Biomedical subjects

Weiyuan John Kao

Publications and source records attributed to Weiyuan John Kao.

At least 19 recordsLinked to original sources

PubMed2006

Thermoresponsive gelatin/monomethoxy poly(ethylene glycol)-poly(D,L-lactide) hydrogels: formulation, characterization, and antibacterial drug delivery.

PURPOSE: The primary objective of this study was to prepare novel thermoresponsive binary component hydrogels composed of gelatin and monomethoxy poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PDLLA) diblock copolymer and to obtain optimal formulations capable of forming gels upon a narrow temperature range between body temperature and room temperature. METHODS: MPEG-PDLLA diblock copolymers with a lower critical solution temperature (LCST) feature were synthesized by using a ring-opening polymerization method. The starting weight ratio of MPEG/DLLA was varied to obtain a series of copolymers with a wide range of molecular weight and hydrophilicity. The copolymers were characterized by 1H nuclear magnetic resonance (1H NMR) and thermogravimetric analysis. MPEG (2K)-PDLLA (1:4) was chosen to construct hydrogels with gelatin. To obtain optimal thermoresponsive formulation, various hydrogels were formulated and quantified in terms of sol-gel phase transition kinetics and rheological properties. Selected hydrogels were studied as drug carrier for gentamicin sulfate. RESULTS: Gelatin/MPEG-PDLLA hydrogels underwent gelation in less than 15 min when 30 wt.% MPEG (2K)-PDLLA (1:4) was mixed with 10, 50, or 100 mg/mL gelatin. Hydrogels showed rapid gelation when 100 mg/mL gelatin was mixed with 15, 20, or 25 wt.% MPEG-PDLLA as temperature fell from 37 degrees C to room temperature. The viscosity of hydrogels depended on the frequency applied in the rheological tests, the environment temperature, and the concentration of both polymer components. The time needed for 50% gentamicin sulfate release was 5 days or longer at room temperature, and the release lasted up to 40 days. 1H NMR confirmed that MPEG-PDLLA hydrolyzed under in vitro situations. CONCLUSIONS: The incorporation of a second polymer component MPEG-PDLLA into the gelatin hydrogel could modify the thermal characteristic of gelatin and the resulting binary component hydrogels obtained different thermal characteristics from the individual polymer components. Formulation of gelatin/MPEG-PDLLA hydrogels could be varied for obtaining such gels that can undergo gelation promptly upon a narrow temperature change.

Anti-Bacterial Agents↗

PubMed2006

Macrophage matrix metalloproteinase-2/-9 gene and protein expression following adhesion to ECM-derived multifunctional matrices via integrin complexation.

Macrophages are commonly observed at the biomaterial-tissue interface and interact with the extracellular matrix (ECM) mainly by integrin receptors to play a critical role in ECM turnover by secreting matrix metalloproteinases (MMPs). To investigate beta1 and beta3 containing integrin-mediated adhesion and subsequent MMP-2/-9 protein and gene expression in human blood-derived monocytes, biofunctional peptides immobilized onto flexible polyethylene glycol (PEG) arms were grafted onto a gelatin-based interpenetrating network (IPN). Adherent monocyte density was dramatically greater in the presence of RGD immobilized onto flexible PEG arms of the gelatin-based IPN. Pretreatment of monocytes with either anti-integrin beta1 or beta3 led to a significant decrease in adherent cell density on RGD-PEG-grafted IPNs. MMP-2 and MMP-9 protein and MMP-9 mRNA expression increased in the presence of IPNs initially, independent of ligand identity. Anti-integrin beta1 or beta3 antibody pretreatment of monocytes led to a general decrease in MMP-2/-9 protein expression. These results demonstrate the importance of beta1 and beta3 containing integrins in mediating monocyte adhesion onto RGD immobilized onto flexible PEG arms of the IPN. The results also reveal that MMP-2/-9 protein and gene expression is influenced by the presence of gelatin and not the ligands immobilized on the PEG arms of the IPN.

Cell Adhesion↗

PubMed2006

The interrelated role of fibronectin and interleukin-1 in biomaterial-modulated macrophage function.

