Highlights
- •Polycaprolactone (PCL) is amongst the most widely used base polymer materials aimed at bone regeneration using both, electrospinning and 3D printing.
- •PCL is often followed by PLLA (poly-l-lactide) and PLGA (poly Lactic-co-Glycolic Acid) as base/ combination materials for fabricating electrospun scaffolds for bone regeneration.
- •For 3D printing technique, ceramic materials like hydroxyapatite (HA) and /βTCP (β-tricalcium phosphate) are more commonly used.
- •Chitosan is often used along with other materials to provide mechanical strength to scaffolds.
- •In vivo data is only available from a handful of the studies that investigate the above mentioned materilas in vitro.
Abstract
Critical-size long bone defects represent one of the major causes of fracture non-union
and remain a significant challenge in orthopaedic surgery. Two-stage procedures such
as a Masquelet technique demonstrate high level of success however their main disadvantage
is the need for a second surgery, which is required to remove the non-resorbable cement
spacer and to place the bone graft into the biological chamber formed by the ‘induced
membrane’. Recent research efforts have therefore been dedicated towards the design,
fabrication and testing of resorbable implants that could mimic the biological functions
of the cement spacer and the induced membrane. Amongst the various manufacturing techniques
used to fabricate these implants, three-dimensional (3D) printing and electrospinning
methods have gained a significant momentum due their high-level controllability, scalable
processing and relatively low cost. This review aims to present recent advances in
the evaluation of electrospun and 3D printed polymeric materials for critical-size,
long bone defect reconstruction, emphasizing both their beneficial properties and
current limitations. Furthermore, we present and discuss current state-of-the art
techniques required for characterisation of the materials’ physical, mechanical and
biological characteristics. These represent the essential first steps towards the
development of personalised implants for single-surgery, large defect reconstruction
in weight-bearing bones.
Keywords
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References
- Reconstruction of Long Bone Infections Using the Induced Membrane Technique: tips and Tricks.J Orthop Trauma. 2016; 30 (Jun): e188-e193
- The Masquelet technique: current concepts, animal models, and perspectives.J Tissue Eng Regen Med. 2020; 14: 10
- Very long-term results of post-traumatic bone defect reconstruction by the induced membrane technique.Orthopaedics & traumatology, surgery & research: OTSR, 2019: 105
- Challenges on optimization of 3D-printed bone scaffolds.Biomed Eng Online. 2020; 19: 1-33
- Induced periosteum a complex cellular scaffold for the treatment of large bone defects.Bone. 2013; 57: 8
- Induced Periosteum-Mimicking Membrane with Cell Barrier and Multipotential Stromal Cell (MSC) Homing Functionalities.Int J Mol Sci. 2020; 21: 16
- A crosslinked collagen membrane versus a noncrosslinked bilayer collagen membrane for supporting osteogenic functions of human bone marrowmultipotent stromal cells.European cells and materials. 2019; 37: 292-309
- Use of electrospinning technique for biomedical applications.Polymer (Guildf). 2008; 49: 5603-5621
- Development of biomimetic electrospun polymeric biomaterials for bone tissue engineering. A review.Journal of biomaterials science, polymer edition. 2019; 30: 1308-1355
- Polycaprolactone as biomaterial for bone scaffolds: review of literature.J Oral Biol Craniofac Res. 2020; 10: 381-388
- Strontium incorporated mineralized PLLA nanofibrous membranes for promoting bone defect repair.Colloids and Surfaces B: Biointerfaces. 2019; 179: 363-373
- 3D printed poly(ε-caprolactone) scaffolds function with simvastatin-loaded poly(lactic-co-glycolic acid) microspheres to repair load-bearing segmental bone defects.Experimental and therapeutic medicine, 2019: 17
- Design, Materials, and Mechanobiology of Biodegradable Scaffolds for Bone Tissue Engineering.Biomed Res Int. 2015; 2015: 21
- Recent Applications of Coaxial and Emulsion Electrospinning Methods in the Field of.Tissue Engineering. BioResearch. 2016; 5: 212-227
- A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects.J Biomater Appl. 2016; 31: 241-249
- Core-sheath micro/nano fiber membrane with antibacterial and osteogenic dual functions as biomimetic artificial periosteum for bone regeneration applications.Nanomedicine: Nanotechnology, Biology, and Medicine. 2019; 17: 124-136
- Embedding magnesium metallic particles in polycaprolactone nanofiber mesh improves applicability for biomedical applications.Acta Biomater. 2019; 98: 215-234
- Bilayer pifithrin-α loaded extracellular matrix/PLGA scaffolds for enhanced vascularized bone formation.Colloids and Surfaces B: Biointerfaces. 2020; : 190
- Dual-Peptide-Functionalized Nanofibrous Scaffolds Recruit Host Endothelial Progenitor Cells for Vasculogenesis to Repair Calvarial Defects.ACS Appl Mater Interfaces. 2020; 12: 3474-3493
- Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects.PLoS ONE. 2011; 6: e25462
- Superelastic, Superabsorbent and 3D Nanofiber-Assembled Scaffold for Tissue Engineering.Colloids and Surfaces B: Biointerfaces. 2016; 142: 165-172
- Mechanical property and biological performance of electrospun silk fibroin-polycaprolactone scaffolds with aligned fibers.Journal of biomaterials science Polymer edition. 2016; 27: 263-275
