Poly (lactic acid)-based biomaterials for orthopaedic regenerative engineering

Advanced Drug Delivery Reviews - Tập 107 - Trang 247-276 - 2016
Ganesh Narayanan1,2,3, Varadraj N. Vernekar1,2,3, Emmanuel L. Kuyinu1,2,3, Cato T. Laurencin1,2,3,4,5,6,7,8
1Institute for Regenerative Engineering, University of Connecticut Health Center, Farmington, CT 06030, USA
2Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA
3Department of Orthopaedic Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA
4School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
5Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA
6Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA
7Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA
8Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA

Tài liệu tham khảo

Agarwal, 2015, Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair, Adv. Drug Deliv. Rev., 94, 53, 10.1016/j.addr.2015.03.013 Lee, 2008, Current state and future of joint replacements in the hip and knee, Expert Rev. Med. Devices, 5, 383, 10.1586/17434440.5.3.383 Chang, 2003, Anterior cruciate ligament reconstruction: allograft versus autograft, Arthroscopy, 19, 453, 10.1053/jars.2003.50103 Grood, 1976, Cruciate ligament prosthesis: strength, creep, and fatigue properties, J. Bone Joint Surg. Am., 58, 1083, 10.2106/00004623-197658080-00007 Mascarenhas, 2008, Anterior cruciate ligament reconstruction: a look at prosthetics-past, present and possible future, McGill J. Med., 11, 29 Laurencin, 1999, Tissue engineering: orthopedic applications, Annu. Rev. Biomed. Eng., 1, 19, 10.1146/annurev.bioeng.1.1.19 Shelton, 1997, Autograft versus allograft anterior cruciate ligament reconstruction, Arthroscopy, 13, 446, 10.1016/S0749-8063(97)90122-5 Ritchie, 1996, Graft selection in anterior cruciate ligament revision surgery, Clin. Orthop. Relat. Res., 325, 65, 10.1097/00003086-199604000-00008 Malinin, 2002, A study of retrieved allografts used to replace anterior cruciate ligaments, Arthroscopy, 18, 163, 10.1053/jars.2002.30485 Middleton, 2000, Synthetic biodegradable polymers as orthopedic devices, Biomaterials, 21, 2335, 10.1016/S0142-9612(00)00101-0 Nair, 2007, Biodegradable polymers as biomaterials, Prog. Polym. Sci., 32, 762, 10.1016/j.progpolymsci.2007.05.017 Nair, 2006, Polymers as biomaterials for tissue engineering and controlled drug delivery, 47 Madhavan Nampoothiri, 2010, An overview of the recent developments in polylactide (PLA) research, Bioresour. Technol., 101, 8493, 10.1016/j.biortech.2010.05.092 Migliaresi, 1991, The effect of thermal history on the crystallinity of different molecular weight PLLA biodegradable polymers, Clin. Mater., 8, 111, 10.1016/0267-6605(91)90018-B Lasprilla, 2012, Poly-lactic acid synthesis for application in biomedical devices—a review, Biotechnol. Adv., 30, 321, 10.1016/j.biotechadv.2011.06.019 Sarasua, 2005, Crystallinity and mechanical properties of optically pure polylactides and their blends, Polym. Eng. Sci., 45, 745, 10.1002/pen.20331 Perego, 1996, Effect of molecular weight and crystallinity on poly(lactic acid) mechanical properties, J. Appl. Polym. Sci., 59, 37, 10.1002/(SICI)1097-4628(19960103)59:1<37::AID-APP6>3.0.CO;2-N Yasuniwa, 2006, Crystallization behavior of poly(l-lactic acid), Polymer, 47, 7554, 10.1016/j.polymer.2006.08.054 Dell'Erba, 2001, Immiscible polymer blends of semicrystalline biocompatible components: thermal properties and phase morphology analysis of PLLA/PCL blends, Polymer, 42, 7831, 10.1016/S0032-3861(01)00269-5 Narayanan, 2014, Poly(ε-caprolactone) nanowebs functionalized with α- and γ-cyclodextrins, Biomacromolecules, 15, 4122, 10.1021/bm501158w Rangari, 2012, Study of strain-induced crystallization and enzymatic degradation of drawn poly(l-lactic acid) (PLLA) films, Macromolecules, 45, 7397, 10.1021/ma301482j Maurus, 2004, Bioabsorbable implant material review, Oper. Tech. Sports Med., 12, 158, 10.1053/j.otsm.2004.07.015 Makadia, 2011, Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier, Polymers, 3, 1377, 10.3390/polym3031377 Yu, 2012, Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly(lactic-co-glycolic acid), Drug Deliv. Transl. Res., 2, 124, 10.1007/s13346-011-0048-9 Cheng, 2009, Polylactic acid (PLA) synthesis and modifications: a review, Front. Chem. Chin., 4, 259, 10.1007/s11458-009-0092-x Ambrose, 2004, Bioabsorbable implants: review of clinical experience in orthopedic surgery, Ann. Biomed. Eng., 32, 171, 10.1023/B:ABME.0000007802.59936.fc Lim, 2008, Processing technologies for poly(lactic acid), Prog. Polym. Sci., 33, 820, 10.1016/j.progpolymsci.2008.05.004 Li, 2012, Preparation and characterization of PLLA/nHA nonwoven mats via laser melt electrospinning, Mater. Lett., 73, 103, 10.1016/j.matlet.2011.12.108 Gupta, 2007, Poly (lactic acid) fiber: an overview, Prog. Polym. Sci., 32, 455, 10.1016/j.progpolymsci.2007.01.005 Ge, 2005, Characterization of knitted polymeric scaffolds for potential use in ligament tissue engineering, J. Biomater. Sci. Polym. Ed., 16, 1179, 10.1163/1568562054798491 Zhao, 2010, Chondrogenic differentiation of stem cells in human umbilical cord stroma with PGA and PLLA scaffolds., J. Biomed. Sci. Eng., 3, 1041, 10.4236/jbise.2010.311135 Kuo, 2010, Novel strategies in tendon and ligament tissue engineering: Advanced biomaterials and regeneration motifs, Sports Med. Arthrosc. Rehabil. Ther. Technol., 