Macrophages play a critical role in mediating the host response to biomaterials, perhaps most notably by guiding the host inflammatory response through the release of inflammatory molecules such as the cytokine interleukin-1 (IL-1). The extent of the macrophage response following interaction with the biomaterial surface contributes greatly to device efficacy, yet the molecular mechanisms of this interaction are still unclear. The extracellular matrix (ECM) protein fibronectin (FN) is recognized by macrophages and frequently used in biomaterial modification to elicit greater cellular adhesion and tissue integration. Macrophage interaction with FN and other ECM molecules on the biomaterial surface has been shown to induce a variety of inflammatory responses, thus both FN and IL-1 can be utilized as model molecules to better understand the mechanisms of material-mediated macrophage responses. This literature review presents a comprehensive survey of past and current research on the interrelated role of IL-1, FN, and FN-derivatives in determining biomaterial-modulated macrophage function.

Animals↗

PubMed2006

Effect of surface-adsorbed proteins and phosphorylation inhibitor AG18 on intracellular protein expression in adherent macrophages.

Macrophages are believed to play an important role in the host inflammatory response to implanted biomaterials. However, the mechanism of macrophage adhesion to protein-adsorbed substrates and the subsequent activation and inflammation is unresolved. Previously the effect of various surface-adsorbed proteins and increasing concentrations of phosphorylation inhibitor AG18 on intracellular protein expression levels in adherent human monocytic cell line U937 was identified using SDS-PAGE and densitometry. The protein ligands and AG18 concentrations up or down regulated the expression of a set of proteins ranging from approximately 200 to approximately 23 kDa. In the present work, HPLC coupled tandem mass spectroscopy (LC/MS) was used to identify proteins in these bands. We hypothesized that key proteins in macrophage adhesion and activation could be identified by observing protein expression resulting from various surface-adsorbed ligands and AG18 concentrations. Increasing concentrations of AG18 down or up regulate protein expression in adherent U937 on PBS-adsorbed TCPS at approximately 52, approximately 42 and approximately 23 kDa. AG18 concentrations had no effect on cells on albumin (Alb)-adsorbed surfaces but regulated different protein expression in adherent U937 on fibronectin (FN)-adsorbed TCPS at 40 and 80 microm AG18. Both Alb and FN regulate distinct sets of proteins in adherent cells as surface-adsorbed ligands. Based on the data from LC/MS, both surface associated ligand and increasing concentrations of AG18 modulate shifts in intracellular signaling.

Adsorption↗

PubMed2006

Dendrimers for pharmaceutical and biomedical applications.

Dendrimers are a unique class of synthetic macromolecules having a highly branched, three-dimensional, nanoscale architecture with very low polydispersity and high functionality. Structural advantages allow dendrimers to play an important role in the fields of nanotechnology, pharmaceutical and medicinal chemistry. This review discusses several aspects of dendrimers, including preparation, dendrimer-drug coupling chemistry, structural models of dendrimer-based drug delivery systems, and physicochemical and toxicological properties.

Chemical Phenomena↗

PubMed2005

Intracellular protein phosphorylation in adherent U937 monocytes mediated by various culture conditions and fibronectin-derived surface ligands.

Macrophages play a central role in the normal healing process after tissue injury and the host response to foreign objects such as biomaterials. The process leading to macrophage adhesion and activation on protein-adsorbed substrates is complex and unresolved. While the use of primary cells offers clinical relevancy, macrophage cell lines offer unique advantages such as availability and relatively homogeneous phenotype as models to probe the molecular mechanism of cell-surface interaction. Our goal was to better characterize the effect of the culture condition and surface-associated ligands on the extent of U937 adhesion. Tyrosine phosphorylation of intracellular proteins was surveyed as a basis to seek a greater understanding of the molecular mechanism involved in mediating U937 adhesion on various ligand-adsorbed surfaces. U937 viability and adhesion on tissue culture polystyrene (TCPS) increased with (i) increasing serum level, (ii) decreasing tyrosine phosphorylation inhibitor AG18 concentration, or (iii) increasing culture time. The adsorption of various adhesion proteins such as fibronectin and peptide ligands (i.e., RGD, PHSRN) on TCPS did not significantly increase the adherent density of U937 when compared with albumin and PBS ligand controls. However, ligand identity and the presence of phorbol myristate acetate dramatically affected the extent (i.e., increase or decrease) and the identity (i.e., molecular weight) of phosphotyrosine proteins in adherent U937 in a time-dependent manner. The extent and identity of phosphotyrosine proteins did not exhibit a clear AG18 dose dependency, rather the level of tyrosine phosphorylation for a distinct group of proteins was either increased or decreased for a given AG18 concentration.

Antineoplastic Agents↗

PubMed2005

Keratinocyte-fibroblast paracrine interaction: the effects of substrate and culture condition.

