Layer-by-layer coated porous 3D printed hydroxyapatite composite scaffolds for controlled drug delivery.

Interconnected porous scaffolds are widely used in the applications of tissue repair and regeneration. Sustained local delivery of drugs and growth factors around the implanted scaffolds could accelerate the growth of cells and contribute to the regeneration of damaged tissues. In this study, porous hydroxyapatite composite scaffolds were prepared through 3D bio-printing for bone tissue engineering and were subsequently coated with chitosan and sodium hyaluronate by layer-by-layer (LBL) deposition. It was found that the LBL coating on the porous scaffolds could reduce the swelling ratio of scaffolds in size and increase the compressive strength by about 70%. The degradation rate of the scaffolds slowed down due to the LBL coating. Rhodamine B (RHB) and bovine serum albumin (BSA) were chosen as model drugs in order to understand the loading and release behaviors of the scaffolds. Small RHB molecules could penetrate deep into the LBL coated scaffolds and released a little slower than that without coating. Meanwhile, large BSA molecules showed faster release rate compared to that without coating. In addition, there was no significant cytotoxicity effect of these composite scaffolds towards MC-3T3E1 cells and the scaffolds provided proper conditions for cell adhesion and proliferation, indicating that the printed hydroxyapatite composite scaffolds exhibit a great potential in hard tissue engineering as a sustained delivery system.

[1]  Shengmin Zhang,et al.  Biomimetic self-assembly of apatite hybrid materials: from a single molecular template to bi-/multi-molecular templates. , 2014, Biotechnology advances.

[2]  Molly Stevens,et al.  From clinical imaging to implantation of 3D printed tissues , 2016, Nature Biotechnology.

[3]  Xingdong Zhang,et al.  Creating hierarchical porosity hydroxyapatite scaffolds with osteoinduction by three-dimensional printing and microwave sintering , 2017, Biofabrication.

[4]  Paula T Hammond,et al.  Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants. , 2011, Biomaterials.

[5]  S. Hollister Porous scaffold design for tissue engineering , 2005, Nature materials.

[6]  Jing Liang,et al.  Self-defensive antibacterial layer-by-layer hydrogel coatings with pH-triggered hydrophobicity. , 2015, Biomaterials.

[7]  R. Soares,et al.  Designing Biomaterials for 3D Printing. , 2016, ACS biomaterials science & engineering.

[8]  M. Vallet‐Regí,et al.  Fabrication of novel Si-doped hydroxyapatite/gelatine scaffolds by rapid prototyping for drug delivery and bone regeneration. , 2015, Acta biomaterialia.

[9]  Jason A Inzana,et al.  3D printing of composite calcium phosphate and collagen scaffolds for bone regeneration. , 2014, Biomaterials.

[10]  Dong-Woo Cho,et al.  A new method of fabricating a blend scaffold using an indirect three-dimensional printing technique , 2015, Biofabrication.

[11]  Jianzhong Fu,et al.  Bone regeneration in 3D printing bioactive ceramic scaffolds with improved tissue/material interface pore architecture in thin-wall bone defect , 2017, Biofabrication.

[12]  Y. Lvov,et al.  Sonication-Assisted Layer-by-Layer Assembly for Low Solubility Drug Nanoformulation. , 2015, ACS applied materials & interfaces.

[13]  Benjamin M Wu,et al.  Macro- and micro-designed chitosan-alginate scaffold architecture by three-dimensional printing and directional freezing , 2016, Biofabrication.

[14]  Zhongyi Jiang,et al.  Facile construction of multicompartment multienzyme system through layer-by-layer self-assembly and biomimetic mineralization. , 2011, ACS applied materials & interfaces.

[15]  Changqing Zhang,et al.  Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration. , 2014, Acta biomaterialia.

[16]  Peter X Ma,et al.  Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. , 2009, Biomaterials.

[17]  F. Sailhan,et al.  The performance of BMP-2 loaded TCP/HAP porous ceramics with a polyelectrolyte multilayer film coating. , 2011, Biomaterials.

[18]  Changchun Zhou,et al.  Biomimetic fabrication of a three-level hierarchical calcium phosphate/collagen/hydroxyapatite scaffold for bone tissue engineering , 2014, Biofabrication.

[19]  Ibrahim T. Ozbolat,et al.  The bioink: A comprehensive review on bioprintable materials. , 2017, Biotechnology advances.

[20]  S. Collins Bioprinting is changing regenerative medicine forever. , 2014, Stem cells and development.

[21]  S. Van Vlierberghe,et al.  Bioink properties before, during and after 3D bioprinting , 2016, Biofabrication.

[22]  Yilin Cao,et al.  Fabrication and surface modification of macroporous poly(L-lactic acid) and poly(L-lactic-co-glycolic acid) (70/30) cell scaffolds for human skin fibroblast cell culture. , 2002, Journal of biomedical materials research.

[23]  K H Kang,et al.  Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds , 2012, Biofabrication.

[24]  Deok‐Ho Kim,et al.  Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink , 2014, Nature Communications.

[25]  A. Bandyopadhyay,et al.  Bone tissue engineering using 3D printing , 2013 .

[26]  Dong-Woo Cho,et al.  Ornamenting 3D printed scaffolds with cell-laid extracellular matrix for bone tissue regeneration. , 2015, Biomaterials.

[27]  E. Chibowski,et al.  Synthesis of hydroxyapatite for biomedical applications. , 2017, Advances in colloid and interface science.

[28]  Ira Bhatnagar,et al.  Alginate composites for bone tissue engineering: a review. , 2015, International journal of biological macromolecules.

[29]  Bin Duan,et al.  Three-dimensional nanocomposite scaffolds fabricated via selective laser sintering for bone tissue engineering. , 2010, Acta biomaterialia.

[30]  Qilong Zhao,et al.  Cryogenic 3D printing for producing hierarchical porous and rhBMP-2-loaded Ca-P/PLLA nanocomposite scaffolds for bone tissue engineering , 2017, Biofabrication.

[31]  A. Boccaccini,et al.  Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. , 2006, Biomaterials.

[32]  Huifang Zhou,et al.  Recent advances in bioprinting techniques: approaches, applications and future prospects , 2016, Journal of Translational Medicine.

[33]  Gang Li,et al.  Three-dimensional CaP/gelatin lattice scaffolds with integrated osteoinductive surface topographies for bone tissue engineering , 2015, Biofabrication.

[34]  V. Chatap,et al.  Stimuli-sensitive layer-by-layer (LbL) self-assembly systems: targeting and biosensory applications. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[35]  A. del Campo,et al.  3D bioprinting of structural proteins. , 2017, Biomaterials.

[36]  Yong Wang,et al.  Nano hydroxyapatite particles promote osteogenesis in a three-dimensional bio-printing construct consisting of alginate/gelatin/hASCs , 2016 .

[37]  M. Collins,et al.  Hyaluronic acid based scaffolds for tissue engineering--a review. , 2013, Carbohydrate polymers.

[38]  Y. Shanjani,et al.  A novel bioprinting method and system for forming hybrid tissue engineering constructs , 2015, Biofabrication.