for tissue engineering and regenerative medicine.
Publisher: SAGE Publications
Date: 26-05-2021
DOI: 10.1177/00220345211016429
Abstract: Calcium silicate cements (CSCs) are the choice materials for vital pulp therapy because of their bioactive properties, promotion of pulp repair, and dentin bridge formation. Despite the significant progress made in understanding CSCs’ mechanisms of action, the key events that characterize the early interplay between CSC-dentin-pulp are still poorly understood. To address this gap, a microfluidic device, the “tooth-on-a-chip,” which was developed to emulate the biomaterial-dentin-pulp interface, was used to test 1) the effect of CSCs (ProRoot, Biodentine, and TheraCal) on the viability and proliferation of human dental pulp stem cells, 2) variations of pH, and 3) release within the pulp chamber of transforming growth factor–β (TGFβ) as a surrogate of the bioactive dentin matrix molecules. ProRoot significantly increased the extraction of TGFβ ( P 0.05) within 24 to 72 h and, along with Biodentine, induced higher cell proliferation ( P 0.05), while TheraCal decreased cell viability and provoked atypical changes in cell morphology. No correlation between TGFβ levels and pH was observed. Further, we established a biofilm of Streptococcus mutans on-chip to model the biomaterial-biofilm-dentin interface and conducted a live and dead assay to test the antimicrobial capability of ProRoot in real time. In conclusion, the device allows for direct characterization of the interaction of bioactive dental materials with the dentin-pulp complex on a model of restored tooth while enabling assessment of antibiofilm properties at the interface in real time that was previously unattainable.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9LC00915A
Abstract: The tooth-on-chip is a novel platform that emulates the interface between dental materials, tooth and the underlying dental pulp.
Publisher: SAGE Publications
Date: 20-08-2021
Publisher: Cold Spring Harbor Laboratory
Date: 06-04-2022
DOI: 10.1101/2022.04.05.487240
Abstract: Pericytes stabilize blood vessels and promote vascular barrier function. However, vessels subjected to pro-inflammatory conditions have impaired barrier function, which has been suggested to potentially expose perivascular cells to SARS-CoV-2. To test this hypothesis, we engineered pericyte-supported vascular capillaries on-a-chip, and determined that the extravasation and binding of spike protein (S1) on perivascular cells of inflamed vessels to be significantly higher that in healthy controls, indicating a potential target to understand COVID-19 vascular complications.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1TB01673C
Abstract: Bone-like scaffolds were developed using a facile microparticles-assisted nanoscale mineralization of human mesenchymal stem cell-laden hydrogels.
Publisher: Wiley
Date: 07-03-2023
Abstract: Bone autografts remain the gold standard for bone grafting surgeries despite having increased donor site morbidity and limited availability. Bone morphogenetic protein‐loaded grafts represent another successful commercial alternative. However, the therapeutic use of recombinant growth factors has been associated with significant adverse clinical outcomes. This highlights the need to develop biomaterials that closely approximate the structure and composition of bone autografts, which are inherently osteoinductive and biologically active with embedded living cells, without the need for added supplements. Here, injectable growth factor‐free bone‐like tissue constructs are developed, that closely approximate the cellular, structural, and chemical composition of bone autografts. It is demonstrated that these micro‐constructs are inherently osteogenic, and demonstrate the ability to stimulate mineralized tissue formation and regenerate bone in critical‐sized defects in‐vivo. Furthermore, the mechanisms that allow human mesenchymal stem cells (hMSCs) to be highly osteogenic in these constructs, despite the lack of osteoinductive supplements, are assessed, whereby Yes activated protein (YAP) nuclear localization and adenosine signaling appear to regulate osteogenic cell differentiation. The findings represent a step toward a new class of minimally invasive, injectable, and inherently osteoinductive scaffolds, which are regenerative by virtue of their ability to mimic the tissue cellular and extracellular microenvironment, thus showing promise for clinical applications in regenerative engineering.
