Biomedical subjects

You Han Bae

Publications and source records attributed to You Han Bae.

At least 37 records · Page 2Linked to original sources

PubMed2004

Caged pancreatic islet for IDDM.

The goals of this research are to improve the functionality (insulin secretion rate and pattern) and to expand the life-span of immunoprotected pancreatic islets. The low functionality (less than 15% of the insulin release rate of native islets in pancreas) required a large number of islets within the implant, which causes complications in surgery and discomfort for patients. The limited life-span of the islets in a biohybrid artificial pancreas (BAP) may require frequent cell reseeding and cause further supply problems in islet transplantation. Improved islet functionality and prolonged life-span will minimize the volume of the BAP by reducing the number of islets needed for diabetic patients to achieve normoglycaemia and reduce problems associated with islet supply. It is hypothesized in this research that 1) by mimicking facilitated oxygen transport in avascular tissues, the immunoprotected islets release a higher amount of insulin, recover their intrinsic biphasic release pattern, and prolong their life-span, and 2) insulinotropic agents further promote insulin secretion from islets. Based on these hypotheses, a new BAP system will be designed which contains the water-soluble polymeric conjugates of oxygen carriers (or oxygen binding vehicles) and islet stimulants of sulfonylurea compounds and glucagon-like insulinotropic peptide-1 with entrapped islets in the BAP. The research examines their effects on islet viability, the amount of insulin secretion, the insulin release profile, and the life-span of immunoprotected pancreatic islets. Especially, the combined synergy effects of both hypotheses will be emphasized. The successful results in improving functionality and life-span of islets entrapped in an immunoprotected membrane can be applied in the delivery of microencapsulated therapeutic cells and to the miniaturization of a BAP. In addition, the approaches proposed in this research will provide a potential solution to the shortage problem of human cell or tissue sources.

Diabetes Mellitus, Type 1↗

PubMed2004

Albumin loaded microsphere of amphiphilic poly(ethylene glycol)/ poly(alpha-ester) multiblock copolymer.

The purpose of this study is to investigate the microspheres (MS) based on (AB)(n) type amphiphilic multiblock copolymers for sustained and complete release of a model protein, bovine serum albumin (BSA). The MS were prepared by a modified water-in-oil-in-water (W/O/W) double emulsion method using amphiphilic multiblock copolymers consisting of poly(ethylene glycol) (PEG) and a poly(alpha-ester), poly(epsilon-caprolactone) (PCL) or poly(l-lactic acid) (PLLA). The size of MS and encapsulation efficiency of BSA within MS were not noticeably influenced by the copolymer composition used in this experiment. While BSA was completely released from PEG/PLLA MS through matrix erosion and the diffusion of BSA, it was released only to an extent of 60% from PEG/PCL MS solely through the diffusion process. However, the release of BSA from PEG/PCL MS dramatically increased and then reached 100% release in 10 days after thermal treatment of the MS at 50 degrees C for 30 min in the middle of release test (on day 15).

Delayed-Action Preparations↗

PubMed2004

Protection of insulin secreting cells from nitric oxide induced cellular damage by crosslinked hemoglobin.

Pancreatic islets and insulinoma cells are particularly vulnerable to serious damage by cytotoxic nitric oxide (NO) and/or oxidative stress, most probably due to their low expression levels of antioxidant enzymes. This cellular damage has been regarded as one of major obstacles to success of encapsulated islet transplantation for the treatment of type 1 diabetes. As an approach to preventing NO induced damage, crosslinked hemoglobin (Hb-C) with poly(ethylene glycol) was co-encapsulated with rat islets or insulinoma cells (RINm5F) in alginate/poly(L-lysine)/alginate microcapsules. Hb-C effectively protected the cells from NO damage, generated by treating the cell microcapsules with S-nitroso-N-acetylpenicillamine (SNAP, a nitric oxide donor) at concentrations up to 400 microM, preserving higher viability and insulin secretion than a control group (no SNAP and no Hb-C). When the cells were incubated with SNAP without Hb, there was SNAP concentration dependent cellular damage, and a colorimetric TUNEL assay revealed a typical cell apoptosis sign, indicating DNA damages.

Animals↗

PubMed2004

pH-dependent elution profiles of selected proteins in HPLC having a stationary phase modified with pH-sensitive sulfonamide polymers.