2, 20 Tormala P, Rokkanen P, Laiho J, Tamminmaki M, Vainionpaa S Material for osteosynthesis devices. Google Patents; 1988. Juutilainen, 2002, Complications in the first 1043 operations where self-reinforced poly-l-lactide implants were used solely for tissue fixation in orthopaedics and traumatology, Int. Orthop. (SICOT), 26, 122, 10.1007/s00264-002-0332-x Li, 2008, Preparation of single poly(lactic acid) composites, J. Appl. Polym. Sci., 107, 2909, 10.1002/app.27406 Wu, 2013, Preparation and bending properties of three dimensional braided single poly (lactic acid) composite, Compos. B Eng., 52, 106, 10.1016/j.compositesb.2013.02.047 Gao, 2015, Preparation and characterization of uniaxial poly(lactic acid)-based self-reinforced composites, Compos. Sci. Technol., 117, 392, 10.1016/j.compscitech.2015.07.006 Charles, 2013, Self-reinforced composites of hydroxyapatite-coated PLLA fibers: fabrication and mechanical characterization, J. Mech. Behav. Biomed. Mater., 17, 269, 10.1016/j.jmbbm.2012.09.007 Chen, 2015, Comparison and preparation of multilayered polylactic acid fabric strengthen calcium phosphate-based bone substitutes for orthopedic applications, J. Artif. Organs Ella, 2005, In vitro properties of PLLA screws and novel bioabsorbable implant with elastic nucleus to replace intervertebral disc, J. Mater. Sci. Mater. Med., 16, 655, 10.1007/s10856-005-2537-1 Veiranto, 2002, In vitro mechanical and drug release properties of bioabsorbable ciprofloxacin containing and neat self-reinforced P(L/DL)LA 70/30 fixation screws, J. Mater. Sci. Mater. Med., 13, 1259, 10.1023/A:1021187331458 Torres-Giner, 2012, Controlled delivery of gentamicin antibiotic from bioactive electrospun polylactide-based ultrathin fibers, Adv. Eng. Mater., 14, 10.1002/adem.201180006 Laurencin, 1993, Bioerodible polyanhydrides for antibiotic drug delivery: in vivo osteomyelitis treatment in a rat model system, J. Orthop. Res., 11, 256, 10.1002/jor.1100110213 Baro, 2002, In vitro–in vivo characterization of gentamicin bone implants, J. Control. Release, 83, 353, 10.1016/S0168-3659(02)00179-7 Shah, 2013, Evolving strategies for preventing biofilm on implantable materials, Mater. Today, 16, 177, 10.1016/j.mattod.2013.05.003 Danoux, 2014, In vitro and in vivo bioactivity assessment of a polylactic acid/hydroxyapatite composite for bone regeneration, Biomatter, 4, 10.4161/biom.27664 Simpson, 2015, A comparative study of the effects of different bioactive fillers in PLGA matrix composites and their suitability as bone substitute materials: a thermo-mechanical and in vitro investigation, J. Mech. Behav. Biomed. Mater., 50, 277, 10.1016/j.jmbbm.2015.06.008 Giordano, 1997, Mechanical properties of dense polylactic acid structures fabricated by three dimensional printing, J. Biomater. Sci. Polym. Ed., 8, 63, 10.1163/156856297X00588 Farahani, 2014, Three-dimensional printing of freeform helical microstructures: a review, Nanoscale, 6, 10470, 10.1039/C4NR02041C Guo, 2013, Solvent-cast three-dimensional printing of multifunctional microsystems, Small, 9, 4118, 10.1002/smll.201300975 Hollister, 2005, Porous scaffold design for tissue engineering, Nat. Mater., 4, 518, 10.1038/nmat1421 Vásquez Quintero, 2014, Printing and Encapsulation of Electrical Conductors on Polylactic Acid (PLA) for Sensing Applications. Micro Electro Mechanical Systems (MEMS), 532 Xiong, 2002, Fabrication of porous scaffolds for bone tissue engineering via low-temperature deposition, Scr. Mater., 46, 771, 10.1016/S1359-6462(02)00071-4 Yan, 2003, Layered manufacturing of tissue engineering scaffolds via multi-nozzle deposition, Mater. Lett., 57, 2623, 10.1016/S0167-577X(02)01339-3 Yan, 2005, Fabrication of viable tissue-engineered constructs with 3D cell-assembly technique, Biomaterials, 26, 5864, 10.1016/j.biomaterials.2005.02.027 Shaffer, 2014, On reducing anisotropy in 3D printed polymers via ionizing radiation, Polymer, 55, 5969, 10.1016/j.polymer.2014.07.054 Senatov, 2016, Mechanical properties and shape memory effect of 3D-printed PLA-based porous scaffolds, J. Mech. Behav. Biomed. Mater., 57, 139, 10.1016/j.jmbbm.2015.11.036 Ogden, 2014, Dimensional accuracy of3D printed vertebra, 903629 Sherwood, 2002, A three-dimensional osteochondral composite scaffold for articular cartilage repair, Biomaterials, 23, 4739, 10.1016/S0142-9612(02)00223-5 Narayanan, 2015, Enhanced mechanical properties of poly (ε-caprolactone) nanofibers produced by the addition of non-stoichiometric inclusion complexes of poly (ε-caprolactone) and α-cyclodextrin, Polymer, 76, 321, 10.1016/j.polymer.2015.08.045 Narayanan, 2015, Efficient wound odor removal by β-cyclodextrin functionalized poly (ε-caprolactone) nanofibers, J. Appl. Polym. Sci., 132, 10.1002/app.42782 Jiang, 2015, Electrospinning of polymer nanofibers for tissue regeneration, Prog. Polym. Sci., 46, 1, 10.1016/j.progpolymsci.2014.12.001 Nair, 2004, Development of novel tissue engineering scaffolds via electrospinning, Expert. Opin. Biol. Ther., 4, 659, 10.1517/14712598.4.5.659 Yarin, 2001, Bending instability in electrospinning of nanofibers, J. Appl. Phys., 89, 3018, 10.1063/1.1333035 Arras, 2012, Electrospinning of aligned fibers with adjustable orientation using auxiliary electrodes, Sci. Technol. Adv. Mater., 13, 035008, 10.1088/1468-6996/13/3/035008 Zamani, 2013, The influence of surface nanoroughness