A novel therapeutic design of microporous-structured biopolymer scaffolds for drug loading and delivery.
Three-dimensional (3-D) open-channeled scaffolds of biopolymers are a promising candidate matrix for tissue engineering. When scaffolds have the capacity to deliver bioactive molecules the potential for tissue regeneration should be greatly enhanced. In order to improve drug-delivery capacity, we exploit 3-D poly(lactic acid) (PLA) scaffolds by creating microporosity within the scaffold network. Macroporous channeled PLA with a controlled pore configuration was obtained by a robotic dispensing technique. In particular, a room temperature ionic liquid (RTIL) bearing hydrophilic counter-anions, such as OTf and Cl, was introduced to the biopolymer solution at varying ratios. The RTIL-biopolymer slurry was homogenized by ultrasonication, and then solidified through the robotic dispensing process, during which the biopolymer and RTIL formed a bicontinuous interpenetrating network. After ethanol wash-out treatment the RTIL was completely removed to leave highly microporous open channels throughout the PLA network. The resultant pore size was observed to be a few micrometers (average 2.43 μm) and microporosity was determined to be ∼ 70%. The microporous surface was also shown to favor initial cell adhesion, stimulating cell anchorage on the microporous structure. Furthermore, in vivo tissue responses assessed in rat subcutaneous tissue revealed good tissue compatibility, with minimal inflammatory reactions, while gathering a larger population of fibroblastic cells than the non-microporous scaffolds, and even facilitating invasion of the cells within the microporous structure. The efficacy of the micropore networks generated within the 3-D scaffolds in loading and releasing therapeutic molecules was addressed using antibiotic sodium ampicillin and protein cytochrome C as model drugs. The microporous scaffolds exhibited significantly enhanced drug loading capacity: 4-5 times increase in ampicillin and 9-10 times increase in cytochrome C compared to the non-microporous scaffolds. The release of ampicillin loaded within the microporous scaffolds was initially fast (∼ 85% for 1 week), and was then slowed down, showing a continual release up to a month. On the other hand, cytochrome C was shown to release in a highly sustainable manner over a month, without showing an initial burst release effect. This study provides a novel insight into the generation of 3-D biopolymer scaffolds with high performance in loading and delivery of biomolecules, facilitated by the creation of microporous channels through the scaffold network. The capacity to support tissue cells while in situ delivering drug molecules makes the current scaffolds potentially useful for therapeutic tissue engineering.
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
Biligzaya
B
Dorj
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
Jong-Eun
JE
Won
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
Odnoo
O
Purevdorj
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
Kapil D
KD
Patel
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
Joong-Hyun
JH
Kim
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea.
Eun-Jung
EJ
Lee
Institute of Tissue Regeneration Engineering (ITREN), Dankook University, South Korea; Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, South Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, South Korea. Electronic address: kimhw@dku.edu.
Hae-Won
HW
Kim
D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D001704:Biopolymers / Q000737:chemistry*; D045304:Cytochromes c / Q000378:metabolism; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D052578:Ionic Liquids / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008422:Materials Testing / Q000379:methods*; D051379:Mice; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D017207:Rats, Sprague-Dawley; D012371:Robotics; D013696:Temperature; D054457:Tissue Scaffolds / Q000737:chemistry*
D001704:Biopolymers; D052578:Ionic Liquids; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D000667:Ampicillin; D045304:Cytochromes c
3-D porous scaffolds; Drug loading capacity; Microporous structure; Phase separation; Sustained drug delivery