An approach to controlling protein interactions with silica (glass) beads grafted with pH-sensitive copolymers of a sulfonamide and N,N-dimethylacrylamide is proposed. The bead surface was modified with poly(N.N-dimethyl acrylamide-co-methacryloyl sulfadimethoxine), which exhibits hydrophobic/hydrophilic switching around pH 7.0. Phase transition in the aqueous solution, the wettability change of the modified surface and surface tension of the polymer-grafted glass surface was characterized by changes in turbidity and the dynamic contact angle as a function of pH. The discontinuous phase transition in the copolymer solution shifted to a higher pH region as the composition of sulfadimethoxine monomer (SDM) was increased. However, the transition pH in continuous wettability changes on the modified surface was not affected by polymer composition due to differences in the dynamic motion. The ionized SDM of the copolymers enhanced wettability. Therefore, the advancing contact angle of the surface decreased by 45 degrees above pH 7.0, whereas wettability at low pH values was low due to the hydrophobic surface. Elution behavior of the selected four model proteins with different pI (bovine serum albumin (pI 5.0), insulin (pI 5.3), fibrinogen (pI 6.1) and myoglobin (pI 7.1)) was investigated by using pH-sensitive copolymer-modified glass beads at four pH values (5.0, 6.0, 7.0 and 8.0). Retention time of the proteins in pH-sensitive aqueous chromatography was easily regulated by eluent pH that controls the proportion of electrostatic and hydrophobic interactions between the stationary phase and the protein. At pH 5.0, hydrophobic interaction on the deionized polymer-grafted surface is an important force in separating the proteins. However, identification of the proteins at pH 7.0 was effectively facilitated due to the electrostatic interaction between the negatively charged polymer support and positive charges on protein.

Biocompatible Materials↗

PubMed2003

Polymeric micelle for tumor pH and folate-mediated targeting.

Novel pH-sensitive polymeric mixed micelles composed of poly(L-histidine) (polyHis; M(w) 5000)/PEG (M(n) 2000) and poly(L-lactic acid) (PLLA) (M(n) 3000)/PEG (M(n) 2000) block copolymers with or without folate conjugation were prepared by diafiltration. The micelles were investigated for pH-dependent drug release, folate receptor-mediated internalization and cytotoxicity using MCF-7 cells in vitro. The polyHis/PEG micelles showed accelerated adriamycin release as the pH decreased from 8.0. When the cumulative release for 24 h was plotted as a function of pH, the gradual transition in release rate appeared in a pH range from 8.0 to 6.8. In order to tailor the triggering pH of the polymeric micelles to the more acidic extracellular pH of tumors, while improving the micelle stability at pH 7.4, the PLLA/PEG block copolymer was blended with polyHis/PEG to form mixed micelles. Blending shifted the triggering pH to a lower value. Depending on the amount of PLLA/PEG, the mixed micelles were destabilized in the pH range of 7.2-6.6 (triggering pH for adriamycin release). When the mixed micelles were conjugated with folic acid, the in vitro results demonstrated that the micelles were more effective in tumor cell kill due to accelerated drug release and folate receptor-mediated tumor uptake. In addition, after internalization polyHis was found to be effective for cytosolic ADR delivery by virtue of fusogenic activity. This approach is expected to be useful for treatment of solid tumors in vivo.

Antibiotics, Antineoplastic↗

PubMed2003

Poly(L-histidine)-PEG block copolymer micelles and pH-induced destabilization.

Poly(L-histidine)-poly(ethylene glycol) diblock copolymers (polyHis-b-PEG) were prepared and used for the construction of polymeric micelles responding to local pH changes in the body. PolyHis was synthesized by ring opening polymerization of L-histidine N-carboxyanhydride, the imidazole amine group of which was protected by the dinitrophenyl group. The resulting polymer (M(n): 5,000 g/mole) was coupled to poly(ethylene glycol) (M(n): 2,000 g/mole) via an amide linkage using the dicyclohexyl carbodiimide and N-hydroxysuccinimide-mediated reaction. The block copolymer in dimethyl sulfoxide formed polymeric micelles on diafiltration against a borate buffer at pH 8. Dynamic light scattering and atomic force microscopy showed the micelles were spherical, diameter approximately 114 nm, with a unimodal distribution. The critical micelle concentration (CMC) at pH 8.0 was 2.3 mg/l. The CMC increased markedly on decreasing the pH of the diafiltration medium below 7.2. Micelles prepared at pH 8.0 were gradually destabilized below pH 7.4, as evidenced by a slight increase in light transmittance, an alteration in size distribution, and a decrease in the pyrene fluorescence intensity. It was concluded that the ionization of the polyHis block forming the micelle core determined the pH-dependent CMC and stability. After further optimization of the pH-sensitivity, pH-sensitive micelles are expected to have application for solid tumor treatment, exploiting the fact that most solid tumors have an acidic extracellular pH.