of electrospun PLGA nanofibrous scaffold on nerve cell adhesion and proliferation, J. Mater. Sci. Mater. Med., 24, 1551, 10.1007/s10856-013-4905-6 Santos, 2013, Electrospun membranes of poly (lactic acid)(PLA) used as scaffold in drug delivery of extract of Sedum dendroideum, J. Nanosci. Nanotechnol., 13, 4694, 10.1166/jnn.2013.7194 Kim, 2006, Electrospinning biomedical nanocomposite fibers of hydroxyapatite/poly (lactic acid) for bone regeneration, J. Biomed. Mater. Res. A, 79, 643, 10.1002/jbm.a.30866 Cao, 2012, Degradation and osteogenic potential of a novel poly (lactic acid)/nano-sized β-tricalcium phosphate scaffold, Int. J. Nanomedicine, 7, 5881, 10.2147/IJN.S38127 Llorens, 2015, Polybiguanide (PHMB) loaded in PLA scaffolds displaying high hydrophobic, biocompatibility and antibacterial properties, Mater. Sci. Eng. C, 50, 74, 10.1016/j.msec.2015.01.100 Wang, 2013, Preparation and optimization of silver nanoparticles embedded electrospun membrane for implant associated infections prevention, ACS Appl. Mater. Interfaces, 5, 11014, 10.1021/am403250t Katti, 2004, Bioresorbable nanofiber-based systems for wound healing and drug delivery: optimization of fabrication parameters, J. Biomed. Mater. Res. B Appl. Biomater., 70B, 286, 10.1002/jbm.b.30041 Greiner, 2007, Electrospinning: a fascinating method for the preparation of ultrathin fibers, Angew. Chem. Int. Ed., 46, 5670, 10.1002/anie.200604646 Li, 2002, Electrospun nanofibrous structure: a novel scaffold for tissue engineering, J. Biomed. Mater. Res., 60, 613, 10.1002/jbm.10167 Bhattacharyya, 2009, Biodegradable polyphosphazene–nanohydroxyapatite composite nanofibers: scaffolds for bone tissue engineering, J. Biomed. Nanotechnol., 5, 69, 10.1166/jbn.2009.032 Aviss, 2010, Aligned electrospun polymer fibres for skeletal muscle regeneration, Eur. Cell. Mater., 19, 193, 10.22203/eCM.v019a19 Kumbar, 2008, Electrospun nanofiber scaffolds: engineering soft tissues, Biomed Mater., 3, 034002, 10.1088/1748-6041/3/3/034002 James, 2011, Electrospun nanofibrous scaffolds for engineering soft connective tissues, 243 Taylor, 2010, Novel nanostructured scaffolds as therapeutic replacement options for rotator cuff disease, J. Bone Joint Surg., 92, 170, 10.2106/JBJS.J.01112 Kumbar, 2008, Electrospun poly(lactic acid-co-glycolic acid) scaffolds for skin tissue engineering, Biomaterials, 29, 4100, 10.1016/j.biomaterials.2008.06.028 James, 2011, Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems, Biomed. Mater., 6, 025011, 10.1088/1748-6041/6/2/025011 Detta, 2010, Melt electrospinning of polycaprolactone and its blends with poly(ethylene glycol), Polym. Int., 59, 1558, 10.1002/pi.2954 Larrondo, 1981, Electrostatic fiber spinning from polymer melts. III. Electrostatic deformation of a pendant drop of polymer melt, J. Polym. Sci. Polym. Phys. Ed., 19, 933, 10.1002/pol.1981.180190603 Lyons, 2004, Melt-electrospinning part I: processing parameters and geometric properties, Polymer, 45, 7597, 10.1016/j.polymer.2004.08.071 Brown, 2016, Melt electrospinning today: an opportune time for an emerging polymer process., Prog. Polym. Sci., 56, 116, 10.1016/j.progpolymsci.2016.01.001 Zhou, 2006, The thermal effects on electrospinning of polylactic acid melts, Polymer, 47, 7497, 10.1016/j.polymer.2006.08.042 Zhao, 2012, Orthogonal design study on factors affecting the degradation of polylactic acid fibers of melt electrospinning, J. Appl. Polym. Sci., 125, 2652, 10.1002/app.36426 Yoon, 2013, Fabrication of microfibrous and nano-/microfibrous scaffolds: melt and hybrid electrospinning and surface modification of poly(l-lactic acid) with plasticizer, BioMed Res. Int., 2013, 10, 10.1155/2013/309048 Ogata, 2007, Poly(lactide) nanofibers produced by a melt-electrospinning system with a laser melting device, J. Appl. Polym. Sci., 104, 1640, 10.1002/app.25782 Muerza-Cascante, 2014, Melt electrospinning and its technologization in tissue engineering, Tissue Eng. Part B Rev., 21, 187, 10.1089/ten.teb.2014.0347 Bas, 2015, Enhancing structural integrity of hydrogels by using highly organised melt electrospun fibre constructs, Eur. Polym. J., 72, 451, 10.1016/j.eurpolymj.2015.07.034 Woodruff, 2010, The return of a forgotten polymer—polycaprolactone in the 21st century, Prog. Polym. Sci., 35, 1217, 10.1016/j.progpolymsci.2010.04.002 Brown, 2011, Direct writing by way of melt electrospinning, Adv. Mater., 23, 5651, 10.1002/adma.201103482 Brooke, 2013, Dermal fibroblast infiltration of poly(ε-caprolactone) scaffolds fabricated by melt electrospinning in a direct writing mode, Biofabrication, 5, 025001, 10.1088/1758-5082/5/2/025001 Paul, 2008, Patterned melt electrospun substrates for tissue engineering, Biomed. Mater., 3, 034109, 10.1088/1748-6041/3/3/034109 Brown, 2012, Design and fabrication of tubular scaffolds via direct writing in a melt electrospinning mode, Biointerphases, 7, 13, 10.1007/s13758-011-0013-7 Jungst, 2015, Melt electrospinning onto cylinders: effects of rotational velocity and collector diameter on morphology of tubular structures, Polym. Int., 64, 1086, 10.1002/pi.4948 Brown, 2014, Melt electrospinning of poly(ε-caprolactone) scaffolds: phenomenological observations associated with collection and direct writing, Mater. Sci. Eng. C, 45, 698, 10.1016/j.msec.2014.07.034 Qin, 2015, Melt electrospinning of poly(lactic acid) and polycaprolactone