- Fabrication of poly(glycerol sebacate) fibrous membranes by coaxial electrospinning: influence of shell and core solutions.J Mech Behav Biomed Mater. 2016; 63: 220-231
- Alkali-Mediated Miscibility of Gelatin/Polycaprolactone for Electrospinning Homogeneous Composite Nanofibers for Tissue Scaffolding.Macromolecular Bioscence. 2017; 17: 1-10
- Electrospinning of Polycaprolactone/Pluronic F127 dissolved in glacial acetic acid: fibrous scaffolds fabrication, characterization and in vitro evaluation.Journal of biomaterials science Polymer edition. 2018; 29: 1568-5624
- ECM Decorated Electrospun Nanofiber for Improving Bone Tissue Regeneration.Polymers (Basel). 2018; 10: 272
- Electrospun PCL nanofibers blended with Wattakaka volubilis active phytochemicals for bone and cartilage tissue engineering.Nanomedicine: nanotechnology, biology, and medicine. 2019; 21: 10
- Composite scaffold obtained by electro-hydrodynamic technique for infection prevention and treatment in bone repair.Int J Pharm. 2019; 557: 162-169
- Electrospin-Coating of Paper: a Natural Extracellular Matrix Inspired Design of Scaffold.Polymers (Basel). 2019; 11: 650
- Promoting osteogenic differentiation of BMSCs via mineralization of polylactide/gelatin composite fibers in cell culture medium.Materials Science & Engineering C. 2019; 100: 862-873
- Preparation of electrospun nanofibers with desired microstructures using a programmed three-dimensional (3D) nanofiber collector.Materials science & engineering C, Materials for biological applications. 2020; 106: 10
- Mechanical properties of nasal fascia and periosteum.Clinical biomechanics. Clinical Biomechanics. 2003; 18: 760-764
- Chitosan as a biomaterial — structure, properties, and electrospun nanofibers.Concepts, Compounds and the Alternatives of Antibacterials: IntechOpen, 2015
- Chitosan Derivatives and Their Application in Biomedicine.Int J Mol Sci. 2020; 21: 487
- Natural Polymeric Scaffolds in Bone Regeneration.Front Bioeng Biotechnol. 2020; 8: 28
- Biomimetic mineralization of carboxymethyl chitosan nanofibers with improved osteogenic activity in vitro and in vivo.Carbohydr Polym. 2018; 195: 225-234
- In vivo analysis of vascularization and biocompatibility of electrospun polycaprolactone fibre mats in the rat femur chamber.J Tissue Eng Regen Med. 2019; 13: 1190-1202
- Novel naturally crosslinked electrospun nanofibrous chitosan mats for guided bone regeneration membranes: material characterization and cytocompatibility.J Tissue Eng Regen Med. 2015; 9: 577-583
- Osteoblast biocompatibility of novel chitosan crosslinker, hexamethylene-1,6-diaminocarboxysulfonate.Journal of biomedical materials research Part A. 2015; 103: 3026-3033
- Potential of electrospun chitosan fibers as a surface layer in functionally graded GTR membrane for periodontal regeneration.Dental materials: official publication of the Academy of Dental Materials. 2017; 33: 71-83
- Optimization of electrospinning process & parameters for producing defect-free chitosan/polyethylene oxide nanofibers for bone tissue engineering.Journal of biomaterials science Polymer edition. 2020; 31: 781-803
- Modified electrospun chitosan membranes for controlled release of simvastatin.Int J Pharm. 2020; 584: 13
- Osteogenic induction of bone marrow mesenchymal cells on electrospun polycaprolactone/chitosan nanofibrous membrane.Dent Mater J. 2017; 36: 325-332
- Cellular behavior of L929 and MG-63 cells cultured on electrospun nanofibers of chitosan with different degrees of phosphorylation.Prog Biomater. 2016; 5: 93-100
- Polycaprolactone/carboxymethyl chitosan nanofibrous scaffolds for bone tissue engineering application.Int. J. Biol. Macromol. 2018; 115: 243-248
- Bone morphogenic protein-2 immobilization by cold atmospheric plasma to enhance the osteoinductivity of carboxymethyl chitosan-based nanofibers.Carbohydr Polym. 2020; 231: 9
- Electrospun metformin-loaded polycaprolactone/chitosan nanofibrous membranes as promoting guided bone regeneration membranes: preparation and characterization of fibers, drug release, and osteogenic activity in vitro.J Biomater Appl. 2020; 34: 282-1293
- A review of materials, fabrication methods, and strategies used to enhance bone regeneration in engineered bone tissues.J. Biomed. Mater. Res. 2008; : 573-582
- Dental pulp-derived stromal cells exhibit a higher osteogenic potency than bone marrow-derived stromal cells in vitro and in a porcine critical-size bone defect model.SICOT J. 2016; 2: 16
- Three dimensional printed macroporous polylactic acid/hydroxyapatite composite scaffolds for promoting bone formation in a critical-size rat calvarial defect model.Sci Technol Adv Mater. 2016; 8 (17): 136-148
- In vitro and in vivo bone formation potential of surface calcium phosphate-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds.Acta Biomater. 2016; 30: 319-333
- 3D biomimetic artificial bone scaffolds with dual-cytokines spatiotemporal delivery for large weight-bearing bone defect repair.Sci Rep. 2017; 7: 1-13
- Adhesion, proliferation and osteogenic differentiation of mesenchymal stem cells in 3D printed poly-ε-caprolactone/hydroxyapatite scaffolds combined with bone marrow clots.Mol Med Rep. 2017; 16: 5078-5084
Sun T. et al. Evaluation of osteogenic inductivity of a novel BMP 2-mimicking peptide P 28 and P 28-containing bone composite. 2018;106:210–20.