Buffers↗

PubMed2003

Adriamycin loaded pullulan acetate/sulfonamide conjugate nanoparticles responding to tumor pH: pH-dependent cell interaction, internalization and cytotoxicity in vitro.

The cytotoxicity of adriamycin (ADR)-loaded and pH-sensitive nanoparticles made of pullulan acetate (PA) and sulfonamide (sulfadimethoxine; SDM) (PA/SDM) conjugate to a breast tumor cell line (MCF-7) was investigated to test the feasibility of the nanoparticles in targeting acidic tumor extracellular pH (pH(e)). At pH 6.8, ADR loaded PA/SDM nanoparticles showed cytotoxicity in the cell culture experiment, comparable to that of free ADR at the same ADR concentrations, while the relative cytotoxicity at pH 7.4 was low at the tested concentration range. This pronounced cytotoxicity of the nanoparticles at low pH was attributed to the accelerated release of ADR triggered by pH, enhanced interaction with cells, and internalization. At pH 6.8 and 6.4, the PA/SDM nanoparticles aggressively bounded to MCF-7 cells, probably due to interactions of the cells with hydrophobized nanoparticle surfaces caused by SDM deionization. A confocal laser microscopic study revealed intracellular localization of the drug-loaded nanoparticles. Based on these findings, the pH-sensitive nanoparticles deserve further investigation with an in vivo animal model as a targeted carrier of pH(e).

Acetates↗

PubMed2003

Hydrogels based on poly(ethylene oxide) and poly(tetramethylene oxide) or poly(dimethyl siloxane). III. In vivo biocompatibility and biostability.

To investigate the effects of polymer chemistry and topology (linear or graft copolymer) on in vivo biocompatibility and biostability based on cage implant system, various hydrogels, composed of short hydrophilic [polyethylene oxide (PEO)] and hydrophobic block, were prepared by polycondensation reaction. Poly(tetramethylene oxide) (PTMO) or poly(dimethyl siloxane) (PDMS) was chosen as a hydrophobic block because of their wide utilization as a biomaterial. By using the specimens retrieved from rats killed after 1, 2, 3, 5, and 7 weeks' implantation, cellular and material responses were assessed. Most hydrogels showed a comparable value of macrophage density to Pellethane(R), control polymer, whereas they did significantly lower foreign body giant cell (FBGC) density and coverage because of the presence of PEO. However, PEO block length and polymer topology did not affect macrophage adhesion and FBGC formation in our polymer composition. The hydrogel based on PDMS alone showed significantly lower macrophage density and FBGC density than Pellethane(R), indicating that PDMS plays a role in inhibiting cellular adhesion. The results obtained from gel permeation chromatography curve and Fourier transform infrared spectra exhibited that all the polymers were susceptible to oxidative degradation in vivo. Although Pellethane(R) revealed surface degradation by 5 weeks in vivo, hydrogels showed rapid degradation in the bulk within 2 weeks because of the penetration of oxidative chemicals released from phagocytic cells into PEO domain of phase-separated hydrogels. The more significant degradation was observed in the hydrogels with longer PEO block and PTMO as a hydrophobic block instead of PDMS. It was evident that the minor degradation could be achieved by grafting PEO and adopting PDMS as a hydrophobic block in the hydrogel.

Animals↗

PubMed2003

A sulfonamide based glucose-responsive hydrogel with covalently immobilized glucose oxidase and catalase.

A new glucose-sensitive hydrogel, based on sulfonamide chemistry with covalently conjugated glucose oxidase and catalase, was synthesized and tested. The pH-induced full swelling transition of the gel occurred in the range of pH 6.5 approximately 7.5. In a glucose concentration range of 0-300 mg/dl in an isotonic phosphate buffered saline solution (pH 7.4), the pH inside the gel varied from pH 7.4 to 7.2. At the same glucose concentration range, the gel showed reversible glucose dependent swelling without hysteresis from 12 to 8, expressed in water (g)/polymer (g).