microfibers by using a hand-operated Wimshurst generator, Nanoscale, 7, 16611, 10.1039/C5NR05367F Reis, 2006, Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles, Nanomedicine, 2, 8, 10.1016/j.nano.2005.12.003 Vauthier, 2009, Methods for the preparation and manufacture of polymeric nanoparticles, Pharm. Res., 26, 1025, 10.1007/s11095-008-9800-3 Mosqueira, 2001, Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules, Biomaterials, 22, 2967, 10.1016/S0142-9612(01)00043-6 James, 2011, Nanocomposites and bone regeneration, Front. Mater. Sci., 5, 342, 10.1007/s11706-011-0151-3 Hu, 2013, Glioma therapy using tumor homing and penetrating peptide-functionalized PEG–PLA nanoparticles loaded with paclitaxel, Biomaterials, 34, 5640, 10.1016/j.biomaterials.2013.04.025 Panyam, 2003, Biodegradable nanoparticles for drug and gene delivery to cells and tissue, Adv. Drug Deliv. Rev., 55, 329, 10.1016/S0169-409X(02)00228-4 Mohanraj, 2007, Nanoparticles—a review, Trop. J. Pharm. Res., 5, 561, 10.4314/tjpr.v5i1.14634 Avgoustakis, 2004, Pegylated poly (lactide) and poly (lactide-co-glycolide) nanoparticles: preparation, properties and possible applications in drug delivery, Curr. Drug Deliv., 1, 321, 10.2174/1567201043334605 Babu, 2014, Chitosan coated polylactic acid nanoparticle-mediated combinatorial delivery of cisplatin and siRNA/plasmid DNA chemosensitizes cisplatin-resistant human ovarian cancer cells, Mol. Pharm., 11, 2720, 10.1021/mp500259e Verma, 2012, Size-tunable nanoparticles composed of dextran-b-poly (d,l-lactide) for drug delivery applications, Nano Res., 5, 49, 10.1007/s12274-011-0184-z Santander-Ortega, 2006, Colloidal stability of pluronic F68-coated PLGA nanoparticles: a variety of stabilisation mechanisms, J. Colloid Interface Sci., 302, 522, 10.1016/j.jcis.2006.07.031 Ren, 2009, Preparation and therapeutic efficacy of polysorbate-80-coated amphotericin B/PLA-b-PEG nanoparticles, J. Biomater. Sci. Polym. Ed., 20, 1369, 10.1163/092050609X12457418779185 Nobs, 2003, Surface modification of poly (lactic acid) nanoparticles by covalent attachment of thiol groups by means of three methods, Int. J. Pharm., 250, 327, 10.1016/S0378-5173(02)00542-2 Amoozgar, 2012, Recent advances in stealth coating of nanoparticle drug delivery systems, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 4, 219, 10.1002/wnan.1157 Jain, 2014, Surface-coated PLA nanoparticles loaded with temozolomide for improved brain deposition and potential treatment of gliomas: development, characterization and in vivo studies, Drug Deliv., 1-18, 10.1007/978-1-4939-0363-4 Yu, 2012, PLA-based nanoparticles with tunable hydrophobicity and degradation kinetics, J. Polym. Sci. A Polym. Chem., 50, 5191, 10.1002/pola.26370 Moorkoth, 2014, Synthesis, colloidal properties and cytotoxicity of biopolymer nanoparticles, Appl. Biochem. Biotechnol., 174, 2181, 10.1007/s12010-014-1172-z Valo, 2009, Electrospray encapsulation of hydrophilic and hydrophobic drugs in poly (l-lactic acid) nanoparticles, Small, 5, 1791, 10.1002/smll.200801907 O'Brien, 2011, Biomaterials and scaffolds for tissue engineering, Mater. Today, 14, 88, 10.1016/S1369-7021(11)70058-X Laurencin, 2013 Laurencin, 2015, Regenerative engineering: approaches to limb regeneration and other grand challenges, Regen. Eng. Transl. Med., 1, 1, 10.1007/s40883-015-0006-z Laurencin, 2012, Regenerative engineering, Sci. Transl. Med., 4, 160ed9, 10.1126/scitranslmed.3004467 Wang, 2013, Role of mesenchymal stem cells in bone regeneration and fracture repair: a review, Int. Orthop. (SICOT), 37, 2491, 10.1007/s00264-013-2059-2 Pipino, 2015, Osteogenic differentiation of amniotic fluid mesenchymal stromal cells and their bone regeneration potential, World J. Stem Cells, 7, 681, 10.4252/wjsc.v7.i4.681 Kasir, 2015, Regenerative engineering of cartilage using adipose-derived stem cells, Regen. Eng. Transl. Med., 1, 42, 10.1007/s40883-015-0005-0 Copp, 1963, The homeostatic function of bone as a mineral reservoir, Oral Surg. Oral Med. Oral Pathol., 16, 738, 10.1016/0030-4220(63)90081-1 Venkatesan, 2015, Alginate composites for bone tissue engineering: a review, Int. J. Biol. Macromol., 72, 269, 10.1016/j.ijbiomac.2014.07.008 Stevens, 2008, Biomaterials for bone tissue engineering, Mater. Today, 11, 18, 10.1016/S1369-7021(08)70086-5 Ma, 2001, Engineering new bone tissue in vitro on highly porous poly (α-hydroxyl acids)/hydroxyapatite composite scaffolds, J. Biomed. Mater. Res., 54, 284, 10.1002/1097-4636(200102)54:2<284::AID-JBM16>3.0.CO;2-W Sheikh, 2015, Biodegradable materials for bone repair and tissue engineering applications, Materials, 8, 5744, 10.3390/ma8095273 Mackie, 2008, Endochondral ossification: how cartilage is converted into bone in the developing skeleton, Int. J. Biochem. Cell Biol., 40, 46, 10.1016/j.biocel.2007.06.009 Amini, 2012, Bone tissue engineering: recent advances and challenges, Crit. Rev. Biomed. Eng., 40, 363, 10.1615/CritRevBiomedEng.v40.i5.10 Laurencin, 2006, Bone graft substitutes, Expert Rev. Med. Devices, 3, 49, 10.1586/17434440.3.1.49 Deng, 2011, Novel polymer-ceramics for bone repair and regeneration, Recent Patents Biomed. Eng., 4, 168, 10.2174/1874764711104030168 Keogh, 2010, A novel collagen scaffold supports human osteogenesis—applications for bone tissue engineering, Cell Tissue Res., 340, 169, 10.1007/s00441-010-0939-y López-Álvarez, 2013, Bio-inspired