Publisher: Cold Spring Harbor Laboratory
Date: 26-03-2020
DOI: 10.1101/2020.03.25.008813
Abstract: The objective of this study was to investigate the controlled release of two growth factors (BMP-2 and VEGF) as a treatment strategy for clinically challenging composite injuries, consisting of a segmental bone defect and volumetric muscle loss. This is the first investigation of dual growth factor delivery in a composite injury model using an injectable smart delivery system consisting of heparin microparticles and alginate gel. The loading efficiency of growth factors into these biomaterials was found to be %, revealing a strong affinity of VEGF and BMP-2 to heparin and alginate. The system could achieve simultaneous or sequential release of VEGF and BMP-2 by varying the loading strategy. Single growth factor delivery (VEGF or BMP-2 alone) significantly enhanced vascular growth in vitro . However, no synergistic effect was observed for dual growth factor (BMP-2 + VEGF) delivery. Effective bone healing was achieved in all treatment groups (BMP-2, simultaneous or sequential delivery of BMP-2 and VEGF) in the composite injury model. The mechanics of the regenerated bone reached a maximum strength of ∼52% of intact bone with sequential delivery of VEGF and BMP-2. Overall, simultaneous or sequential co-delivery of low-dose BMP-2 and VEGF failed to fully restore the mechanics of bone in this injury model. Given the severity of the composite injury, VEGF alone may not be sufficient to establish mature and stable blood vessels when compared with previous studies co-delivering BMP-2+VEGF enhanced bone tissue regeneration. Hence, future studies are warranted to develop an alternative treatment strategy focusing on better control over growth factor dose, spatiotemporal delivery, and additional growth factors to regenerate fully functional bone tissue. We developed a smart growth factor delivery system using heparin microparticles and alginate that facilitates tunable delivery of VEGF and BMP-2 in a simultaneous or sequential manner by merely varying the loading strategy. In vitro , both VEGF and BMP-2 alone promoted vascular growth however, VEGF was significantly more potent, and there was no detectable benefit of co-delivery. In vivo , both BMP-2 alone and co-delivery of VEGF and BMP-2 promoted bone formation in the challenging bone/muscle polytrauma model however, none of the treatment groups restored biomechanical properties to that of uninjured bone.
Publisher: Wiley
Date: 23-07-2020
Publisher: Wiley
Date: 31-05-2023
Abstract: Successful integration of cell‐laden tissue constructs with host vasculature depends on the presence of functional capillaries to provide oxygen and nutrients to the embedded cells. However, diffusion limitations of cell‐laden biomaterials challenge regeneration of large tissue defects that require bulk‐delivery of hydrogels and cells. Here, a strategy to bioprint geometrically controlled, endothelial and stem‐cell laden microgels in high‐throughput is introduced, allowing these cells to form mature and functional pericyte‐supported vascular capillaries in vitro, and then injecting these pre‐vascularized constructs minimally invasively in‐vivo. It is demonstrated that this approach offers both desired scalability for translational applications as well as unprecedented levels of control over multiple microgel parameters to design spatially‐tailored microenvironments for better scaffold functionality and vasculature formation. As a proof‐of‐concept, the regenerative capacity of the bioprinted pre‐vascularized microgels is compared with that of cell‐laden monolithic hydrogels of the same cellular and matrix composition in hard‐to‐heal defects in vivo. The results demonstrate that the bioprinted microgels have faster and higher connective tissue formation, more vessels per area, and widespread presence of functional chimeric (human and murine) vascular capillaries across regenerated sites. The proposed strategy, therefore, addresses a significant issue in regenerative medicine, demonstrating a superior potential to facilitate translational regenerative efforts.
Publisher: American Chemical Society (ACS)
Date: 08-06-2018
Publisher: Wiley
Date: 05-11-2022
Abstract: Bioprinting has emerged as one of the most promising strategies for fabrication of functional organs in the lab as an alternative to transplant organs. While progress in the field has mostly been restricted to a few miniaturized tissues with minimal biological functionality until a few years ago, recent progress has advanced the concept of building three‐dimensional multicellular organ complexity remarkably. This review discusses a series of milestones that have paved the way for bioprinting of tissue constructs that have advanced levels of biological and architectural functionality. Critical materials, engineering and biological challenges that are key to addressing the desirable function of engineered organs are presented. These are discussed in light of the many difficulties to replicate the heterotypic organization of multicellular solid organs, the nanoscale precision of the extracellular microenvironment in hierarchical tissues, as well as the advantages and limitations of existing bioprinting methods to adequately overcome these barriers. In summary, the advances of the field toward realistic manufacturing of functional organs have never been so extensive, and this manuscript serves as a road map for some of the recent progress and the challenges ahead.