Catalase↗

PubMed2003

Insulinotropic activity of sulfonylurea/pullulan conjugate in rat islet microcapsule.

The in vitro long-term effect of a water-soluble sulfonylurea/pullulan conjugate (SUP) on insulinotropic activity and cell viability was investigated using rat pancreatic islets co-entrapped with SUP in conventional alginate-poly(L-lysine) microcapsules. The conjugate was synthesized by coupling a carboxylated glibenclamide derivative to a polysaccharide, pullulan (MW=200,000). In vitro static experiment showed that sulfonylurea concentration in SUP over 50 microM was required to stimulate the rat islets. In a dynamic insulin secretion test, the microcapsules of islets with SUP regained the insulin secretion pattern comparable to that of free islets, while those without SUP showed impaired insulin secretion. The long-term (1 month) culture experiment demonstrated that the microcapsules of islets with SUP, with well-preserved morphology, presented higher insulin secretion level and better ability in responding to glucose changes than those without SUP.

Alginates↗

PubMed2003

A glucose oxidase electrode based on polypyrrole with polyanion/PEG/enzyme conjugate dopant.

This study investigated a new glucose sensor prepared by electrochemical polymerization of pyrrole with polyanion/poly(ethylene glycol) (PEG)/glucose oxidase (GOD) conjugate dopants. GOD was coupled to a strong polyanion, poly(2-acrylamido-2-methylpropane sulfonic acid) (AMPS) via PEG spacer to effectively and reproducibly immobilize GOD within a polypyrrole matrix onto a Pt electrode surface. PEGs with four different chain lengths (1000, 2000, 3000, and 4000) were used as spacers to study the spacer length effect on enzyme immobilization and electrode function. After conjugation, more than 90% of the GOD bioactivity was preserved and the bioactivity of the conjugated GOD increased with longer PEG spacers. The resulting polyanion/PEG/GOD conjugate was used as a dopant for electropolymerizing pyrrole. The activity of the immobilized enzyme on the electrode ranged from 119 to 209 mU cm(-2) and the bioactivity increased with the use of longer PEG spacers. The amperometric response of the enzyme electrode was linear up to 20 mM glucose concentration with a sensitivity ranging from 180 to 270 nA mM(-1) cm(-2). The kinetic parameters Michaelis-Menten constant (K(M)(app)) and maximum current density (j(max)) depended on the amount of active enzyme, level of substrate diffusion, and PEG spacer length. An increase in the electrical charge passed during polymerization (thus, increasing polypyrrole thickness) to 255 mC cm(-2) increased the sensitivity of the enzyme electrode because of the greater amount of incorporated enzyme. However, although the amount of incorporated GOD continued to increase when the charge increased above 255 mC cm(-2), the sensitivity began to decline gradually. The condition for preparing the enzyme electrode was optimized at 800 mV potential with a dopant concentration of 1 mg ml(-1).

Biosensing Techniques↗

PubMed2003

In situ accelerated degradation of polyoxyethylene/poly(epsilon-caprolactone) multiblock copolymer by moderate thermal treatment.

Alternating amphiphilic multiblock copolymers, consisting of polyoxyethylene (POE) and poly(epsilon-caprolactone) (PCL) of various lengths, were synthesized by a polycondensation reaction between dicarboxylated PEG and dihydroxyl PCL. The polymer formed a physical hydrogel by PCL crystallization. For in vitro hydrolysis in phosphate-buffered saline solution, the change of molecular weight depended on the composing block length of POE. The polymer with longer POE showed a faster decline in molecular weight. The mass remaining at the end of two weeks at 25 degrees C was more than 95 w%. However, when the swollen hydrogels were exposed to temperatures slightly above PCL melting point for 30 min, the degradation rate was accelerated and the mass remaining dropped to less than 10 wt% in one week. In vivo degradation after hydrogel implantation, the polymer degraded as under in vitro. However, the implant irradiated with infrared (IR) accelerated its degradation similar to a treatment with elevated temperature.

Calorimetry, Differential Scanning↗

PubMed2003

Norfloxacin-releasing urethral catheter for long-term catheterization.