ceramics: promising scaffolds for bone tissue engineering, Procedia Eng., 59, 51, 10.1016/j.proeng.2013.05.093 Lin, 2002, Preparation of macroporous biodegradable PLGA scaffolds for cell attachment with the use of mixed salts as porogen additives, J. Biomed. Mater. Res., 63, 271, 10.1002/jbm.10183 Nanda, 2014, Collagen microgel-assisted dexamethasone release from PLLA-collagen hybrid scaffolds of controlled pore structure for osteogenic differentiation of mesenchymal stem cells, J. Biomater. Sci. Polym. Ed., 25, 1374, 10.1080/09205063.2014.938980 Vaquette, 2008, An innovative method to obtain porous PLLA scaffolds with highly spherical and interconnected pores, J. Biomed. Mater. Res. B Appl. Biomater., 86, 9, 10.1002/jbm.b.30982 Zhang, 2011, RGD-conjugated copolymer incorporated into composite of poly (lactide-co-glycotide) and poly (l-lactide)-grafted nanohydroxyapatite for bone tissue engineering, Biomacromolecules, 12, 2667, 10.1021/bm2004725 Zhao, 2011, Improved biocompatibility of novel poly (l-lactic acid)/β-tricalcium phosphate scaffolds prepared by an organic solvent-free method, Int. J. Nanomedicine, 6, 1385 Zhang, 2009, In vivo mineralization and osteogenesis of nanocomposite scaffold of poly (lactide-co-glycolide) and hydroxyapatite surface-grafted with poly (l-lactide), Biomaterials, 30, 58, 10.1016/j.biomaterials.2008.08.041 Cui, 2015, A novel nano/micro-fibrous scaffold by melt-spinning method for bone tissue engineering, J. Bionic Eng., 12, 117, 10.1016/S1672-6529(14)60106-2 Qu, 2013, Physical modification of the interior surfaces of PLGA porous scaffolds using sugar fibers as template, J. Biomater. Sci. Polym. Ed., 24, 447, 10.1080/09205063.2012.690285 Brady, 2015, Development of composite poly (lactide-co-glycolide)-nanodiamond scaffolds for bone cell growth, J. Nanosci. Nanotechnol., 15, 1060, 10.1166/jnn.2015.9745 Luo, 2015, Enhanced proliferation and osteogenic differentiation of mesenchymal stem cells on graphene oxide-incorporated electrospun poly (lactic-co-glycolic acid) nanofibrous mats, ACS Appl. Mater. Interfaces, 7, 6331, 10.1021/acsami.5b00862 Zhou, 2014, Organic/inorganic composite membranes based on poly (L-lactic-co-glycolic acid) and mesoporous silica for effective bone tissue engineering, ACS Appl. Mater. Interfaces, 6, 20895, 10.1021/am505493j Samavedi, 2014, Electrospun meshes possessing region-wise differences in fiber orientation, diameter, chemistry and mechanical properties for engineering bone–ligament–bone tissues, Biotechnol. Bioeng., 111, 2549, 10.1002/bit.25299 Jamshidi Adegani, 2014, Coating of electrospun poly (lactic-co-glycolic acid) nanofibers with willemite bioceramic: improvement of bone reconstruction in rat model, Cell Biol. Int., 38, 1271, 10.1002/cbin.10318 Nelson, 2014, Nanofiber–microsphere (nano-micro) matrices for bone regenerative engineering: a convergence approach toward matrix design, Regen. Biomater., 1, 3, 10.1093/rb/rbu002 Privalova, 2015, Biodegradable polyester-based microcarriers with modified surface tailored for tissue engineering, J. Biomed. Mater. Res. A, 103, 939, 10.1002/jbm.a.35231 Selcan Gungor-Ozkerim, 2014, Incorporation of growth factor loaded microspheres into polymeric electrospun nanofibers for tissue engineering applications, J. Biomed. Mater. Res. A, 102, 1897, 10.1002/jbm.a.34857 Xin-Hui, 2010, Structural and degradation characteristics of an innovative porous PLGA/TCP scaffold incorporated with bioactive molecular icaritin, Biomed. Mater., 5, 054109, 10.1088/1748-6041/5/5/054109 Roy, 2003, Performance of degradable composite bone repair products made via three-dimensional fabrication techniques, J. Biomed. Mater. Res. A, 66, 283, 10.1002/jbm.a.10582 Castro, 2015, Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds, Nanoscale, 7, 14010, 10.1039/C5NR03425F Nakagawa, 2006, Improvement of cell adhesion on poly (l-lactide) by atmospheric plasma treatment, J. Biomed. Mater. Res. A, 77, 112, 10.1002/jbm.a.30521 Woo, 2007, Suppression of apoptosis by enhanced protein adsorption on polymer/hydroxyapatite composite scaffolds, Biomaterials, 28, 2622, 10.1016/j.biomaterials.2007.02.004 Ma, 2003, Paraffin spheres as porogen to fabricate poly(l-lactic acid) scaffolds with improved cytocompatibility for cartilage tissue engineering, J. Biomed. Mater. Res. B Appl. Biomater., 67, 610, 10.1002/jbm.b.10049 Gong, 2008, Poly (lactic acid) scaffold fabricated by gelatin particle leaching has good biocompatibility for chondrogenesis, J. Biomater. Sci. Polym. Ed., 19, 207, 10.1163/156856208783432453 Liao, 2002, Fabrication of porous biodegradable polymer scaffolds using a solvent merging/particulate leaching method, J. Biomed. Mater. Res., 59, 676, 10.1002/jbm.10030 Liu, 2004, Polymeric scaffolds for bone tissue engineering, Ann. Biomed. Eng., 32, 477, 10.1023/B:ABME.0000017544.36001.8e Maquet, 2004, Porous poly (α-hydroxyacid)/bioglass® composite scaffolds for bone tissue engineering. I: preparation and in vitro characterisation, Biomaterials, 25, 4185, 10.1016/j.biomaterials.2003.10.082 Ahmadi, 2011, Enhanced attachment, growth and migration of smooth muscle cells on microcarriers produced using thermally induced phase separation, Acta Biomater., 7, 1542, 10.1016/j.actbio.2010.12.022 Salerno, 2014, Macroporous and nanometre scale fibrous PLA and PLA–HA composite scaffolds fabricated by a bio safe strategy, RSC