Bioactive polymers for biohybrid artificial pancreas.
To address the solution for some of the obstacles, such as low insulin secretion, limited lifespan and aggregation of transplanted islets, encountered in developing a biohybrid artificial pancreas (BAP), polymeric materials including a reversible polymeric extracellular matrix (ECM), crystallized glucagon-like peptide-1, and oxygen carrying polymers, were prepared and their potential utilities in designing a compact and rechargeable BAP were investigated. For a synthetic, reversible ECM, high molecular weight N-isopropylacrylamide copolymer with a small amount of acrylic acid (2 mole%) was synthesized by conventional radical polymerization in benzene, and its aqueous solution above a critical polymer concentration displayed a sol-gel transition temperature near physiological temperature (33-35 degrees C) without noticeable hysteresis. The physicochemical properties of the gel with islet compatibility proved that the synthetic ECM is an appropriate matrix which can make a BAP rechargeable. Glucagon-like peptide-1 (GLP-1, 7-37) is known to have a strong stimulatory effect on insulin secretion, particularly at high glucose concentrations. When zinc-crystallized GLP-1 was entrapped along with islets in a hollow fiber macrocapsule device, insulin secretion was enhanced at a high glucose concentration (300 mg/dl) with a >85% increase in insulin secretion after an induction period. The cross-linked hemoglobin with difunctional PEO (Hb-C) was prepared to increase the high molecular weight of Hb. This prevents diffusional loss when enclosed in an immunoprotecting membrane. The Hb-C, entrapped in microcapsules, enhanced insulin secretion and improved the viability of microencapsulated islets by promoting oxygen supply to islets. The introduction of the synthetic ECM, crystallized GLP-1, and Hb-C into a BAP may provide a basis for designing a compact and rechargeable BAP (macrocapsule).
Chae
S Y
SY
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City 84112, USA.
Kim
S W
SW
Bae
Y H
YH
D000818:Animals; D021522:Bioartificial Organs; D018929:Cell Culture Techniques / Q000379:methods; D003460:Crystallization; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D005934:Glucagon / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D006454:Hemoglobins / Q000737:chemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D011498:Protein Precursors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*
D006454:Hemoglobins; D007328:Insulin; D010446:Peptide Fragments; D011108:Polymers; D011498:Protein Precursors; D011092:Polyethylene Glycols; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D010100:Oxygen