3D printing of silver-doped polycaprolactone-poly(propylene succinate) composite scaffolds for skin tissue engineering

Scaffold-based tissue engineering approaches have been commonly used for skin regeneration or wound healings caused by diseases or trauma. For an ideal complete healing process, scaffold structures need to meet the criteria of biocompatibility, biodegradability, and antimicrobial properties, as well as to provide geometrical necessities for the regeneration of damaged tissue. In this study, design, synthesis and characterization of a three dimensional (3D) printable copolymer based on polycaprolactone-block-poly(1,3-propylene succinate) (PCL-PPSu) including anti-microbial silver particles is presented. 3D printing of PCL-PPSu copolymers provided a lower processing temperature compared to neat PCL, hence, inclusion of temperature-sensitive bioactive reagents into the developed copolymer could be realized. In addition, 3D printed block copolymer showed an enhanced hydrolytic and enzymatic degradation behavior. Cell viability and cytotoxicity of the developed copolymer were evaluated by using human dermal fibroblast (HDF) cells. The addition of silver nitrate within the polymer matrix resulted in a significant decrease in the adhesion of different types of microorganisms on the scaffold without inducing any cytotoxicity on HDF cells in vitro. The results suggested that 3D printed PCL-PPSu scaffolds containing anti-microbial silver particles could be considered as a promising biomaterial for emerging skin regenerative therapies, in the light of its adaptability to 3D printing technology, low-processing temperature, enhanced degradation behavior and antimicrobial properties.

[1]  C. Majewski,et al.  Use of silver-based additives for the development of antibacterial functionality in Laser Sintered polyamide 12 parts , 2020, Scientific Reports.

[2]  B. Erman,et al.  Nanocomposite Bioinks Based on Agarose and 2D Nanosilicates with Tunable Flow Properties and Bioactivity for 3D Bioprinting. , 2019, ACS applied bio materials.

[3]  Jun Xu,et al.  Preparation and Characterization of Poly(butylene succinate)/Polylactide Blends for Fused Deposition Modeling 3D Printing , 2018, ACS omega.

[4]  Margaret J. Sobkowicz,et al.  Enzymatic degradation of poly (butylene succinate-co-hexamethylene succinate) , 2018, Polymer Degradation and Stability.

[5]  Renata Jachowicz,et al.  3D Printing in Pharmaceutical and Medical Applications – Recent Achievements and Challenges , 2018, Pharmaceutical Research.

[6]  Z. Qian,et al.  Injectable Hybrid Poly(ε-caprolactone)-b-poly(ethylene glycol)-b-poly(ε-caprolactone) Porous Microspheres/Alginate Hydrogel Cross-linked by Calcium Gluconate Crystals Deposited in the Pores of Microspheres Improved Skin Wound Healing. , 2018, ACS biomaterials science & engineering.

[7]  T. Su,et al.  Effect of Hydroxyl Monomers on the Enzymatic Degradation of Poly(ethylene succinate), Poly(butylene succinate), and Poly(hexylene succinate) , 2018, Polymers.

[8]  Mahdi Karimi,et al.  Nanomedicine and advanced technologies for burns: Preventing infection and facilitating wound healing , 2017, Advanced drug delivery reviews.

[9]  Ayesha Al-Sabah,et al.  Skin tissue engineering using 3D bioprinting: An evolving research field. , 2018, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[10]  G. Rella,et al.  Development of a bioactive glass-polymer composite for wound healing applications. , 2017, Materials science & engineering. C, Materials for biological applications.

[11]  J. Datta,et al.  Structure analysis and thermal degradation characteristics of bio-based poly(propylene succinate)s obtained by using different catalyst amounts , 2017, Journal of Thermal Analysis and Calorimetry.

[12]  T. Baran,et al.  Is 3D printing safe? Analysis of the thermal treatment of thermoplastics: ABS, PLA, PET, and nylon , 2017, Journal of occupational and environmental hygiene.

[13]  Margaret J. Sobkowicz,et al.  Bio-based poly(butylene succinate-co-hexamethylene succinate) copolyesters with tunable thermal and mechanical properties , 2017 .

[14]  S. Bahrami,et al.  Antibacterial performance and in vivo diabetic wound healing of curcumin loaded gum tragacanth/poly(ε-caprolactone) electrospun nanofibers. , 2016, Materials science & engineering. C, Materials for biological applications.

[15]  Y. Menceloglu,et al.  Multifunctional 3D printing of heterogeneous hydrogel structures , 2016, Scientific Reports.

[16]  L. Ceseracciu,et al.  Fumarate-loaded electrospun nanofibers with anti-inflammatory activity for fast recovery of mild skin burns , 2016, Biomedical materials.

[17]  Toby Brown,et al.  Poly(ε-caprolactone) Scaffolds Fabricated by Melt Electrospinning for Bone Tissue Engineering , 2016, Materials.

[18]  Antonios G. Mikos,et al.  Extrusion-Based 3D Printing of Poly(propylene fumarate) in a Full-Factorial Design. , 2016, ACS biomaterials science & engineering.

[19]  Rita Gamberini,et al.  Poly(butylene succinate)-based polyesters for biomedical applications: A review , 2016 .

[20]  M. Al-Omair.  Synthesis of Antibacterial Silver–Poly(ɛ-caprolactone)-Methacrylic Acid Graft Copolymer Nanofibers and Their Evaluation as Potential Wound Dressing , 2015 .

[21]  E. Björklund,et al.  Thermal stability assessment of antibiotics in moderate temperature and subcritical water using a pressurized dynamic flow-through system , 2015 .