Adv., 4, 61491, 10.1039/C4RA07732F Kim, 2006, Poly (lactide-co-glycolide)/hydroxyapatite composite scaffolds for bone tissue engineering, Biomaterials, 27, 1399, 10.1016/j.biomaterials.2005.08.016 Mooney, 1996, Novel approach to fabricate porous sponges of poly(d,l-lactic-co-glycolic acid) without the use of organic solvents, Biomaterials, 17, 1417, 10.1016/0142-9612(96)87284-X Mikos, 2000 Narayanan, 2015, Fabrication and characterization of poly (ε-caprolactone)/α-cyclodextrin pseudorotaxane nanofibers, Biomacromolecules Sahoo, 2010, Growth factor delivery through electrospun nanofibers in scaffolds for tissue engineering applications, J. Biomed. Mater. Res. A, 93, 1539 Zhao, 2015, Nitrofurazone-loaded electrospun PLLA/sericin-based dual-layer fiber mats for wound dressing applications, RSC Adv., 5, 16940, 10.1039/C4RA16208K Tuzlakoglu, 2005, Nano- and micro-fiber combined scaffolds: a new architecture for bone tissue engineering, J. Mater. Sci. Mater. Med., 16, 1099, 10.1007/s10856-005-4713-8 Whited, 2011, Pre-osteoblast infiltration and differentiation in highly porous apatite-coated PLLA electrospun scaffolds, Biomaterials, 32, 2294, 10.1016/j.biomaterials.2010.12.003 Boskey, 1996, Matrix proteins and mineralization: an overview, Connect. Tissue Res., 35, 357, 10.3109/03008209609029212 Cui, 2010, Hydroxyapatite nucleation and growth mechanism on electrospun fibers functionalized with different chemical groups and their combinations, Biomaterials, 31, 4620, 10.1016/j.biomaterials.2010.02.050 Dinarvand, 2011, New approach to bone tissue engineering: simultaneous application of hydroxyapatite and bioactive glass coated on a poly(l-lactic acid) scaffold, ACS Appl. Mater. Interfaces, 3, 4518, 10.1021/am201212u Andric, 2015, Fabrication and characterization of three-dimensional electrospun scaffolds for bone tissue engineering, Regen. Eng. Transl. Med., 1, 32, 10.1007/s40883-015-0004-1 Andric, 2012, Fabrication and characterization of three-dimensional electrospun scaffolds for bone tissue engineering, J. Biomed. Mater. Res. A, 100, 2097, 10.1002/jbm.a.34045 Brown, 2010, Composite scaffolds: bridging nanofiber and microsphere architectures to improve bioactivity of mechanically competent constructs, J. Biomed. Mater. Res. A, 95A, 1150, 10.1002/jbm.a.32934 Borden, 2004, Tissue-engineered bone formation in vivo using a novel sintered polymeric microsphere matrix, J. Bone Joint Surg. Br. Vol., 86-B, 1200, 10.1302/0301-620X.86B8.14267 Shen, 2006, Osteogenic differentiation of adipose-derived stromal cells treated with GDF-5 cultured on a novel three-dimensional sintered microsphere matrix, Spine J., 6, 615, 10.1016/j.spinee.2006.03.006 Lv, 2009, Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano-hydroxyapatite composite microsphere-based scaffolds for bone tissue engineering in rotating bioreactors, J. Biomed. Mater. Res. A, 91A, 679, 10.1002/jbm.a.32302 Lu, 2003, Three-dimensional, bioactive, biodegradable, polymer–bioactive glass composite scaffolds with improved mechanical properties support collagen synthesis and mineralization of human osteoblast-like cells in vitro, J. Biomed. Mater. Res. A, 64A, 465, 10.1002/jbm.a.10399 Cushnie, 2008, Amorphous hydroxyapatite-sintered polymeric scaffolds for bone tissue regeneration: physical characterization studies, J. Biomed. Mater. Res. A, 84A, 54, 10.1002/jbm.a.31380 Borden, 2002, The sintered microsphere matrix for bone tissue engineering: in vitro osteoconductivity studies, J. Biomed. Mater. Res., 61, 421, 10.1002/jbm.10201 Jabbarzadeh, 2012, VEGF-incorporated biomimetic poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering, J. Biomed. Mater. Res. B Appl. Biomater., 100B, 2187, 10.1002/jbm.b.32787 Amini, 2012, Optimally porous and biomechanically compatible scaffolds for large-area bone regeneration, Tissue Eng. A, 18, 1376, 10.1089/ten.tea.2011.0076 Jiang, 2006, In vitro evaluation of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds for bone tissue engineering, Biomaterials, 27, 4894, 10.1016/j.biomaterials.2006.05.025 Brown, 2008, Solvent/non-solvent sintering: a novel route to create porous microsphere scaffolds for tissue regeneration, J. Biomed. Mater. Res. B Appl. Biomater., 86B, 396, 10.1002/jbm.b.31033 Abdel-Fattah, 2007, Synthesis, characterization of chitosans and fabrication of sintered chitosan microsphere matrices for bone tissue engineering, Acta Biomater., 3, 503, 10.1016/j.actbio.2006.12.004 Khan, 2008, Tissue engineering of bone: material and matrix considerations, J. Bone Joint Surg., 90, 36, 10.2106/JBJS.G.01260 Jiang, 2010, Chitosan–poly(lactide-co-glycolide) microsphere-based scaffolds for bone tissue engineering: in vitro degradation and in vivo bone regeneration studies, Acta Biomater., 6, 3457, 10.1016/j.actbio.2010.03.023 Aravamudhan, 2013, Cellulose and collagen derived micro-nano structured scaffolds for bone tissue engineering, J. Biomed. Nanotechnol., 9, 719, 10.1166/jbn.2013.1574 Kofron, 2007, Novel tubular composite matrix for bone repair, J. Biomed. Mater. Res. A, 82A, 415, 10.1002/jbm.a.31148 Borden, 2003, Structural and human cellular assessment of a novel microsphere-based tissue engineered scaffold for bone repair, Biomaterials, 24, 597, 10.1016/S0142-9612(02)00374-5 Nukavarapu, 2011, Optimal scaffold design and effective progenitor cell identification for the regeneration of vascularized