Khandmaa Dashnyam
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Khandmaa Dashnyam has a total of 68 co-authors. Here are the top co-authors by number of shared publications:
- Jung-Hwan Lee
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
8 shared publications - Hae-Hyoung Lee
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
5 shared publications - Hae-Won Kim
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea
5 shared publications - Jeong-Hui Park
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandaero, Cheonan 31116, Republic of Korea
5 shared publications - Jonathan Campbell Knowles
UCL Eastman Dental Institute
5 shared publications - Soo-Kyung Jun
Department of Biomaterials Science, College of Dentistry, Dankook University, 119 Dandaero, Cheonan 31116, Republic of Korea
4 shared publications
Latest Publications
- 18 March 2026
- Published by Springer Nature in Infection
Integrating machine learning and artificial intelligence in the management of Acinetobacter infections: a narrative review
Acinetobacter baumannii, particularly in its multidrug-resistant (MDR) and carbapenem-resistant (CRAB) forms, has become a major global health concern due to its ability to survive in hospital environments, acquire resistance rapidly, and cause severe infections with high mortality. Conventional diagnostic and therapeutic strategies remain slow, imprecise, and difficult to implement, especially in resource-limited settings, highlighting the need for innovative approaches. Advances in artificial intelligence (AI) and machine learning (ML) offer powerful tools to strengthen every stage of Acinetobacter infection management. This narrative review synthesizes current evidence on how AI enhances early detection, improves species-level identification, predicts antimicrobial resistance from genomic data, accelerates drug discovery, and supports real-time hospital surveillance and outbreak control. AI-driven methods enable faster triage, more accurate differentiation between colonization and true infection, robust prediction of resistance phenotypes, and efficient identification of synergistic antibiotic combinations. Moreover, AI-supported drug discovery pipelines have recently yielded novel agents such as abaucin, demonstrating the potential of computational approaches to explore new chemical spaces. Despite these promising advances, challenges persist regarding data quality, generalizability across settings, interpretability, and ethical considerations including privacy and algorithmic bias. Successful integration of AI into clinical practice will require rigorous model validation, equitable data governance, and strong collaboration between clinicians, microbiologists, and data scientists. Overall, AI represents a transformative opportunity to reduce the clinical and economic burden of Acinetobacter infections and to strengthen global antimicrobial resistance surveillance.
- 18 March 2026
- Published by Springer Nature in Infection
Integrating machine learning and artificial intelligence in the management of Acinetobacter infections: a narrative review
Acinetobacter baumannii, particularly in its multidrug-resistant (MDR) and carbapenem-resistant (CRAB) forms, has become a major global health concern due to its ability to survive in hospital environments, acquire resistance rapidly, and cause severe infections with high mortality. Conventional diagnostic and therapeutic strategies remain slow, imprecise, and difficult to implement, especially in resource-limited settings, highlighting the need for innovative approaches. Advances in artificial intelligence (AI) and machine learning (ML) offer powerful tools to strengthen every stage of Acinetobacter infection management. This narrative review synthesizes current evidence on how AI enhances early detection, improves species-level identification, predicts antimicrobial resistance from genomic data, accelerates drug discovery, and supports real-time hospital surveillance and outbreak control. AI-driven methods enable faster triage, more accurate differentiation between colonization and true infection, robust prediction of resistance phenotypes, and efficient identification of synergistic antibiotic combinations. Moreover, AI-supported drug discovery pipelines have recently yielded novel agents such as abaucin, demonstrating the potential of computational approaches to explore new chemical spaces. Despite these promising advances, challenges persist regarding data quality, generalizability across settings, interpretability, and ethical considerations including privacy and algorithmic bias. Successful integration of AI into clinical practice will require rigorous model validation, equitable data governance, and strong collaboration between clinicians, microbiologists, and data scientists. Overall, AI represents a transformative opportunity to reduce the clinical and economic burden of Acinetobacter infections and to strengthen global antimicrobial resistance surveillance.
