ORCID Profile
0000-0001-6433-8535
Current Organisation
North Dakota State University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
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: 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: 24-10-2019
Abstract: Providing appropriate biophysical and biochemical cues to the interface is a facile strategy to enhance the osteogenic ability of metallic implants. Here we exploited this through the incorporation of mesoporous bioactive glass nanoparticles (MBGN) at a high content (1:1 by weight) to a biopolymer chitosan in the electrodeposition process of titanium. The MGBN/chitosan layer thickness, tunable by electrodeposition parameters, exhibited an accelerated ability of apatite mineral induction in a body simulating medium. Of note, the involvement of MBGN could generate nanoscale roughness in a unique range of 10-25 nm. Moreover, the layer showed a slowly releasing profile of ions (calcium and silicate) over weeks at therapeutically relevant doses. The ion-releasing nanotopological surface was demonstrated to alter the preosteoblasts responses in a way favorable for osteogenic differentiation. The combinatory cues of nanotopology (25 nm roughness) and ion release enabled highly accelerated cellular anchorage with somewhat limited spreading area at initial periods. The subsequent osteoblastic differentiation behaviors on the engineered surface, as examined up to 21 days, showed significantly enhanced alkaline phosphate activity and up-regulated expression of bone-associated genes (ALP, Col I, OPN, and OCN). These results indicate that the combinatory cues provided by nanotopology (25 nm roughness) and ions released from MBGN are highly effective in stimulating osteoblastic differentiation and suggest that the MBGN/chitosan may serve as a potential composition for bone implant coatings.
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: American Chemical Society (ACS)
Date: 12-12-2018
Abstract: In the field of nanomedicine, drug-loaded nanocarriers that integrate nanotechnology and chemotherapeutics are widely used to achieve synergistic therapeutic effects. Here, we prepared mesoporous silica nanoparticles capped with cerium oxide nanoparticles (COP@MSN) wherein a pH trigger-responsive mechanism was used to control drug release and intracellular drug delivery. We blocked the mesopores of the carboxyl-functionalized MSN with aminated COP. These pores could be opened in acidic conditions to release the loaded drug, thus establishing a pH-responsive drug release system. We loaded doxorubicin (DOX) as anticancer biomolecule into the pores of MSN and capped with COP. The COP@DOX-MSN system showed a typical drug release profile in an acidic medium, which, however, was not observed in a neutral medium. In vitro studies using cancer cell line (HeLa) proved that the COP@DOX-MSN entered efficiently into HeLa cells and released DOX to the level sufficient for cytotoxicity. The cytotoxic effect of COP in cancer cells was facilitated by the pro-oxidant property of COPs, which considerably raised the reactive oxygen species (ROS) level, thereby leading to cellular apoptosis. The combination of DOX with COP (COP@DOX-MSN) showed even higher ROS level, demonstrating a cytotoxic synergism of drug and nanoparticle in terms of ROS generation. Collectively, the COP@DOX-MSN is considered useful for cancer treatment with the combined capacity of pH-controlled drug delivery, chemotherapeutics, and redox activity.
No related grants have been discovered for Prakash Parthiban Selvakumar.