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  • Effect of Plasma Treatment and Its Post Process Duration on Shear Bonding Strength and Antibacterial Effect of Dental Zirconia. Materials (Basel, Switzerland) Park, C., Park, S., Yun, K., Ji, M., Kim, S., Yang, Y. P., Lim, H. 2018; 11 (11)

    Abstract

    We have investigated the effect of non-thermal atmospheric pressure plasma (NTAPP) treatment and the post process time on the bonding strength and surface sterilization of dental zirconia. Presintered zirconia specimens were manufactured as discs, and then subjected to a 30-min argon treatment (Ar, 99.999%; 10 L/min) using an NTAPP device. Five post-treatment durations were evaluated: control (no treatment), P0 (immediate), P1 (24 h), P2 (48 h), and P3 (72 h). The surface characteristics, shear bonding strength (SBS) with two resin cements, and Streptococcus mutans biofilm formation of these plasma-treated dental zirconia were tested. Plasma did not change the roughness, and caused surface element changes and surface energy increase. Due to this increase in surface energy, SBS increased significantly (p < 0.05) within 48 h when RelyXTM U200 was used. However, the increase of surface oxygen significantly decreased (p < 0.05) the SBS of Panavia F 2.0 when using plasma immediately (P0). S. mutans adhesion decreased significantly (p < 0.05) for the P0, P1, and P2 groups compared to the control. The P0 group exhibited lower biofilm thickness than the other experimental groups due to the increased hydrophilicity (p < 0.05). Our study suggests that there is a suitable time window for the post NTAPP treatment regarding bonding strength and antimicrobial growth persist.

    View details for PubMedID 30423984

  • Effect of electron beam sterilization on 3D printed PCL/beta-TCP scaffolds for bone tissue engineering. Tissue engineering. Part A Bruyas, A., Moeinzadeh, S., Kim, S., Lowenberg, D. W., Yang, Y. P. 2018

    Abstract

    3D printing of composite materials such as polycaprolactone/beta-tricalcium phosphate (PCL/beta-TCP) enables the design and manufacturing of scaffolds with advanced geometries, along with improved physical and biological properties for large bone defect repair. Terminal sterilization of the scaffolds is inevitable for clinical applications. Electron beam (E-beam) is non-toxic, and can be used for sterilizing heat sensitive scaffolds by the use of high radiation dose in a short period of time. In this paper, we assessed the influence of E-beam sterilization on the properties of 3D printed PCL/beta-TCP scaffolds, focusing on the key physical and biological properties for bone tissue engineering. More specifically, we characterized the effect of a single dose E-beam sterilization (25kGy, ISO 11137) on surface morphology, hydrophilicity, degradation and mechanical properties of the scaffolds as well as in vitro biological responses. The results showed that E-beam irradiation did not alter the surface properties of scaffolds. A 14% increase in initial mechanical stiffness and strength of the scaffolds was observed after E-beam treatment. In addition, the E-beam treated scaffolds had 25% faster degradation. The PCL chains within the scaffolds had larger polydispersity after the E-beam irradiation that was indicative of a concurrent crosslinking and chain scission. Moreover, in vitro cell studies showed no influence of E-beam sterilization on viability, attachment, proliferation, and osteogenic differentiation of cells seeded on the PCL/beta-TCP scaffolds.

    View details for PubMedID 30234441

  • Functionally Graded, Bone- and Tendon-Like Polyurethane for Rotator Cuff Repair ADVANCED FUNCTIONAL MATERIALS Ker, D., Wang, D., Behn, A., Wang, E., Zhang, X., Zhou, B., Mercado-Pagan, A., Kim, S., Kleimeyer, J., Gharaibeh, B., Shanjani, Y., Nelson, D., Safran, M., Cheung, E., Campbell, P., Yang, Y. 2018; 28 (20)