- 22 April 2025
- Published by Sciencedomain International in Journal of Pharmaceutical Research International
- Vol. 37 (5) , 133-147
Rapid Lymphatic Absorption of Orally Administered Low-Molecular-Weight Hyaluronic Acid: A Pathway to the Bloodstream via Mesenteric Nodes
Background: The 35 kDa low-molecular-weight hyaluronic acid (HA35) injection has shown efficacy in alleviating various types of pain, reducing inflammation and edema, and exhibiting potential in lipolysis and cosmetic applications. Compared to injectable forms, oral administration offers greater convenience and improved patient compliance. However, the absorption mechanism of orally administered low-molecular-weight hyaluronic acid (LMWHA, 1000 kDa), which requires degradation prior to absorption, this study demonstrates for the first time that LMWHA molecules (HA35 and HA70, <100 kDa) can be directly absorbed through the intestinal lymphatic system. This alternative absorption route is significant, as it enables compounds to bypass hepatic first-pass metabolism, potentially enhancing bioavailability and prolonging systemic exposure. These findings provide new insights into the absorption mechanisms of LMWHA and suggest promising opportunities for developing oral therapeutics that leverage lymphatic transport pathways for the improved delivery of bioactive macromolecules.
- 22 April 2025
- Published by Sciencedomain International in Journal of Pharmaceutical Research International
- Vol. 37 (5) , 133-147
Rapid Lymphatic Absorption of Orally Administered Low-Molecular-Weight Hyaluronic Acid: A Pathway to the Bloodstream via Mesenteric Nodes
Background: The 35 kDa low-molecular-weight hyaluronic acid (HA35) injection has shown efficacy in alleviating various types of pain, reducing inflammation and edema, and exhibiting potential in lipolysis and cosmetic applications. Compared to injectable forms, oral administration offers greater convenience and improved patient compliance. However, the absorption mechanism of orally administered low-molecular-weight hyaluronic acid (LMWHA, 1000 kDa), which requires degradation prior to absorption, this study demonstrates for the first time that LMWHA molecules (HA35 and HA70, <100 kDa) can be directly absorbed through the intestinal lymphatic system. This alternative absorption route is significant, as it enables compounds to bypass hepatic first-pass metabolism, potentially enhancing bioavailability and prolonging systemic exposure. These findings provide new insights into the absorption mechanisms of LMWHA and suggest promising opportunities for developing oral therapeutics that leverage lymphatic transport pathways for the improved delivery of bioactive macromolecules.
- Open Access
- 9 June 2023
- Published by MDPI AG in Pharmaceutics
- Vol. 15 (6) , 1701
Physicochemical, Biological, and Antibacterial Properties of Four Bioactive Calcium Silicate-Based Cements
Calcium silicate-based cement (CSC) is a pharmaceutical agent that is widely used in dentistry. This bioactive material is used for vital pulp treatment due to its excellent biocompatibility, sealing ability, and antibacterial activity. Its drawbacks include a long setting time and poor maneuverability. Hence, the clinical properties of CSC have recently been improved to decrease its setting time. Despite the widespread clinical usage of CSC, there is no research comparing recently developed CSCs. Therefore, the purpose of this study is to compare the physicochemical, biological, and antibacterial properties of four commercial CSCs: two powder–liquid mix types (RetroMTA® [RETM]; Endocem® MTA Zr [ECZR]) and two premixed types (Well-Root™ PT [WRPT]; Endocem® MTA premixed [ECPR]). Each sample was prepared using circular Teflon molds, and tests were conducted after 24 h of setting. The premixed CSCs exhibited a more uniform and less rough surface, higher flowability, and lower film thickness than the powder–liquid mix CSCs. In the pH test, all CSCs showed values between 11.5 and 12.5. In the biological test, cells exposed to ECZR at a concentration of 25% showed greater cell viability, but none of the samples showed a significant difference at low concentration (p > 0.05). Alkaline phosphatase staining revealed that cells exposed to ECZR underwent more odontoblast differentiation than the cells exposed to the other materials; however, no significant difference was observed at a concentration of 12.5% (p > 0.05). In the antibacterial test, the premixed CSCs showed better results than the powder–liquid mix CSCs, and ECPR yielded the best results, followed by WRPT. In conclusion, the premixed CSCs showed improved physical properties, and of the premixed types, ECPR exhibited the highest antibacterial properties. For biological properties, none of these materials showed significant differences at 12.5% dilution. Therefore, ECPR may be a promising material with high antibacterial activity among the four CSCs, but further investigation is needed for clinical situations.