Interactions between epidermal-dermal cells via soluble factors provide important signals in regulating the reepithelialization of wounded skin. For example, keratinocytes regulate the expression of keratinocyte growth factor (KGF) in fibroblasts through the release of interleukin-1beta (IL-1beta). In this study, a previously developed polyethyleneglycol-based interpenetrating network (IPN) system was utilized as a platform for the delivery of keratinocyte-active factors. The effect of substrate chemistry, culture condition, and the delivery of exogenous keratinocyte-active factors on the keratinocyte behavior and the keratinocyte-fibroblast paracrine relationship was delineated. Adherent keratinocyte density on TCPS and glutaraldehyde-fixed gelatin hydrogels but not on IPN was significantly increased with culture time in the presence of growth supplements independent of the released KGF from the gelatin hydrogel and IPN. In the presence of fibroblasts, adherent keratinocyte density on gelatin hydrogels was higher than that without fibroblasts. This phenomenon was not observed on IPN and polycarbonate membrane. In summary, the delivered exogenous huKGF (i.e., released from a biomaterial matrix) operates in tandem with fibroblasts in regulating keratinocyte activation (i.e., IL-lbeta release and adhesion) in a surface-dependent manner. Immunoassay analysis of cell culture keratinocyte-fibroblast paracrine relationship as characterized by IL-1beta and KGF could not be established in the presence of IPNs, 0.1% glutaraldehyde-fixed gelatin hydrogels, and polycarbonate membranes.

Cell Adhesion↗

PubMed2005

Tensile creep properties of interpenetrating networks containing gelatin and poly(ethylene glycol) diacrylate.

The tensile creep properties of an interpenetrating networks (IPN) system containing polyanionic ethylenediaminetetraacetic dianhydride (EDTAD)-modified gelatin and poly(ethylene glycol) diacrylate (PEGdA) of 600 or 2000 Da at various weight ratios were determined under different pH and load levels. A computerized creep testing device was designed following ASTM D2990 and validated to establish the environment-dependent structure-function relationship of IPNs. IPNs containing PEGdA 2000 Da or EDTAD-modified gelatin showed less strain than those formulated with PEGdA 600 Da or unmodified gelatin, respectively. IPN formulated with 40 wt% gelatin showed higher strain than those with 50 or 30 wt% gelatin. Increasing strain in IPN was observed with increasing load level. IPN strain was higher at pH 7 when compared to pH 4 or 10. The creep characteristics of this complex macromolecular system are dependent on both environmental and composition factors.

Anhydrides↗

PubMed2004

Analysis of poly(ethylene glycol)-diacrylate macromer polymerization within a multicomponent semi-interpenetrating polymer network system.

Semi-interpenetrating polymer networks (semi-IPNs) containing poly(ethylene glycol)-diacrylate (PEGdA) and modified gelatin were prepared with 2,2-dimethoxy-2-phenylacetophenone (DMPA) as a photoinitiator. The effect of (i) initiator and PEGdA concentration, and (ii) weight ratio and type of modified gelatin on the conversion of PEGdA functional end groups was monitored in situ using attenuated total reflectance-Fourier transform infrared (ATR-FTIR). Reaction induction time was dependent on DMPA concentration and increased with decreasing DMPA concentration. Relative reaction rate was strongly dependent on both DMPA and PEGdA concentrations. Gelatin weight ratio and modification did not significantly affect reaction induction time, relative reaction rate, or reaction end time. Swelling/degradation kinetics at various aqueous conditions sought to establish relationships between diacrylate conversion and the resulting semi-IPN physical properties. Semi-IPN swelling weight ratio was strongly dependent on solvent conditions and semi-IPN exposure to gamma-irradiation. Gelatin backbone modification and UV exposure time exhibited no effect on semi-IPN swelling weight ratio. In conclusion, ATR-FTIR presents a viable means of monitoring the conversion of PEGdA functional end groups within a complex mixture. UV exposure >10 s did not significantly affect the weight swelling ratio, and supports our ATR-FTIR results that network formation reached completion before 3 min of UV exposure.

Acetophenones↗

PubMed2004

Tissue adhesiveness and host response of in situ photopolymerizable interpenetrating networks containing methylprednisolone acetate.