    Abstract

    Critical considerations in engineering biomaterials for rotator cuff repair include bone-tendon-like mechanical properties to support physiological loading and biophysicochemical attributes that stabilize the repair site over the long-term. In this study, UV-crosslinkable polyurethane based on quadrol (Q), hexamethylene diisocyante (H), and methacrylic anhydride (M; QHM polymers), which are free of solvent, catalyst, and photoinitiator, is developed. Mechanical characterization studies demonstrate that QHM polymers possesses phototunable bone- and tendon-like tensile and compressive properties (12-74 MPa tensile strength, 0.6-2.7 GPa tensile modulus, 58-121 MPa compressive strength, and 1.5-3.0 GPa compressive modulus), including the capability to withstand 10 000 cycles of physiological tensile loading and reduce stress concentrations via stiffness gradients. Biophysicochemical studies demonstrate that QHM polymers have clinically favorable attributes vital to rotator cuff repair stability, including slow degradation profiles (5-30% mass loss after 8 weeks) with little-to-no cytotoxicity in vitro, exceptional suture retention ex vivo (2.79-3.56-fold less suture migration relative to a clinically available graft), and competent tensile properties (similar ultimate load but higher normalized tensile stiffness relative to a clinically available graft) as well as good biocompatibility for augmenting rat supraspinatus tendon repair in vivo. This work demonstrates functionally graded, bone-tendon-like biomaterials for interfacial tissue engineering.

    View details for PubMedID 29785178

  • Functional Outcomes of Heparin-Binding Epidermal Growth Factor-Like Growth Factor for Regeneration of Chronic Tympanic Membrane Perforations in Mice TISSUE ENGINEERING PART A Maria, P. L., Gottlieb, P., Maria, C. S., Kim, S., Puria, S., Yang, Y. P. 2017; 23 (9-10): 436-444

    Abstract

    We aim to demonstrate that regeneration of chronic tympanic perforations with heparin-binding epidermal growth factor-like growth factor (HB-EGF) delivered by an injectable hydrogel restored hearing to levels similar to that of nonperforated tympanic membranes. Chronic tympanic membrane perforation is currently managed as an outpatient surgery with tympanoplasty. Due to the costs of this procedure in the developed world and a lack of accessibility and resources in developing countries, there is a great need for a new treatment that does not require surgery. In this study, we show in a mouse model through measurement of auditory brainstem response and distortion product otoacoustic emissions that tympanic perforations lead to hearing loss and this can be predominantly recovered with HB-EGF treatment (5??g/mL). Our animal model suggests a return to function between 2 and 6 months after treatment. Auditory brainstem response thresholds had returned to the control levels at 2 months, but the distortion product otoacoustic emissions returned between 2 and 6 months. We also show how the vibration characteristics of the regenerated tympanic membrane, as measured by laser Doppler vibrometry, can be similar to that of an unperforated tympanic membrane. Using the best available methods for preclinical evaluation in animal models, it is likely that HB-EGF-like growth factor treatment leads to regeneration of chronic tympanic membrane perforations and restoration of the tympanic membrane to normal function, suggesting a potential route for nonsurgical treatment.

    View details for DOI 10.1089/ten.tea.2016.0395

    View details for Web of Science ID 000401342400007

  • Functional Outcomes of Heparin Binding - Epidermal Growth Factor Like Growth Factor for Regeneration of Chronic Tympanic Membrane Perforations in Mice. Tissue engineering. Part A Santa Maria, P. L., Gotlieb, P., Santa Maria, C., Puria, S., Kim, S., Yang, Y. P. 2017