- 9 June 2023
- Published by MDPI AG in Pharmaceutics
- Vol. 15 (6) , 1701
Open AccessPhysicochemical, Biological, and Antibacterial Properties of Four Bioactive Calcium Silicate-Based Cements
Calcium silicate-based cement (CSC) is a pharmaceutical agent that is widely used in dentistry. This bioactive material is used for vital pulp treatment due to its excellent biocompatibility, sealing ability, and antibacterial activity. Its drawbacks include a long setting time and poor maneuverability. Hence, the clinical properties of CSC have recently been improved to decrease its setting time. Despite the widespread clinical usage of CSC, there is no research comparing recently developed CSCs. Therefore, the purpose of this study is to compare the physicochemical, biological, and antibacterial properties of four commercial CSCs: two powder–liquid mix types (RetroMTA® [RETM]; Endocem® MTA Zr [ECZR]) and two premixed types (Well-Root™ PT [WRPT]; Endocem® MTA premixed [ECPR]). Each sample was prepared using circular Teflon molds, and tests were conducted after 24 h of setting. The premixed CSCs exhibited a more uniform and less rough surface, higher flowability, and lower film thickness than the powder–liquid mix CSCs. In the pH test, all CSCs showed values between 11.5 and 12.5. In the biological test, cells exposed to ECZR at a concentration of 25% showed greater cell viability, but none of the samples showed a significant difference at low concentration (p > 0.05). Alkaline phosphatase staining revealed that cells exposed to ECZR underwent more odontoblast differentiation than the cells exposed to the other materials; however, no significant difference was observed at a concentration of 12.5% (p > 0.05). In the antibacterial test, the premixed CSCs showed better results than the powder–liquid mix CSCs, and ECPR yielded the best results, followed by WRPT. In conclusion, the premixed CSCs showed improved physical properties, and of the premixed types, ECPR exhibited the highest antibacterial properties. For biological properties, none of these materials showed significant differences at 12.5% dilution. Therefore, ECPR may be a promising material with high antibacterial activity among the four CSCs, but further investigation is needed for clinical situations.
- Open Access
- 27 March 2023
- Published by MDPI AG in Pharmaceutics
- Vol. 15 (4) , 1072
Physicochemical, Pre-Clinical, and Biological Evaluation of Viscosity Optimized Sodium Iodide-Incorporated Paste
This study aimed to investigate the impact of different viscosities of silicone oil on the physicochemical, pre-clinical usability, and biological properties of a sodium iodide paste. Six different paste groups were created by mixing therapeutic molecules, sodium iodide (D30) and iodoform (I30), with calcium hydroxide and one of the three different viscosities of silicone oil (high (H), medium (M), and low (L)). The study evaluated the performance of these groups, including I30H, I30M, I30L, D30H, D30M, and D30L, using multiple parameters such as flow, film thickness, pH, viscosity, and injectability, with statistical analysis (p < 0.05). Remarkably, the D30L group demonstrated superior outcomes compared to the conventional iodoform counterpart, including a significant reduction in osteoclast formation, as examined through TRAP, c-FOS, NFATc1, and Cathepsin K (p < 0.05). Additionally, mRNA sequencing showed that the I30L group exhibited increased expression of inflammatory genes with upregulated cytokines compared to the D30L group. These findings suggest that the optimized viscosity of the sodium iodide paste (D30L) may lead to clinically favorable outcomes, such as slower root resorption, when used in primary teeth. Overall, the results of this study suggest that the D30L group shows the most satisfactory outcomes, which may be a promising root-filling material that could replace conventional iodoform-based pastes.