Interpenetrating networks (IPNs) of varying formulations were investigated as candidates for an in situ photopolymerizable drug delivery matrix containing poly(ethylene glycol) diacrylate and gelatin. The anti-inflammatory agent methylprednisolone acetate was loaded into the IPN. Bond strength between the IPN and tissue (i.e., muscle, dermis, skin) was determined by a modified American Society for Testing and Materials peel test at constant peel rate. The IPNs provided adhesion values of up to 5.7N, which were three- to fivefold lower than that of the commercial tissue bioadhesive. The subcutaneous cage implant system was utilized to assess material host response and drug efficacy in vivo. IPN formulations elicited a more intense acute inflammatory response than the empty cage controls. Methylprednisolone acetate loaded within the IPNs lowered the level of inflammatory response to levels that were comparable to the empty cage baseline controls. In conclusion, a methodology was developed to quantify the tissue adhesiveness of an in situ photopolymerized IPN matrix containing anti-inflammatory agents. The efficacy of drug-loaded IPN in affecting the host inflammatory response was demonstrated in vivo.

Biocompatible Materials↗

PubMed2003

Synthesis and physicochemical analysis of interpenetrating networks containing modified gelatin and poly(ethylene glycol) diacrylate.

The interrelated effects of gelatin modification, content, and poly(ethylene glycol) molecular weight on the melting temperature, surface hydrophilicity, tensile properties, swelling/degradation, and drug-release kinetics of a novel interpenetrating network (IPN) system containing gelatin and poly(ethylene glycol) diacrylate were evaluated. Gelatin content had a large effect on the IPN melting temperature and Delta H. Modifying gelatin with ethylenediaminetetraacetic acid and/or monomethoxy poly(ethylene glycol) monoacetate ester as well as increasing poly(ethylene glycol) diacrylate molecular weight increased the surface hydrophilicity. Increasing the gelatin weight percent increased the IPN elasticity at room temperature. When buffer and elevated temperature were present in the testing environment, the elasticity of all IPNs tested decreased. IPNs showed an enhanced elasticity and strength when compared with glutaraldehyde-fixed gelatin hydrogels. The extent of IPN swelling and degradation was increased by increasing the gelatin content or by modifying gelatin. The time to complete sample degradation was longer for IPNs when compared with gelatin crosslinked with glutaraldehyde. Modifications to the IPN system increased the maximum percent of chlorhexidine digluconate released from the IPNs. The rate of complete drug release was slower from IPNs than from glutaraldehyde-fixed gelatin matrices. A wide range of IPN physicochemical properties was obtained through formulation changes and chemical modifications.

Biocompatible Materials↗

PubMed2003

Synthesis and physicochemical analysis of gelatin-based hydrogels for drug carrier matrices.

This study examined the interrelated effect of environmental pH, gelatin backbone modification and crosslinking modality on hydrogel morphology, surface hydrophilicity, in vitro swelling/degradation kinetics, in vitro drug release kinetics and in vivo degradation, inflammatory response and drug release activity. The percent glutaraldehyde fixation had a greater impact on the morphology of the dehydrated hydrogels than gelatin modification. Any decrease in percent glutaraldehyde fixation and/or modification of gelatin with polyethylene glycol dialdehyde (PEG-dial) and/or ethylenediaminetetraacetic dianhydride (EDTAD) increased hydrogel surface hydrophilicity. Swelling/degradation studies showed that modification of gelatin with PEG-dial generally increased the time to reach the maximum swelling weight ratio (T(max)) and the time to failure by hydrolysis (T(fail)), but had little effect on the maximum swelling weight ratio (R(max)) and the weight ratio at failure (R(fail)). Modification of gelatin with EDTAD generally had no effect on T(max) and T(fail), but increased R(max) and R(fail). Modification of gelatin with PEG-dial and EDTAD increased R(max), but had no effect on T(max), R(fail), or T(fail). Decreasing percent glutaraldehyde fixation generally increased R(max) and R(fail) but decreased T(max) and T(fail). Decreasing environmental pH from 7.4 to 4.5 had no effect on any swelling/degradation properties. In vitro drug release studies showed that modification of gelatin with PEG-dial and/or EDTAD generally decreased the maximum mass ratio of drug released (D(max)) and the time to reach D(max) (T(dmax)). Percent glutaraldehyde fixation did not significantly affect D(max) or T(dmax) (except for EDTAD-modified gelatin hydrogels). In vivo studies showed that gelatin-based hydrogels elicited comparable levels of acute and chronic inflammatory response as that of the empty cage control by 21 d.

Biocompatible Materials↗

PubMed2003

Intracellular protein tyrosine phosphorylation of adherent human macrophages on adsorbed fibronectin.