Publisher: Elsevier BV
Date: 2020
Publisher: Cold Spring Harbor Laboratory
Date: 28-08-2019
DOI: 10.1101/748053
Abstract: The tooth has a unique configuration with respect to biomaterials that are used for its treatment. Cells inside of the dental pulp interface indirectly with biomaterials via a calcified permeable membrane, formed by a dentin barrier which is composed of several thousands of dentinal tubules (~2 µm in diameter) connecting the dental pulp tissue to the outer surface of the tooth. Although the cytotoxic response of the dental pulp to biomaterials has been extensively studied, there is a shortage of in vitro model systems that mimic the dentin-pulp interface, enabling an improved understanding of the morphologic, metabolic and functional influence of biomaterials on live dental pulp cells. To address this shortage, here we developed an organ-on-a-chip model system which integrates cells cultured directly on a dentin wall within a microdevice which replicates some of the architecture and dynamics of the dentin-pulp interface. The tooth-on-a-chip is made out of molded polydimethylsiloxane (PDMS) with a design consisting of two chambers separated by a dentin fragment. To characterize pulp cell responses to dental materials on-chip, stem cell-derived odontoblasts were seeded onto the dentin surface, and observed using live-cell microscopy. Standard dental materials used clinically (2-hydroxyethylmethacrylate - HEMA, Phosphoric Acid - PA, and Adper-Scotchbond - SB) were tested for cytotoxicity, cell morphology and metabolic activity on-chip, and compared against standardized off-chip controls. All dental materials had cytotoxic effects in both on-chip and off-chip systems in the following order: HEMA SB PA (p .05), and cells presented consistently higher metabolic activity on-chip than off-chip (p .05). Furthermore, the tooth-on-a-chip enabled real-time tracking of odontoblast monolayer formation, remodeling, and death in response to biomaterial treatments, and gelatinolytic activity in a model hybrid layer (HL) formed in the microdevice. In conclusion, the tooth-on-a-chip is a novel platform that replicates near-physiologic conditions of the pulp-dentin interface, and enables live-cell imaging to study dental pulp cell response to biomaterials.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0LC00280A
Abstract: We proposed a novel concept for reconfiguration of hydrogel microfluidic devices, where multiple fluidic pathways could be generated via reversible manipulation of magnetic inks.
Publisher: IOP Publishing
Date: 10-01-2018
Publisher: Cold Spring Harbor Laboratory
Date: 04-03-2020
DOI: 10.1101/2020.03.02.974063
Abstract: It has long been proposed that recapitulating the extracellular matrix (ECM) of native human tissues in the laboratory may enhance the regenerative capacity of engineered scaffolds in-vivo. Organ- and tissue-derived decellularized ECM biomaterials have been widely used for tissue repair, especially due to their intrinsic biochemical cues that can facilitate repair and regeneration. The main purpose of this study was to synthesize a new photocrosslinkable human bone-derived ECM hydrogel for bioprinting of vascularized scaffolds. To that end, we demineralized and decellularized human bone fragments to obtain a bone matrix, which was further processed and functionalized with methacrylate groups to form a photocrosslinkable methacrylate bone ECM hydrogel – BoneMA. The mechanical properties of BoneMA were tunable, with the elastic modulus increasing as a function of photocrosslinking time, while still retaining the nanoscale features of the polymer networks. The intrinsic cell-compatibility of the bone matrix ensured the synthesis of a highly cytocompatible hydrogel. The bioprinted BoneMA scaffolds supported vascularization of endothelial cells and within a day led to the formation of interconnected vascular networks. We propose that such a quick vascular network formation was due to the host of pro-angiogenic biomolecules present in the bone ECM matrix. Further, we also demonstrate the bioprintability of BoneMA in microdimensions as injectable ECM-based building blocks for microscale tissue engineering in a minimally invasive manner. We conclude that BoneMA may be a useful hydrogel system for tissue engineering and regenerative medicine.
Publisher: Wiley
Date: 25-10-2020
Location: No location found
No related grants have been discovered for Luiz Bertassoni.