- 27 March 2023
- Published by MDPI AG in Pharmaceutics
- Vol. 15 (4) , 1072
Open AccessPhysicochemical, Pre-Clinical, and Biological Evaluation of Viscosity Optimized Sodium Iodide-Incorporated Paste
This study aimed to investigate the impact of different viscosities of silicone oil on the physicochemical, pre-clinical usability, and biological properties of a sodium iodide paste. Six different paste groups were created by mixing therapeutic molecules, sodium iodide (D30) and iodoform (I30), with calcium hydroxide and one of the three different viscosities of silicone oil (high (H), medium (M), and low (L)). The study evaluated the performance of these groups, including I30H, I30M, I30L, D30H, D30M, and D30L, using multiple parameters such as flow, film thickness, pH, viscosity, and injectability, with statistical analysis (p < 0.05). Remarkably, the D30L group demonstrated superior outcomes compared to the conventional iodoform counterpart, including a significant reduction in osteoclast formation, as examined through TRAP, c-FOS, NFATc1, and Cathepsin K (p < 0.05). Additionally, mRNA sequencing showed that the I30L group exhibited increased expression of inflammatory genes with upregulated cytokines compared to the D30L group. These findings suggest that the optimized viscosity of the sodium iodide paste (D30L) may lead to clinically favorable outcomes, such as slower root resorption, when used in primary teeth. Overall, the results of this study suggest that the D30L group shows the most satisfactory outcomes, which may be a promising root-filling material that could replace conventional iodoform-based pastes.
- Open Access
- 28 September 2022
- Published by Royal Society of Chemistry (RSC) in RSC Advances
- Vol. 12 (43) , 27963-27969
One-pot synthesis and enzyme-responsiveness of amphiphilic doxorubicin prodrug nanomicelles for cancer therapeutics
A doxorubicin-based nanomedicine with a one-pot synthesis method and FDA-approved materials could solve the problems of a complicated preparation process and avoid the use of non-FDA-approved materials for clinical use and industrial production.
- 28 September 2022
- Published by Royal Society of Chemistry (RSC) in RSC Advances
- Vol. 12 (43) , 27963-27969
Open AccessOne-pot synthesis and enzyme-responsiveness of amphiphilic doxorubicin prodrug nanomicelles for cancer therapeutics
A doxorubicin-based nanomedicine with a one-pot synthesis method and FDA-approved materials could solve the problems of a complicated preparation process and avoid the use of non-FDA-approved materials for clinical use and industrial production.
- Open Access
- 8 September 2022
- Published by MDPI AG in Pharmaceutics
- Vol. 14 (9) , 1903
Premixed Calcium Silicate-Based Root Canal Sealer Reinforced with Bioactive Glass Nanoparticles to Improve Biological Properties
Recently, bioactive glass nanoparticles (BGns) have been acknowledged for their ability to promote interactions with the periapical tissue and enhance tissue regeneration by releasing therapeutic ions. However, there have been no studies on calcium silicate sealers with bioactive glass nanoparticle (BGn) additives. In the present study, a premixed calcium silicate root canal sealer reinforced with BGn (pre-mixed-RCS@BGn) was developed and its physicochemical features and biological effects were analyzed. Three specimens were in the trial: 0%, 0.5%, and 1% bioactive glass nanoparticles (BGns) were gradually added to the premixed type of calcium silicate-based sealer (pre-mixed-RCS). To elucidate the surface properties, scanning electron microscopy, X-ray diffraction, and energy-dispersive spectroscopy were used and flowability, setting time, solubility, and radiopacity were analyzed to evaluate the physical properties. Chemical properties were investigated by water contact angle, pH change, and ion release measurements. The antibacterial effects of the bioactive set sealers were tested with Enterococcus faecalis and the viability of human bone marrow-derived mesenchymal stem cells (hMSCs) with this biomaterial was examined. In addition, osteogenic differentiation was highly stimulated, which was confirmed by ALP (Alkaline phosphatase) activity and the ARS (Alizarin red S) staining of hMSCs. The pre-mixed-RCS@BGn satisfied the ISO standards for root canal sealers and maintained antimicrobial activity. Moreover, pre-mixed-RCS@BGn with more BGns turned out to have less cytotoxicity than pre-mixed-RCS without BGns while promoting osteogenic differentiation, mainly due to calcium and silicon ion release. Our results suggest that BGns enhance the biological properties of this calcium silicate-based sealer and that the newly introduced pre-mixed-RCS@BGn has the capability to be applied in dental procedures as a root canal sealer. Further studies focusing more on the biocompatibility of pre-mixed-RCS@BGn should be performed to investigate in vivo systems, including pulp tissue.