[22]  Francesco Stellacci,et al.  Antibacterial activity of silver nanoparticles: A surface science insight , 2015 .

[23]  A. Boccaccini,et al.  Evaluation of silica-nanotubes and strontium hydroxyapatite nanorods as appropriate nanoadditives for poly(butylene succinate) biodegradable polyester for biomedical applications , 2014 .

[24]  Jingyan Dong,et al.  Hybrid hierarchical fabrication of three-dimensional scaffolds , 2014 .

[25]  G G Wallace,et al.  Coaxial additive manufacture of biomaterial composite scaffolds for tissue engineering , 2014, Biofabrication.

[26]  M. Prabhakaran,et al.  Advances in drug delivery via electrospun and electrosprayed nanomaterials , 2013, International journal of nanomedicine.

[27]  J. Malda,et al.  Biofabrication of multi-material anatomically shaped tissue constructs , 2013, Biofabrication.

[28]  Bernd Giese,et al.  Nanobio silver: its interactions with peptides and bacteria, and its uses in medicine. , 2013, Chemical reviews.

[29]  Paulo Jorge Da Silva bartolo,et al.  Characterisation of PCL and PCL/PLA Scaffolds for Tissue Engineering☆ , 2013 .

[30]  Shih-Hao Wang,et al.  Evaluation of silver-containing activated carbon fiber for wound healing study: In vitro and in vivo. , 2012, Journal of biomedical materials research. Part B, Applied biomaterials.

[31]  Geunhyung Kim,et al.  Electrospun PCL/phlorotannin nanofibres for tissue engineering: physical properties and cellular activities. , 2012, Carbohydrate polymers.

[32]  P. Bártolo,et al.  Additive manufacturing of tissues and organs , 2012 .

[33]  李春成,et al.  Synthesis of high-impact biodegradable multiblock copolymers comprising of poly(butylene succinate) and poly(1,2-propylene succinate) with hexamethylene diisocyanate as chain extender , 2011 .

[34]  A. Martínez-Richa,et al.  Hydrolytic degradation of poly(ε‐caprolactone) with different end groups and poly(ε‐caprolactone‐co‐γ‐butyrolactone): characterization and kinetics of hydrocortisone delivery , 2011 .

[35]  Dujing Wang,et al.  Synthesis of high‐impact biodegradable multiblock copolymers comprising of poly(butylene succinate) and poly(1,2‐propylene succinate) with hexamethylene diisocyanate as chain extender , 2011 .

[36]  E. Fortunati,et al.  Biodegradable polymer matrix nanocomposites for tissue engineering: A review , 2010 .

[37]  Dujing Wang,et al.  Multiblock copolymers composed of poly(butylene succinate) and poly(1,2-propylene succinate): Effect of molar ratio of diisocyanate to polyester-diols on crosslink densities, thermal properties, mechanical properties and biodegradability , 2010 .

[38]  Huarong Nie,et al.  Novel poly(butylene succinate-co-lactic acid) copolyesters: Synthesis, crystallization, and enzymatic degradation , 2010 .

[39]  C. Lim,et al.  Tissue scaffolds for skin wound healing and dermal reconstruction. , 2010, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[40]  J. de Brito,et al.  Hyperbranched polyglycerol electrospun nanofibers for wound dressing applications. , 2010, Acta biomaterialia.

[41]  P. K. Sehgal,et al.  Triphala incorporated collagen sponge--a smart biomaterial for infected dermal wound healing. , 2010, The Journal of surgical research.

[42]  D. Hutmacher,et al.  The return of a forgotten polymer : Polycaprolactone in the 21st century , 2009 .

[43]  Wei Sun,et al.  Precision extruding deposition (PED) fabrication of polycaprolactone (PCL) scaffolds for bone tissue engineering , 2009, Biofabrication.

[44]  M. Rai,et al.  Silver nanoparticles as a new generation of antimicrobials. , 2009, Biotechnology advances.

[45]  G. Lazarus,et al.  Treating the chronic wound: A practical approach to the care of nonhealing wounds and wound care dressings. , 2008, Journal of the American Academy of Dermatology.

[46]  K. Chrissafis,et al.  Synthesis, characterization, and thermal degradation mechanism of fast biodegradable PPSu/PCL copolymers , 2007 .

[47]  George Z. Papageorgiou,et al.  Miscibility and enzymatic degradation studies of poly(ε-caprolactone)/poly(propylene succinate) blends , 2007 .

[48]  Michael T. Wilson,et al.  Antimicrobial effect of silver-doped phosphate-based glasses. , 2006, Journal of biomedical materials research. Part A.

[49]  M. Vallet‐Regí,et al.  Long term degradation of poly(ɛ-caprolactone) films in biologically related fluids , 2006 .

[50]  D W Hutmacher,et al.  Fabrication using a rapid prototyping system and in vitro characterization of PEG-PCL-PLA scaffolds for tissue engineering , 2005, Journal of biomaterials science. Polymer edition.

[51]  Philippe Dumas,et al.  FTIR study of polycaprolactone chain organization at interfaces. , 2004, Journal of colloid and interface science.

[52]  S. Stevens,et al.  Multiple parameters for the comprehensive evaluation of the susceptibility of Escherichia coli to the silver ion , 2004, Biometals.

[53]  J. Nagy,et al.  Blends of polycaprolactone with polyvinylalcohol: a DSC, optical microscopy and solid state NMR study , 1999 .

[54]  W. Traub,et al.  Heat stability of the antimicrobial activity of sixty-two antibacterial agents. , 1995, The Journal of antimicrobial chemotherapy.