- Nano-biphasic calcium phosphate/polyvinyl alcohol composites with enhanced bioactivity for bone repair via low-temperature three-dimensional printing and loading with platelet-rich fibrin.Int J Nanomedicine. 2018; 13: 505-523
- Integrating 3D-printed PHBV/Calcium sulfate hemihydrate scaffold and chitosan hydrogel for enhanced osteogenic property.Carbohydrate polymer. 2018; 202: 106-114
- Use of a three-dimensional printed polylactide-coglycolide/tricalcium phosphate composite scaffold incorporating magnesium powder to enhance bone defect repair in rabbits.J Orthop Translat. 2019; 16: 62-70
- 3D-Printed Bioactive Calcium Silicate/Poly-ε-Caprolactone Bioscaffolds Modified with Biomimetic Extracellular Matrices for Bone Regeneration.Int. J. Mol. Sci. 2019; 942: 20
- Mesenchymal stem cell-loaded thermosensitive hydroxypropyl chitin hydrogel combined with a three-dimensional-printed poly (ε-caprolactone) /nano-hydroxyapatite scaffold to repair bone defects via osteogenesis, angiogenesis and immunomodulation.Theranostics. 2020; 10: 725-740
- Three dimensional printed polylactic acid-hydroxyapatite composite scaffolds for prefabricating vascularized tissue engineered bone: an in vivo bioreactor model.Sci Rep. 2017; 7: 15255
- Customized, degradable, functionally graded scaffold for potential treatment of early stage osteonecrosis of the femoral head.J Orthop Res. 2018; 36: 1002-1011
- Preclinical induced membrane model to evaluate synthetic implants for healing critical bone defects without autograft.Journal of orthopaedic research: official publication of the Orthopaedic Research Society. 2019; 37: 60-68
- A polycaprolactone-β-tricalcium phosphate-heparan sulphate device for cranioplasty.J Craniomaxillofac Surg. 2019; 47: 341-348
- The Characteristics of Mineral Trioxide Aggregate/Polycaprolactone 3-dimensional Scaffold with Osteogenesis Properties for Tissue Regeneration.J Endod. 2017; 43: 923-929
- Endothelial pattern formation in hybrid constructs of additive manufactured porous rigid scaffolds and cell-laden hydrogels for orthopedic applications.J Mech Behav Biomed Mater. 2017; 65: 356-372
- Enhanced biocompatibility and osteogenic potential of mesoporous magnesium silicate/polycaprolactone/wheat protein composite scaffolds.Int J Nanomedicine. 2018; 13: 1107-1117
Bruyas A. et al. Systematic characterization of 3D-printed PCL/β-TCP scaffolds for biomedical devices and bone tissue engineering: influence of composition and porosity. 2018;33:1948.
- Effect of Electron Beam Sterilization on Three-Dimensional-Printed Polycaprolactone/Beta-Tricalcium Phosphate Scaffolds for Bone Tissue Engineering.Tissue engineering Part A. 2019; 25: 248-256
- Calcium phosphates in biomedical applications: materials for the future?.Materials Today. 2016; 19: 69-87
- Reconstruction of Large Skeletal Defects: current Clinical Therapeutic Strategies and Future Directions Using 3D Printing.Frontier in Bioengineering and Biotechnology. 2021; 8: 11
- Engineering functionally graded tissue engineering scaffolds.J Mech Behav Biomed Mater. 2008; 1: 140-152
Article info
Publication history
Published online: February 15, 2022
Accepted:
February 11,
2022
Footnotes
This paper is part of a Supplement supported by the European Society of Tissue Regeneration in Orthopaedics and Traumatology (ESTROT).
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