    Abstract

    We aim to demonstrate that regeneration of chronic tympanic perforations with heparin-binding epidermal growth factor-like growth factor (HB-EGF) delivered by an injectable hydrogel restored hearing to levels similar to that of nonperforated tympanic membranes. Chronic tympanic membrane perforation is currently managed as an outpatient surgery with tympanoplasty. Due to the costs of this procedure in the developed world and a lack of accessibility and resources in developing countries, there is a great need for a new treatment that does not require surgery. In this study, we show in a mouse model through measurement of auditory brainstem response and distortion product otoacoustic emissions that tympanic perforations lead to hearing loss and this can be predominantly recovered with HB-EGF treatment (5??g/mL). Our animal model suggests a return to function between 2 and 6 months after treatment. Auditory brainstem response thresholds had returned to the control levels at 2 months, but the distortion product otoacoustic emissions returned between 2 and 6 months. We also show how the vibration characteristics of the regenerated tympanic membrane, as measured by laser Doppler vibrometry, can be similar to that of an unperforated tympanic membrane. Using the best available methods for preclinical evaluation in animal models, it is likely that HB-EGF-like growth factor treatment leads to regeneration of chronic tympanic membrane perforations and restoration of the tympanic membrane to normal function, suggesting a potential route for nonsurgical treatment.

    View details for DOI 10.1089/ten.TEA.2016.0395

    View details for PubMedID 28142401

  • Single Administration of a Sustained-Release Formulation of KB-R7785 Inhibits Tympanic Membrane Regeneration in an Animal Model JOURNAL OF INTERNATIONAL ADVANCED OTOLOGY Maria, P. L., Maria, C. S., Kim, S., Yang, Y. P. 2016; 12 (3): 237-240

    Abstract

    A pressure equalization tube placed within the tympanic membrane is the only clinically available method for inhibiting tympanic membrane regeneration. Problems associated with this include associated otorrhea, biofilm formation, medial migration of the tube, tube retention, induction of granulation tissue, and a small but significant rate of cholesteatoma. We aimed to demonstrate that a single administration of a sustained-release polymer formulation of KB-R7785 maintains tympanic membrane perforation for at least 6 months.Sustained-release KB-R7785 was delivered within a novel polymer hydrogel to 20 mice with bilateral acute tympanic membrane perforations (a total of 40 perforations). The perforations were monitored at 3-month intervals until 9 months.At 3 months, 90% of perforations were open (n=36/40). At 6 months, 75% of perforations were open (total n=30/40). At 9 months, 22.5% of perforations were open (total n=6/40). The majority of tympanic membrane perforations (75%) were open (not healed) beyond 6 months and close (fully healed) prior to 9 months (77.5%). Once healed, tympanic membranes resembled their normal histological appearance.This study demonstrates that a single administration of a sustained-release polymer formulation of KB-R7785 inhibits tympanic membrane regeneration for 6-9 months.

    View details for DOI 10.5152/iao.2016.3124

    View details for PubMedID 28031154

  • Engineering a Dual-Layer Chitosan-Lactide Hydrogel To Create Endothelial Cell Aggregate-Induced Microvascular Networks In Vitro and Increase Blood Perfusion In Vivo ACS APPLIED MATERIALS & INTERFACES Kim, S., Kawai, T., Wang, D., Yang, Y. 2016; 8 (30): 19245-19255