- 8 September 2022
- Published by MDPI AG in Pharmaceutics
- Vol. 14 (9) , 1903
Open AccessPremixed Calcium Silicate-Based Root Canal Sealer Reinforced with Bioactive Glass Nanoparticles to Improve Biological Properties
Recently, bioactive glass nanoparticles (BGns) have been acknowledged for their ability to promote interactions with the periapical tissue and enhance tissue regeneration by releasing therapeutic ions. However, there have been no studies on calcium silicate sealers with bioactive glass nanoparticle (BGn) additives. In the present study, a premixed calcium silicate root canal sealer reinforced with BGn (pre-mixed-RCS@BGn) was developed and its physicochemical features and biological effects were analyzed. Three specimens were in the trial: 0%, 0.5%, and 1% bioactive glass nanoparticles (BGns) were gradually added to the premixed type of calcium silicate-based sealer (pre-mixed-RCS). To elucidate the surface properties, scanning electron microscopy, X-ray diffraction, and energy-dispersive spectroscopy were used and flowability, setting time, solubility, and radiopacity were analyzed to evaluate the physical properties. Chemical properties were investigated by water contact angle, pH change, and ion release measurements. The antibacterial effects of the bioactive set sealers were tested with Enterococcus faecalis and the viability of human bone marrow-derived mesenchymal stem cells (hMSCs) with this biomaterial was examined. In addition, osteogenic differentiation was highly stimulated, which was confirmed by ALP (Alkaline phosphatase) activity and the ARS (Alizarin red S) staining of hMSCs. The pre-mixed-RCS@BGn satisfied the ISO standards for root canal sealers and maintained antimicrobial activity. Moreover, pre-mixed-RCS@BGn with more BGns turned out to have less cytotoxicity than pre-mixed-RCS without BGns while promoting osteogenic differentiation, mainly due to calcium and silicon ion release. Our results suggest that BGns enhance the biological properties of this calcium silicate-based sealer and that the newly introduced pre-mixed-RCS@BGn has the capability to be applied in dental procedures as a root canal sealer. Further studies focusing more on the biocompatibility of pre-mixed-RCS@BGn should be performed to investigate in vivo systems, including pulp tissue.
- Open Access
- 15 April 2022
- Published by MDPI AG in Biomedicines
- Vol. 10 (4) , 906
Investigating the Effects of Conditioned Media from Stem Cells of Human Exfoliated Deciduous Teeth on Dental Pulp Stem Cells
Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have been considered a promising tool for regenerative therapy due to their ability to secrete multiple factors that are essential for tissue regeneration, which is achieved by minimally invasive procedures with fewer ethical or legal concerns than those of other procedures. The aim of this study is to investigate the potency of SHED-derived conditioned media (SHED CM) on dental pulp stem cells (DPSCs), a major type of mesenchymal stem cells for dental pulp regeneration. Our results show the promotive efficiency of SHED CM on the proliferation, survival rate, and migration of DPSCs in a dose-dependent manner. Upregulation of odontoblast/osteogenic-related marker genes, such as ALP, DSPP, DMP1, OCN, and RUNX2, and enhanced mineral deposition of impaired DPSCs are also observed in the presence of SHED CM. The analysis of SHED CM found that a variety of cytokines and growth factors have positive effects on cell proliferation, migration, anti-apoptosis, and odontoblast/osteogenic differentiation. These findings suggest that SHED CM could provide some benefits to DPSCs in pulp regeneration.
- 15 April 2022
- Published by MDPI AG in Biomedicines
- Vol. 10 (4) , 906
Open AccessInvestigating the Effects of Conditioned Media from Stem Cells of Human Exfoliated Deciduous Teeth on Dental Pulp Stem Cells
Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have been considered a promising tool for regenerative therapy due to their ability to secrete multiple factors that are essential for tissue regeneration, which is achieved by minimally invasive procedures with fewer ethical or legal concerns than those of other procedures. The aim of this study is to investigate the potency of SHED-derived conditioned media (SHED CM) on dental pulp stem cells (DPSCs), a major type of mesenchymal stem cells for dental pulp regeneration. Our results show the promotive efficiency of SHED CM on the proliferation, survival rate, and migration of DPSCs in a dose-dependent manner. Upregulation of odontoblast/osteogenic-related marker genes, such as ALP, DSPP, DMP1, OCN, and RUNX2, and enhanced mineral deposition of impaired DPSCs are also observed in the presence of SHED CM. The analysis of SHED CM found that a variety of cytokines and growth factors have positive effects on cell proliferation, migration, anti-apoptosis, and odontoblast/osteogenic differentiation. These findings suggest that SHED CM could provide some benefits to DPSCs in pulp regeneration.