Fibronectin (FN) was pre-adsorbed onto physicochemically distinct substrates: polyethyleneglycol-based networks or tissue culture polystyrene (TCPS). The role of these substrates in modulating FN-mediated intracellular protein tyrosine phosphorylation and cell adhesion was analyzed with human primary blood derived macrophages. Although macrophage adhesion on both FN-pre-adsorbed TCPS and networks was similarly dependent on protein tyrosine kinase (PTK) and protein serine/threonine kinase (PSK), the compensation between PTK and PSK, and the involvement of signaling molecules (such as protein kinase C (PKC) isoforms) were distinct between the substrates. The pattern and the extent of tyrosine phosphorylation of several proteins (i.e. approximately 70, approximately 44, approximately 30kDa) were differentially regulated by PKCs. FN-derived peptides were employed to probe this material-dependency in macrophage adhesion and tyrosine phosphorylation. The PHSRN domain in the peptide sequence was predominant in mediating this substrate-dependent FN signaling event. We conclude that the tyrosine phosphorylation and the cross talk between PTK and PSK are modulated by FN and the substrate onto which the protein is adsorbed.

Adsorption↗

PubMed2003

Cell interaction with protein-loaded interpenetrating networks containing modified gelatin and poly(ethylene glycol) diacrylate.

The effects of modification to an interpenetrating network (IPN) system composed of gelatin and poly(ethylene glycol) diacrylate were characterized by protein release kinetics, fibroblast adhesion, and in vivo host response. The maximum cumulative percent of parvalbumin released from various IPN formulations ranged from 17.6+/-3.2% to 56.9+/-35.4% over 2-96h. Despite modifying gelatin with ethylenediaminetetraacetic dianhydride and/or monomethoxy poly(ethylene glycol) monoacetate ester or increasing the gelatin content, the largest amount of parvalbumin released occurred within 24h, prior to material bulk degradation. Over the time period evaluated, little (i.e. <1%) of the basic fibroblast growth factor (bFGF) loaded into the IPNs evaluated was released, independent of modifications made to the IPN formulation. Fibroblast adhesion to IPNs with or without loaded bFGF was quantified. The adherent fibroblast density on the IPNs was significantly lower than that of TCPS controls at all times independent of the IPN formulation tested and bFGF loading. Select IPN formulations elicited a comparable level of acute and chronic inflammatory response in vivo when compared with the gelatin and poly(ethylene glycol) diacrylate starting materials. IPNs provide a minimal cell-active surface that could be employed as delivery matrices and for further bioconjugation to mediate specific cellular response.

Biocompatible Materials↗

PubMed2002

Intracellular signaling involved in macrophage adhesion and FBGC formation as mediated by ligand-substrate interaction.

Fibronectin and RGD- and/or PHSRN-containing oligopeptides were preadsorbed onto physicochemically distinct substrata: polyethyleneglycol-based networks or tissue culture polystyrene (TCPS). The role of selected signaling kinases (namely protein tyrosine kinases, protein serine/threonine kinases, PI3-kinase, Src, and MAPK) in the adhesion of human primary blood-derived macrophages and the formation of foreign-body giant cells (FBGC) on these modified substrata was investigated. The involvement of individual intracellular signaling molecules in mediating macrophage adhesion dynamically varied with the culture time, substrate, and ligand. For example, fibronectin on TCPS or networks involved similar signaling events for macrophage adhesion; however, fibronectin and G(3)RGDG(6)PHSRNG, but not peptides with other RGD and/or PHSRN orientations, mediated similar signaling events for macrophage adhesion on TCPS but mediated different signaling events on networks. Depending on the substrate, a specific molecule (i.e., Src, protein kinase C) within the protein tyrosine kinase or protein serine/threonine kinase family was either an antagonist or agonist in mediating FBGC formation.

Adsorption↗

PubMed2002

Engineering endogenous inflammatory cells as delivery vehicles.