    Abstract

    Here, we report the use of chemically cross-linked and photo-cross-linked hydrogels to engineer human umbilical vein endothelial cell (HUVEC) aggregate-induced microvascular networks to increase blood perfusion in vivo. First, we studied the effect of chemically cross-linked and photo-cross-linked chitosan-lactide hydrogels on stiffness, degradation rates, and HUVEC behaviors. The photo-cross-linked hydrogel was relatively stiff (E = ?15 kPa) and possessed more compact networks, denser surface texture, and lower enzymatic degradation rates than the relatively soft, chemically cross-linked hydrogel (E = ?2 kPa). While both hydrogels exhibited nontoxicity, the soft chemically cross-linked hydrogels expedited the formation of cell aggregates compared to the photo-cross-linked hydrogels. Cells on the less stiff, chemically cross-linked hydrogels expressed more matrix metalloproteinase (MMP) activity than the stiffer, photo-cross-linked hydrogel. This difference in MMP activity resulted in a more dramatic decrease in mechanical stiffness after 3 days of incubation for the chemically cross-linked hydrogel, as compared to the photo-cross-linked one. After determining the physical and biological properties of each hydrogel, we accordingly engineered a dual-layer hydrogel construct consisting of the relatively soft, chemically cross-linked hydrogel layer for HUVEC encapsulation, and the relatively stiff, acellular, photo-cross-linked hydrogel for retention of cell-laden microvasculature above. This dual-layer hydrogel construct enabled a lasting HUVEC aggregate-induced microvascular network due to the combination of stable substrate, enriched cell adhesion molecules, and extracellular matrix proteins. We tested the dual-layer hydrogel construct in a mouse model of hind-limb ischemia, where the HUVEC aggregate-induced microvascular networks significantly enhanced blood perfusion rate to ischemic legs and decreased tissue necrosis compared with both no treatment and nonaggregated HUVEC-loaded hydrogels within 2 weeks. This study suggests an effective means for regulating hydrogel properties to facilitate a stable, HUVEC aggregate-induced microvascular network for a variety of vascularized tissue applications.

    View details for DOI 10.1021/acsami.6b04431

    View details for Web of Science ID 000380968300009

    View details for PubMedID 27399928

  • In Response to the Letter to the Editor Regarding: Heparin Binding-Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice. Tissue engineering. Part A Santa Maria, P. L., Kim, S., Varsak, Y. K., Yang, Y. P. 2016; 22 (5-6): 570-571

    View details for DOI 10.1089/ten.TEA.2016.0059

    View details for PubMedID 26908042

  • Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model OTOLOGY & NEUROTOLOGY Maria, P. L., Weierich, K., Kim, S., Yang, Y. P. 2015; 36 (7): 1279-1283

    Abstract

    That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model.A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle.The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 ?g/ml, n = 18), FGF2 (100 ?g/ml, n = 19), and EGF (250 ?g/ml, n = 19). Perforations were inspected at 4 weeks.The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration.This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

    View details for DOI 10.1097/MAO.0000000000000795

    View details for Web of Science ID 000358409500021

  • Heparin Binding-Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice TISSUE ENGINEERING PART A Maria, P. L., Kim, S., Varsak, Y. K., Yang, Y. P. 2015; 21 (9-10): 1483-1494

    Abstract

    We aim to explore the role of epidermal growth factor (EGF) ligand shedding in tympanic membrane wound healing and to investigate the translation of its modulation in tissue engineering of chronic tympanic membrane perforations. Chronic suppurative otitis media (CSOM) is an infected chronic tympanic membrane perforation. Up to 200 million suffer from its associated hearing loss and it is the most common cause of pediatric hearing loss in developing countries. There is a need for nonsurgical treatment due to a worldwide lack of resources. In this study, we show that EGF ligand shedding is essential for tympanic membrane healing as it's inhibition, with KB-R7785, leads to chronic perforation in 87.9% (n=58) compared with 0% (n=20) of controls. We then show that heparin binding-EGF-like growth factor (5??g/mL), which acts to shed EGF ligands, can regenerate chronic perforations in mouse models with 92% (22 of 24) compared with 38% (10 of 26), also with eustachian tube occlusion with 94% (18 of 19) compared with 9% (2 of 23) and with CSOM 100% (16 of 16) compared with 41% (7 of 17). We also show the nonototoxicity of this treatment and its hydrogel delivery vehicle. This provides preliminary data for a clinical trial where it could be delivered by nonspecialist trained healthcare workers and fulfill the clinical need for a nonsurgical treatment for chronic tympanic membrane perforation and CSOM.