bone, 2464 Amini, 2014, Oxygen-tension controlled matrices for enhanced osteogenic cell survival and performance, Ann. Biomed. Eng., 42, 1261, 10.1007/s10439-014-0990-z Verma, 2010, Effect of biomimetic 3D environment of an injectable polymeric scaffold on MG-63 osteoblastic-cell response, Mater. Sci. Eng. C, 30, 1118, 10.1016/j.msec.2010.06.005 Serra, 2013, High-resolution PLA-based composite scaffolds via 3-D printing technology, Acta Biomater., 9, 5521, 10.1016/j.actbio.2012.10.041 Yang, 2006, Nanomachining by colloidal lithography, Small, 2, 458, 10.1002/smll.200500390 Dalby, 2007, The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder, Nat. Mater., 6, 997, 10.1038/nmat2013 Fukada, 1957, On the piezoelectric effect of bone, J. Phys. Soc. Jpn., 12, 1158, 10.1143/JPSJ.12.1158 Blank, 1997, Do electromagnetic fields interact directly with DNA?, Bioelectromagnetics, 18, 111, 10.1002/(SICI)1521-186X(1997)18:2<111::AID-BEM3>3.0.CO;2-5 Cao, 2013, Electrical stimuli improve osteogenic differentiation mediated by aniline pentamer and PLGA nanocomposites, Biomed. Rep., 1, 428, 10.3892/br.2013.70 Bagchi, 2014, Perovskite ceramic nanoparticles in polymer composites for augmenting bone tissue regeneration, Nanotechnology, 25, 485101, 10.1088/0957-4484/25/48/485101 Zhang, 2016, The surface grafting of graphene oxide with poly(ethylene glycol) as a reinforcement for poly(lactic acid) nanocomposite scaffolds for potential tissue engineering applications, J. Mech. Behav. Biomed. Mater., 53, 403, 10.1016/j.jmbbm.2015.08.043 Paiyz, 2014, Functionalized carbon nanotube reinforced scaffolds for bone regenerative engineering: fabrication, in vitro and in vivo evaluation, Biomed. Mater., 9, 035001, 10.1088/1748-6041/9/3/035001 Lahiri, 2010, Boron nitride nanotube reinforced polylactide-polycaprolactone copolymer composite: mechanical properties and cytocompatibility with osteoblasts and macrophages in vitro, Acta Biomater., 6, 3524, 10.1016/j.actbio.2010.02.044 Li, 2015, Boron nitride nanotube-enhanced osteogenic differentiation of mesenchymal stem cells, J. Biomed. Mater. Res. B Appl. Biomater. Lakhkar, 2013, Bone formation controlled by biologically relevant inorganic ions: role and controlled delivery from phosphate-based glasses, Adv. Drug Deliv. Rev., 65, 405, 10.1016/j.addr.2012.05.015 Hickey, 2015, Adding MgO nanoparticles to hydroxyapatite-PLLA nanocomposites for improved bone tissue engineering applications, Acta Biomater., 14, 175, 10.1016/j.actbio.2014.12.004 Stevanovic, 2015, 45S5Bioglass(R)-based scaffolds coated with selenium nanoparticles or with poly(lactide-co-glycolide)/selenium particles: processing, evaluation and antibacterial activity, Colloids Surf. B: Biointerfaces, 132, 208, 10.1016/j.colsurfb.2015.05.024 Shameli, 2010, Silver/poly (lactic acid) nanocomposites: preparation, characterization, and antibacterial activity, Int. J. Nanomedicine, 5, 573, 10.2147/IJN.S12007 Stolzoff, 2015, Reducing bone cancer cell functions using selenium nanocomposites, J. Biomed. Mater. Res. A Gerstenfeld, 2003, Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation, J. Cell. Biochem., 88, 873, 10.1002/jcb.10435 Dimitriou, 2005, Current concepts of molecular aspects of bone healing., Injury, 36, 1392, 10.1016/j.injury.2005.07.019 Phillips, 2005, Overview of the fracture healing cascade., Injury, 36, S5, 10.1016/j.injury.2005.07.027 Marsell, 2011, The biology of fracture healing, Injury, 42, 551, 10.1016/j.injury.2011.03.031 Lu, 2003, In vitro bone formation using muscle-derived cells: a new paradigm for bone tissue engineering using polymer–bone morphogenetic protein matrices, Biochem. Biophys. Res. Commun., 305, 882, 10.1016/S0006-291X(03)00858-1 Lo, 2012, Studies of bone morphogenetic protein-based surgical repair, Adv. Drug Deliv. Rev., 64, 1277, 10.1016/j.addr.2012.03.014 Schofer, 2011, Electrospun PLLA nanofiber scaffolds and their use in combination with BMP-2 for reconstruction of bone defects, PLoS One, 6, 10.1371/journal.pone.0025462 Valdes, 2009, Recombinant bone morphogenic protein-2 in orthopaedic surgery: a review, Arch. Orthop. Trauma Surg., 129, 1651, 10.1007/s00402-009-0850-8 Cushnie, 2014, Simple signaling molecules for inductive bone regenerative engineering, PLoS One, 9, 10.1371/journal.pone.0101627 Su, 2012, Controlled release of bone morphogenetic protein 2 and dexamethasone loaded in core-shell PLLACL-collagen fibers for use in bone tissue engineering, Acta Biomater., 8, 763, 10.1016/j.actbio.2011.11.002 Yang, 2008, Structural stability and release profiles of proteins from core-shell poly (dl-lactide) ultrafine fibers prepared by emulsion electrospinning, J. Biomed. Mater. Res. A, 86A, 374, 10.1002/jbm.a.31595 Shah, 2014, Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction, Proc. Natl. Acad. Sci., 111, 12847, 10.1073/pnas.1408035111 Ku, 2010, General functionalization route for cell adhesion on non-wetting surfaces, Biomaterials, 31, 2535, 10.1016/j.biomaterials.2009.12.020 Shin, 2012, Mussel-inspired immobilization of vascular endothelial growth factor (VEGF) for enhanced endothelialization of vascular grafts, Biomacromolecules, 13, 2020, 10.1021/bm300194b Vo, 2012, Strategies for controlled delivery of growth factors and cells for bone regeneration, Adv. Drug Deliv. Rev., 64, 1292, 10.1016/j.addr.2012.01.016 Carbone, 2014, Regulation of bone regeneration