- 1 February 2022
- Published by Elsevier in Dental Materials
- Vol. 38 (2) , 363-375
Investigating the mechanophysical and biological characteristics of therapeutic dental cement incorporating copper doped bioglass nanoparticles
- 1 February 2022
- Published by Elsevier in Dental Materials
- Vol. 38 (2) , 363-375
Investigating the mechanophysical and biological characteristics of therapeutic dental cement incorporating copper doped bioglass nanoparticles
- 8 July 2020
- Published by American Chemical Society (ACS) in ACS Biomaterials Science & Engineering
- Vol. 6 (8) , 4604-4613
Nanoscale Calcium Salt-Based Formulations As Potential Therapeutics for Osteoporosis
Osteoporosis causes severe bone damage, posing potential risks to human health, patient quality of life, and society. Calcium has been widely studied to enhance bone density and prevent osteoporosis-related bone fractures. Here, we focused on the calcium salt and its possible therapeutic effect for osteoporosis. In particular, we developed a nanoscale calcium salt from a natural origin and formulated nanocomposite tablets with the addition of vitamin D, herb (Rhodiola rosea) and natural mineral substance (Shilajit), which are also known to be anti-osteoporotic. The calcium salt nanocomposites revealed no toxicity, and stimulated the osteogenic differentiation, in particular, for the formulation with R. rosea. The calcium salt nanocomposites inhibited the osteoclastic activity including RANKL expression by decreasing TRAP positive cells. When administered orally to an osteoporotic rat for 45 days, the calcium salt nanocomposites reduced bone resorption as evidenced by the significantly higher bone volume and density as well as the increased osteoblasts with reduced osteoclasts compared to the non-treated control. The systemic administration exhibited no severe stomach toxicity or damage and no renal stone growth over the test period. Based on the significant bilateral effects on the osteoblast stimulation and osteoclast inhibition, and the resultant efficacy in an osteoporotic model, the nanocomposite tablets composed of calcium salt and natural products are considered as novel nanotherapeutics for the osteoporosis treatment.
- 8 July 2020
- Published by American Chemical Society (ACS) in ACS Biomaterials Science & Engineering
- Vol. 6 (8) , 4604-4613
Nanoscale Calcium Salt-Based Formulations As Potential Therapeutics for Osteoporosis
Osteoporosis causes severe bone damage, posing potential risks to human health, patient quality of life, and society. Calcium has been widely studied to enhance bone density and prevent osteoporosis-related bone fractures. Here, we focused on the calcium salt and its possible therapeutic effect for osteoporosis. In particular, we developed a nanoscale calcium salt from a natural origin and formulated nanocomposite tablets with the addition of vitamin D, herb (Rhodiola rosea) and natural mineral substance (Shilajit), which are also known to be anti-osteoporotic. The calcium salt nanocomposites revealed no toxicity, and stimulated the osteogenic differentiation, in particular, for the formulation with R. rosea. The calcium salt nanocomposites inhibited the osteoclastic activity including RANKL expression by decreasing TRAP positive cells. When administered orally to an osteoporotic rat for 45 days, the calcium salt nanocomposites reduced bone resorption as evidenced by the significantly higher bone volume and density as well as the increased osteoblasts with reduced osteoclasts compared to the non-treated control. The systemic administration exhibited no severe stomach toxicity or damage and no renal stone growth over the test period. Based on the significant bilateral effects on the osteoblast stimulation and osteoclast inhibition, and the resultant efficacy in an osteoporotic model, the nanocomposite tablets composed of calcium salt and natural products are considered as novel nanotherapeutics for the osteoporosis treatment.