    View details for DOI 10.1089/ten.tea.2014.0474

    View details for Web of Science ID 000353952300002

    View details for PubMedID 25567607

    View details for PubMedCentralID PMC4426296

  • Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects ACTA BIOMATERIALIA Kim, S., Bedigrew, K., Guda, T., Maloney, W. J., Park, S., Wenke, J. C., Yang, Y. P. 2014; 10 (12): 5021-5033
  • Novel osteoinductive photo-cross-linkable chitosan-lactide-fibrinogen hydrogels enhance bone regeneration in critical size segmental bone defects. Acta biomaterialia Kim, S., Bedigrew, K., Guda, T., Maloney, W. J., Park, S., Wenke, J. C., Yang, Y. P. 2014; 10 (12): 5021-5033

    Abstract

    The purpose of this study was to develop and characterize a novel photo-cross-linkable chitosan-lactide-fibrinogen (CLF) hydrogel and evaluate the efficacy of bone morphogenetic protein-2 (BMP-2) containing a CLF hydrogel for osteogenesis in vitro and in vivo. We synthesized the CLF hydrogels and characterized their chemical structure, degradation rate, compressive modulus and in vitro BMP-2 release kinetics. We evaluated bioactivities of the BMP-2 containing CLF hydrogels (0, 50, 100 and 500ngml(-1)) in vitro using W-20-17 preosteoblast mouse bone marrow stromal cells and C2C12 mouse myoblast cells. The effect of BMP-2 containing CLF gels (0, 0.5, 1, 2 and 5?g) on bone formation was evaluated using rat critical size segmental bone defects for 4weeks. Fourier transform infrared spectroscopy spectra and scanning electron microscopy images showed chemical and structural changes by the addition of fibrinogen into the chitosan-lactide copolymer. The incorporation of fibrinogen molecules significantly increased the compressive modulus of the hydrogels. The in vitro BMP-2 release study showed initial burst releases from the CLF hydrogels followed by sustained releases, regardless of the concentration of the BMP-2 over 4weeks. Cells in all groups were viable in the presence of the hydrogels regardless of BMP-2 doses, indicating non-cytotoxicity of hydrogels. Alkaline phosphate activity and mineralization of cells exhibited dose dependence on BMP-2 containing CLF hydrogels. Radiography, microcomputed tomography and histology confirmed that the BMP-2 containing CLF hydrogels prompted neo-osteogenesis and accelerated healing of the defects in a dose-dependent manner. Thus the CLF hydrogel is a promising delivery system of growth factors for bone regeneration.

    View details for DOI 10.1016/j.actbio.2014.08.028

    View details for PubMedID 25174669

  • In vitro evaluation of photo-crosslinkable chitosan-lactide hydrogels for bone tissue engineering JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Kim, S., Kang, Y., Mercado-Pagan, A. E., Maloney, W. J., Yang, Y. 2014; 102 (7): 1393-1406
  • Osteogenic and angiogenic potentials of monocultured and co-cultured human-bone-marrow-derived mesenchymal stem cells and human-umbilical-vein endothelial cells on three-dimensional porous beta-tricalcium phosphate scaffold ACTA BIOMATERIALIA Kang, Y., Kim, S., Fahrenholtz, M., Khademhosseini, A., Yang, Y. 2013; 9 (1): 4906-4915

