title: Cell-Free HA-MA/PLGA Scaffolds with Radially Oriented Pores for In Situ Inductive Regeneration of Full Thickness Cartilage Defects.
abstract: A bioactive scaffold with desired microstructure is of great importance to induce infiltration of somatic and stem cells, and thereby to achieve the in situ inductive tissue regeneration. In this study, a scaffold with oriented pores in the radial direction is prepared by using methacrylated hyaluronic acid (HA-MA) via controlled directional cooling of a HA-MA solution, and followed with photo-crosslinking to stabilize the structure. Poly(lactide-co-glycolide) (PLGA) is further infiltrated to enhance the mechanical strength, resulting in a compressive modulus of 120 kPa. In vitro culture of bone marrow stem cells (BMSCs) reveals spontaneous cell aggregation inside this type of scaffold with a spherical morphology. In vivo transplantation of the cell-free scaffold in rabbit knees for 12 w regenerates simultaneously both cartilage and subchondral bone with a Wakitani score of 2.8. Moreover, the expression of inflammatory factor interleukin-1β (IL-1β) is down regulated, although tumor necrosis factor-α (TNF-α) is remarkably up regulated. With the anti-inflammatory, bioactive properties and good restoration of full thickness cartilage defect in vivo, the oriented macroporous HA-MA/PLGA hybrid scaffold has a great potential for the practical application in the in situ cartilage regeneration.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Yuankun
authors.initials: Y
authors.lastname: Dai
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Gao
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Lie
authors.initials: L
authors.lastname: Ma
authors.affiliation: Division of Bioengineering, School of Chemical & Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, N1.3-B2-13, 637457, Singapore.
authors.forename: Dongan
authors.initials: D
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
authors.forename: Changyou
authors.initials: C
authors.lastname: Gao
mesh_terms: D000818:Animals; D002356:Cartilage / Q000293:injuries / Q000502:physiology*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D007718:Knee Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D008689:Methacrylates / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D012038:Regeneration / Q000187:drug effects*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D008689:Methacrylates; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid
keywords: cartilage regeneration; hyaluronic acid; in situ inductivity; microstructure; scaffolds