Improved phenotype of rat islets in a macrocapsule by co-encapsulation with cross-linked Hb.
A number of rat islets were co-encapsulated in a diffusion chamber-type device, i.e., macrocapsule, with a thermoreversible polymeric extracellular matrix (ECM) and bioactive ingredient of cross-linked hemoglobin (Hb-C). The ECM was formed from an aqueous solution of N-isopropyl-acrylamide co-polymers with a small amount of acrylic acid, which exhibited unique sol-gel transition in a temperature range of 30-34 degrees C, without noticeable hysteresis. The incorporation of Hb-C in the islet macrocapsule showed a concentration-dependent effect on insulin secretion and viability of the entrapped islets. Insulin secretion stimulation by glucose and cell viability were more than doubled when compared with a control group (without Hb-C), at an optimum Hb-C concentration of 0.25 mM due to its unique oxygen transporting capacity. Furthermore, 0.25 mM Hb-C in the macrocapsule was able to support islet density up to 1000 islets/device in a 154 microl total volume without negative effects on islet functionality and viability. Hb-C incorporation is an effective strategy for a macrocapsule-type biohybrid artificial pancreas for Type-I diabetes treatment, which can be further developed to a rechargeable system by employing the thermoreversible ECM and designing a proper macrocapsule.
Kim
Yong Yeon
YY
Center for Biomaterials and Biotechnology, Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, 1 Oryong-dong, Puk-gu, Gwangju 500-712, South Korea.
Chae
Su Young
SY
Kim
Sungwon
S
Byun
Youngro
Y
Bae
You Han
YH
D000818:Animals; D002214:Capsules; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000737:chemistry; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D020100:Hydrogels; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D010108:Oxyhemoglobins / Q000494:pharmacology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002214:Capsules; D003432:Cross-Linking Reagents; D020100:Hydrogels; D007328:Insulin; D010108:Oxyhemoglobins; D005947:Glucose