    Abstract

    The use of biodegradable beta-tricalcium phosphate (?-TCP) scaffolds holds great promise for bone tissue engineering. However, the effects of ?-TCP on bone and endothelial cells are not fully understood. This study aimed to investigate cell proliferation and differentiation of mono- or co-cultured human-bone-marrow-derived mesenchymal stem cells (hBMSCs) and human-umbilical-vein endothelial cells (HUVECs) on a three-dimensional porous, biodegradable ?-TCP scaffold. In co-culture studies, the ratios of hBMSCs:HUVECs were 5:1, 1:1 and 1:5. Cellular morphologies of HUVECs, hBMSCs and co-cultured HUVECs/hBMSCs on the ?-TCP scaffolds were monitored using confocal and scanning electron microscopy. Cell proliferation was monitored by measuring the amount of double-stranded DNA (dsDNA) whereas hBMSC and HUVEC differentiation was assessed using the osteogenic and angiogenic markers, alkaline phosphatase (ALP) and PECAM-1 (CD31), respectively. Results show that HUVECs, hBMSCs and hBMSCs/HUVECs adhered to and proliferated well on the ?-TCP scaffolds. In monoculture, hBMSCs grew faster than HUVECs on the ?-TCP scaffolds after 7 days, but HUVECs reached similar levels of proliferation after 14 days. In monoculture, ?-TCP scaffolds promoted ALP activities of both hBMSCs and HUVECs when compared to those grown on tissue culture well plates. ALP activity of cells in co-culture was higher than that of hBMSCs in monoculture. Real-time polymerase chain reaction results indicate that runx2 and alp gene expression in monocultured hBMSCs remained unchanged at days 7 and 14, but alp gene expression was significantly increased in hBMSC co-cultures when the contribution of individual cell types was not distinguished.

    View details for DOI 10.1016/j.actbio.2012.08.008

    View details for Web of Science ID 000313376900047

    View details for PubMedID 22902820

    View details for PubMedCentralID PMC3508299

  • The osteogenic differentiation of human bone marrow MSCs on HUVEC-derived ECM and beta-TCP scaffold BIOMATERIALS Kang, Y., Kim, S., Bishop, J., Khademhosseini, A., Yang, Y. 2012; 33 (29): 6998-7007

    Abstract

    Extracellular matrix (ECM) serves a key role in cell migration, attachment, and cell development. Here we report that ECM derived from human umbilical vein endothelial cells (HUVEC) promoted osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSC). We first produced an HUVEC-derived ECM on a three-dimensional (3D) beta-tricalcium phosphate (?-TCP) scaffold by HUVEC seeding, incubation, and decellularization. The HUVEC-derived ECM was then characterized by SEM, FTIR, XPS, and immunofluorescence staining. The effect of HUVEC-derived ECM-containing ?-TCP scaffold on hMSC osteogenic differentiation was subsequently examined. SEM images indicate a dense matrix layer deposited on the surface of struts and pore walls. FTIR and XPS measurements show the presence of new functional groups (amide and hydroxyl groups) and elements (C and N) in the ECM/?-TCP scaffold when compared to the ?-TCP scaffold alone. Immunofluorescence images indicate that high levels of fibronectin and collagen IV and low level of laminin were present on the scaffold. ECM-containing ?-TCP scaffolds significantly increased alkaline phosphatase (ALP) specific activity and up-regulated expression of osteogenesis-related genes such as runx2, alkaline phosphatase, osteopontin and osteocalcin in hMSC, compared to ?-TCP scaffolds alone. This increased effect was due to the activation of MAPK/ERK signaling pathway since disruption of this pathway using an ERK inhibitor PD98059 results in down-regulation of these osteogenic genes. Cell-derived ECM-containing calcium phosphate scaffolds is a promising osteogenic-promoting bone void filler in bone tissue regeneration.

    View details for DOI 10.1016/j.biomaterials.2012.06.061

    View details for Web of Science ID 000308269600010

    View details for PubMedID 22795852

    View details for PubMedCentralID PMC3427692

  • Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation ACTA BIOMATERIALIA Kim, S., Kang, Y., Krueger, C. A., Sen, M., Holcomb, J. B., Chen, D., Wenke, J. C., Yang, Y. 2012; 8 (5): 1768-1777

    Abstract

    The purpose of this study was to develop and characterize a chitosan gel/gelatin microsphere (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1-containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system compared with other treatments (P<0.05) after a week of culture.

    View details for DOI 10.1016/j.actbio.2012.01.009

    View details for Web of Science ID 000302989700012

    View details for PubMedID 22293583

    View details for PubMedCentralID PMC3314097

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