Norfloxacin-releasing urethral catheters were prepared for the purpose of preventing urinary tract infections during long-term catheterization. The outer and inner surfaces of the catheters were coated with poly(ethylene-co-vinyl acetate) (EVA) and an amphiphilic multiblock co-polymer (PEO2kPDMS), composed of poly(ethylene oxide) and poly(dimethyl siloxane). Norfloxacin, a fluoroquinolone synthetic antibiotic, was impregnated into a coating layer. The in vitro drug release behavior was monitored for 30 days, the surface topography was investigated using scanning electron microscopy (SEM) and the antibacterial activity against different bacteria implicated in urinary tract infection was evaluated by the in vitro inhibition zone test. All the coated catheters showed continuous delivery of norfloxacin for up to 30 days owing to hydrophobic natures of norfloxacin and EVA. PEO2kPDMS incorporated in a coating layer produced a smooth and uniform surface. The coated catheters created considerable inhibition zones for 10 days against Escherichia coli. Klebsiella pneumoniae and Proteus vulgaris, indicating the continuous release of norfloxacin. Overall, it was evident that the catheters coated with EVA/PEO2kPDMS blends containing norfloxacin have a promising potential for the clinical use in patients undergoing long-term catheterization.

Anti-Bacterial Agents↗

PubMed2003

Gentamicin-releasing urethral catheter for short-term catheterization.

Urethral catheters, widely used for the drainage of the bladder, are associated with most urinary tract infections (UTIs) that account for 40% of all episodes occurring in acute-care hospitals. This study aimed to develop a gentamicin-releasing catheter that effectively prevents UTIs for short-term catheterization. For physical loading of gentamicin, the urethral catheters were coated by the simple dipping method with poly(ethylene-co-vinyl acetate) (EVA) and EVA/poly(ethylene oxide) (PEO) blends containing gentamicin. By varying the molecular weight (MW) and contents of PEO in the blends, various catheter surfaces were produced. In vitro drug release studies demonstrated that all the coated catheters exhibited sustained release up to 7 days; however, the release pattern was significantly dependant on the coating layers. Of the coated catheters, EVA/PEO (MW = 100k)-coated catheters were utilized to evaluate the antibacterial activity using an inhibition zone test, since they showed a promising drug release behavior and had PEO-rich biocompatible surfaces. In accordance with drug release behavior, EVA/PEO-coated catheters exhibited antibacterial activities for 7 days against Proteus vulgaris, Staphylococcus aureus and Staphylococcus epidermidis. These results imply that the catheters coated with EVA/PEO have a potential for short-term catheterization.

Anti-Bacterial Agents↗

PubMed2002

Biodegradable poly(ethylenimine) for plasmid DNA delivery.

Poly(ethylenimine) (PEI) has been known as an efficient gene carrier with the highest cationic charge potential. High transfection efficiency of PEI, along with its cytotoxicity, strongly depends on the molecular weight. Synthesis of cationic copolymers derived from the low molecular weight of PEI and hydrophilic poly(ethylene glycol) (PEG), which are water soluble and degradable under physiological conditions, was investigated for plasmid delivery. Hydrophilic PEG is expected to reduce the toxicity of the copolymer, improve the poor solubility of the PEI and DNA complexes, and help to introduce degradable bonds by reaction with the primary amines in the PEI. Considering the dependence of transfection efficiency and cytotoxicity on the molecular weight of the PEI, high transfection efficiency is expected from an increased molecular weight of the copolymer and low cytotoxicity from the introduction of PEG and the degradation of the copolymer into low molecular weight PEIs. Reaction conditions were carefully controlled to produce water soluble copolymers. Results from a gel retardation assay and zetapotentiometer indicated that complete neutralization of the complexes was achieved at the charge ratios of copolymer/pSV-beta-gal plasmid from 0.8 to 1.0 with the mean particle size of the polyplexes ranging from 129.8+/-0.9 to 151.8+/-3.4 nm. In vitro transfection efficiency of the synthesized copolymer increased up to three times higher than that of starting low molecular weight PEI, while the cell viability was maintained over 80%.

Cell Line↗

PubMed2002

pH-induced solubility transition of sulfonamide-based polymers.