Leukocytes are central in directing host inflammatory and immune processes; therefore, leukocyte response to biomaterials is extremely important. Although several leukocyte-derived molecules are used clinically, the long-term efficacy of treatments involving the systemic administration of these bioactive agents has yet to be demonstrated. Hence, the localized delivery of selected cytokines and growth factors produced by endogenous leukocytes is desirable and may have potential therapeutic values in the fundamental processes of tissue healing, growth regulation, and biocompatibility. The specificity and diversity of ligand-receptor interactions offer an attractive method in manipulating cellular behavior. Therefore, a more detailed understanding of the interplay between ligands and cell membrane receptors must be obtained. We designed interleukin-1-derived biomimetic agonists and antagonists to study and modulate leukocyte function in vitro. Selected agonists increased GM-CSF release by adherent human blood-derived macrophages in the presence of the natural IL1beta antagonist, namely IL1ra. Furthermore, IL1-derived biomimetic antagonists neutralized the ability of IL1beta in increasing the release of GM-CSF by adherent macrophages. We employed similar methodologies to elucidate the molecular mechanisms of integrin and extracellular matrix interaction in regulating leukocyte function. Oligopeptides were designed based on the functional structure of fibronectin and grafted on to a polymer network containing polyethyleneglycols. Macrophage adhesion was independent of the peptide identity that contained sequence RGD, PHSRN, PRRARV, or combinations thereof in an integrin-dependent fashion in vitro. However, integrin-dependent FBGC formation in vitro was highly dependent on both RGD and PHSRN in a single peptide formulation and with a specific orientation. From our intracellular signaling studies in vitro, protein tyrosine and serine/threonine kinases were found important in integrin signaling leading to macrophage adhesion mediated by fibronectin-integrin association. Furthermore, RGD and PHSRN appear to be significant in mediating this receptor-ligand association resulting in the necessary signaling characteristic for macrophage adhesion and the subsequent development. Our in vivo results showed that peptide identity played a minimal role in modulating the host inflammatory response and adherent macrophage density. RGD-containing peptides mediated rapid FBGC formation by 4 days of implantation by significantly increasing both the number of macrophages that participate in the cell fusion process and the rate of cell fusion. Both RGD and PHSRN domains were important in mediating FBGC formation at later implantation periods. These findings represent a mechanistic correlation between the role of protein functional architectures in ligand-receptor recognition and the post-ligation signaling events that control cellular behavior in vitro and in vivo.

Amino Acid Sequence↗

PubMed2002

Human macrophage adhesion on fibronectin: the role of substratum and intracellular signalling kinases.

Fibronectin and Arg-Gly-Asp (RGD)- and/or Pro-His-Ser-Arg-Asn (PHSRN)-containing oligopeptides were immobilized onto physicochemically distinct substrata: polyethyleneglycol-based networks or tissue culture polystyrene (TCPS). The role of selected signalling kinases in the adhesion of human primary blood-derived macrophages on these modified substrata was investigated. We demonstrated that the protein tyrosine kinase (PTK) or protein serine/threonine kinase (PSK) dependency and the PTK-PSK cross-talk compensation for macrophage adhesion varied dynamically with the substratum modification and the culture time. The inhibition of MAPK kinase (MAPKK) decreased macrophage adhesion on TCPS, whereas the inhibition of phosphoinositide-3 kinase (PI3 kinase) decreased macrophage adhesion on networks at 24 h. The PI3 kinase-protein kinase C (PKC)-MAPK cascade was involved in macrophage adhesion on fibronectin-preadsorbed TCPS or networks but not on fibronectin-grafted networks. This fibronectin-mediated adhesion signalling involved both RGD and PHSRN sequences in a form of G(3)RGDG(6)PHSRNG on TCPS but not on networks. Furthermore, G(3)RGDG(6)PHSRNG grafted onto networks evoked unique signalling in macrophage adhesion from that preadsorbed onto networks. Thus, macrophage adhesion and the role of selected signalling kinases were modulated by the substratum and the ligand conjugation method.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2002

In vivo biocompatibility of gelatin-based hydrogels and interpenetrating networks.

The in vivo host response to two gelatin-based hydrogel systems of varying crosslinking modalities and loaded with the anti-inflammatory agent dexamethasone sodium phosphate was investigated. Either gelatin was chemically crosslinked with glutaraldehyde, or polyethyleneglycol diacrylate was photopolymerized around gelatin to form interpenetrating networks. The subcutaneous cage implant system was utilized to determine differential leukocyte concentrations in the inflammatory exudate surrounding the materials as indices for biocompatibility and drug efficacy in vivo. Most of the crosslinked gelatin-based materials, either via glutaraldehyde fixation or interpenetrating network formation, elicited stronger inflammatory responses than either of the starting materials, gelatin and polyethyleneglycol diacrylate. In general, dexamethasone delayed and intensified the inflammatory response. The loss of material mass did not correlate directly with the degree of cellular inflammatory response, but increased with longer implantation time and decreased with more extensive fixation.

Animals↗