- 3 October 2019
- Published by Royal Society of Chemistry (RSC) in Biomaterials Science
- Vol. 7 (12) , 5221-5231
Angiogenesis-promoted bone repair with silicate-shelled hydrogel fiber scaffolds
Promoting angiogenesis is a key strategy for stimulating the repair of damaged tissues, including bone. Among other proangiogenic factors, ions have recently been considered a potent element that can be incorporated into biomaterials and then released at therapeutic doses. Silicate-based biomaterials have been reported to induce neovascularization through vascular endothelial growth factor signaling pathway, potentiating acceleration of bone regeneration. Here, we designed a silicate-shelled hydrogel fiber scaffold with a hard/soft layered structure to investigate the possibility of silicate coating on biopolymer for enhancing biological properties. An alginate hydrogel was injected to form a fiber scaffold with shape-tunability that was then coated with a thin silicate layer with various sol–gel compositions. The silicate/alginate scaffold could release calcium and silicate ions, and in particular, silicate ion release was highly sustainable for over one week at therapeutically relevant levels. The ionic release was highly effective in stimulating the mRNA expression of angiogenic markers (VEGF, KDR, eNOS, bFGF, and HIF1-α) in endothelial cells (HUVECs). Moreover, the in vitro tubular networking of cells was significantly enhanced (1.5 times). In vivo implantation in subcutaneous tissue revealed more pronounced blood vessel formation around the silicate-shelled scaffolds than around silicate-free scaffolds. The presence of a silicate shell was also shown to accelerate acellular mineral (hydroxyapatite) formation. The cellular osteogenesis potential of the silicate/alginate scaffold was further proven by the enhanced expression of osteogenic genes (Col1a1, ALP and OCN). When implanted in a rat calvarium defect, the silicate-shelled scaffold demonstrated significantly improved bone formation (2–3 times higher in bone volume and density) with a concurrent sign of proangiogenesis. This work highlights that the surface-layering of silicate composition is an effective approach for improving the bone regeneration capacity of polymeric hydrogel scaffolds by stimulating ion-induced angiogenesis and providing bone bioactivity to the surface.
- 3 October 2019
- Published by Royal Society of Chemistry (RSC) in Biomaterials Science
- Vol. 7 (12) , 5221-5231
Angiogenesis-promoted bone repair with silicate-shelled hydrogel fiber scaffolds
Promoting angiogenesis is a key strategy for stimulating the repair of damaged tissues, including bone. Among other proangiogenic factors, ions have recently been considered a potent element that can be incorporated into biomaterials and then released at therapeutic doses. Silicate-based biomaterials have been reported to induce neovascularization through vascular endothelial growth factor signaling pathway, potentiating acceleration of bone regeneration. Here, we designed a silicate-shelled hydrogel fiber scaffold with a hard/soft layered structure to investigate the possibility of silicate coating on biopolymer for enhancing biological properties. An alginate hydrogel was injected to form a fiber scaffold with shape-tunability that was then coated with a thin silicate layer with various sol–gel compositions. The silicate/alginate scaffold could release calcium and silicate ions, and in particular, silicate ion release was highly sustainable for over one week at therapeutically relevant levels. The ionic release was highly effective in stimulating the mRNA expression of angiogenic markers (VEGF, KDR, eNOS, bFGF, and HIF1-α) in endothelial cells (HUVECs). Moreover, the in vitro tubular networking of cells was significantly enhanced (1.5 times). In vivo implantation in subcutaneous tissue revealed more pronounced blood vessel formation around the silicate-shelled scaffolds than around silicate-free scaffolds. The presence of a silicate shell was also shown to accelerate acellular mineral (hydroxyapatite) formation. The cellular osteogenesis potential of the silicate/alginate scaffold was further proven by the enhanced expression of osteogenic genes (Col1a1, ALP and OCN). When implanted in a rat calvarium defect, the silicate-shelled scaffold demonstrated significantly improved bone formation (2–3 times higher in bone volume and density) with a concurrent sign of proangiogenesis. This work highlights that the surface-layering of silicate composition is an effective approach for improving the bone regeneration capacity of polymeric hydrogel scaffolds by stimulating ion-induced angiogenesis and providing bone bioactivity to the surface.