As an approach to designing new pH-sensitive polymers for bio-related application, we have modified selected sulfonamides, with various pK(a), to polymerizable monomers. The pK(a) of the monomers, homopolymers, and copolymers with N,N-dimethylacrylamide were examined, and pH-induced phase transition behavior, particularly in solubility, was investigated. The pK(a) of sulfonamide monomers and polymers at 25 degrees C was slightly higher than those of corresponding sulfonamides but the enthalpy of the ionization was influenced due to interfering resonance structures that are present in the mother compounds. The solubility transition of each homopolymer in aqueous solutions occurred at a degree of ionization of 85-90%. For the copolymers, the solubility transition observed by light transmittance completed in a narrow pH range (0.2-0.3 pH units) and this transition pH shifted to a higher pH region with the increasing sulfonamide unit in the copolymer, though the pK(a) was not considerably changed. This polymer precipitation occurs because of the relative balance of overall hydrophilicity/hydrophobicity along the polymer chain. Because the unionized form of sulfonamide units is considered to be hydrophobic, the copolymer with higher content of sulfonamide unit requires a higher degree of ionization for solubilization and thus solubility transition occurred at higher pH.

Anti-Infective Agents↗

PubMed2002

Thermosensitive sol-gel reversible hydrogels.

Aqueous polymer solutions that are transformed into gels by changes in environmental conditions, such as temperature and pH, thus resulting in in situ hydrogel formation, have recently attracted the attention of many investigators for scientific interest and for practical biomedical or pharmaceutical applications. When the hydrogel is formed under physiological conditions and maintains its integrity for a desired period of time, the process may provide various advantages over conventional hydrogels. Because of the simplicity of pharmaceutical formulation by solution mixing, biocompatibility with biological systems, and convenient administration, the pharmaceutical and biomedical uses of the water-based sol-gel transition include solubilization of low-molecular-weight hydrophobic drugs, controlled release, labile biomacromolecule delivery, such as proteins and genes, cell immobilization, and tissue engineering. When the formed gel is proven to be biocompatible and biodegradable, producing non-toxic degradation products, it will provide further benefits for in vivo applications where degradation is desired. It is timely to summarize the polymeric systems that undergo sol-gel transitions, particularly due to temperature, with emphasis on the underlying transition mechanisms and potential delivery aspects. This review stresses the polymeric systems of natural or modified natural polymers, N-isopropylacrylamide copolymers, poly(ethylene oxide)/poly(propylene oxide) block copolymers, and poly(ethylene glycol)/poly(D,L-lactide-co-glycolide) block copolymers.

Drug Delivery Systems↗

PubMed2002

Hydrogels based on poly(ethylene oxide) and poly(tetramethylene oxide) or poly(dimethyl siloxane): synthesis, characterization, in vitro protein adsorption and platelet adhesion.

In vitro protein adsorption, platelet adhesion and activation on new hydrogel surfaces, composed of poly(ethylene oxide) (PEO) and poly(tetramethylene oxide) (PTMO) or poly(dimethyl siloxane) (PDMS), were investigated. By varying PEO length (MW = 2000 or 3400), hydrophobic components (PTMO or PDMS) or polymer topology (block or graft copolymers), various physical hydrogels were produced. Their structures were verified by 1H NMR and ATR-IR and the molecular weights were determined by gel permeation chromatography. The hydrogels were soluble in a variety of organic solvents, while absorbed a significant amount of water with preserved three-dimensional structure by physical crosslinking. The dynamic contact angle measurement revealed that the surface hydrophilicity increased by incorporating longer PEO, PEO grafting, and adopting PDMS as a hydrophobic segment instead of PTMO. It was observed from in vitro protein adsorption study that the hydrogels exhibited significantly lower adsorption of human serum albumin (HSA), human fibrinogen (HFg), and IgG, when compared with Pellethane, a commercial polyurethane taken as a control. The hydrogels were attractive for HSA but not sensitive to HFg and IgG. And more than 65% of the proteins detected on the surfaces of the hydrogels were reversibly detached by being treated with an SDS solution. It was evident that the hydrogels synthesized in this study were much more resistant to platelet adhesion than the control, which might depend on the composition of proteins adsorbed on the surfaces and their degree of denaturation. Among the hydrogels tested, PEO3,4kPDMS exhibited albumin-rich and platelet-resistant surfaces, implying a potential candidate for biomaterial.

Adsorption↗