with approved small molecule compounds, Adv. Regen. Biol., 1 Lo, 2014, Small-molecule based musculoskeletal regenerative engineering, Trends Biotechnol., 32, 74, 10.1016/j.tibtech.2013.12.002 Kato, 2011, A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype, Mol. Cell. Biochem., 349, 97, 10.1007/s11010-010-0664-6 Lo, 2014, Evaluating the feasibility of utilizing the small molecule phenamil as a novel biofactor for bone regenerative engineering, J. Tissue Eng. Regen. Med., 8, 728, 10.1002/term.1573 Lo, 2012, The small molecule PKA-specific cyclic AMP analogue as an inducer of osteoblast-like cells differentiation and mineralization, J. Tissue Eng. Regen. Med., 6, 40, 10.1002/term.395 Lo, 2011, Current patents on osteoinductive molecules for bone tissue engineering, Recent Patents Biomed. Eng., 4, 153, 10.2174/1874764711104030153 Lo, 2011, Activation of cyclic amp/protein kinase: a signaling pathway enhances osteoblast cell adhesion on biomaterials for regenerative engineering, J. Orthop. Res., 29, 602, 10.1002/jor.21276 Laurencin, 2014, Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications, Drug Discov. Today, 19, 794, 10.1016/j.drudis.2014.01.012 Lo, 2012, The role of small molecules in musculoskeletal regeneration, Regen. Med., 7, 535, 10.2217/rme.12.33 Ge, 2006, Biomaterials and scaffolds for ligament tissue engineering, J. Biomed. Mater. Res. A, 77A, 639, 10.1002/jbm.a.30578 Petrigliano, 2006, Tissue engineering for anterior cruciate ligament reconstruction: a review of current strategies, Arthroscopy, 22, 441, 10.1016/j.arthro.2006.01.017 Levine, 2013, Clinically relevant injury patterns after an anterior cruciate ligament injury provide insight into injury mechanisms, Am. J. Sports Med., 41, 385, 10.1177/0363546512465167 Quatman, 2011, Cartilage pressure distributions provide a footprint to define female anterior cruciate ligament injury mechanisms, Am. J. Sports Med., 39, 1706, 10.1177/0363546511400980 Fu, 2000, Current trends in anterior cruciate ligament reconstruction: part II. Operative procedures and clinical correlations, Am. J. Sports Med., 28, 124, 10.1177/03635465000280010801 Kwansa, 2010, Novel matrix based anterior cruciate ligament (ACL) regeneration, Soft Matter, 6, 5016, 10.1039/c0sm00182a Lewis, 2014 Dunn, 1993, Optimization of extruded collagen fibers for ACL reconstruction, J. Biomed. Mater. Res., 27, 1545, 10.1002/jbm.820271211 Bellincampi, 1998, Viability of fibroblast-seeded ligament analogs after autogenous implantation, J. Orthop. Res., 16, 414, 10.1002/jor.1100160404 Majima, 2005, Alginate and chitosan polyion complex hybrid fibers for scaffolds in ligament and tendon tissue engineering, J. Orthop. Sci., 10, 302, 10.1007/s00776-005-0891-y Hansson, 2012, In vitro evaluation of an RGD-functionalized chitosan derivative for enhanced cell adhesion, Carbohydr. Polym., 90, 1494, 10.1016/j.carbpol.2012.07.020 Bourke, 2004, Preliminary development of a novel resorbable synthetic polymer fiber scaffold for anterior cruciate ligament reconstruction, Tissue Eng., 10, 43, 10.1089/107632704322791682 Dürselen, 2001, Resorbable polymer fibers for ligament augmentation, J. Biomed. Mater. Res., 58, 666, 10.1002/jbm.1067 Cooper, 2005, Fiber-based tissue-engineered scaffold for ligament replacement: design considerations and in vitro evaluation, Biomaterials, 26, 1523, 10.1016/j.biomaterials.2004.05.014 Laurencin, 2014, Mechanically competent scaffold for ligament and tendon regeneration, US Patent, 8758437, B2 Laurencin, 2005, Ligament tissue engineering: an evolutionary materials science approach, Biomaterials, 26, 7530, 10.1016/j.biomaterials.2005.05.073 Sarukawa, 2011, Effects of chitosan-coated fibers as a scaffold for three-dimensional cultures of rabbit fibroblasts for ligament tissue engineering, J. Biomater. Sci. Polym. Ed., 22, 717, 10.1163/092050610X491067 Cooper, 2006, Evaluation of the anterior cruciate ligament, medial collateral ligament, Achilles tendon and patellar tendon as cell sources for tissue-engineered ligament, Biomaterials, 27, 2747, 10.1016/j.biomaterials.2005.12.013 Cooper, 2007, Biomimetic tissue-engineered anterior cruciate ligament replacement, Proc. Natl. Acad. Sci., 104, 3049, 10.1073/pnas.0608837104 Ouyang, 2003, Knitted poly-lactide-co-glycolide scaffold loaded with bone marrow stromal cells in repair and regeneration of rabbit Achilles tendon, Tissue Eng., 9, 431, 10.1089/107632703322066615 Karamuk, 2004, Tissue engineered composite of a woven fabric scaffold with tendon cells, response on mechanical simulation in vitro, Compos. Sci. Technol., 64, 885, 10.1016/j.compscitech.2003.09.004 Li, 2006, Fabrication and characterization of six electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for tissue engineering applications, Acta Biomater., 2, 377, 10.1016/j.actbio.2006.02.005 Subramony, 2013, The guidance of stem cell differentiation by substrate alignment and mechanical stimulation, Biomaterials, 34, 1942, 10.1016/j.biomaterials.2012.11.012 Sahoo, 2010, PLGA nanofiber-coated silk microfibrous scaffold for connective tissue engineering, J. Biomed. Mater. Res. B Appl. Biomater., 95B, 19, 10.1002/jbm.b.31678 Kim, 2012, Composite system of PLCL scaffold and heparin-based hydrogel for regeneration of partial-thickness cartilage defects, Biomacromolecules, 13, 2287, 10.1021/bm3005353 Barber, 2013, Braided nanofibrous scaffold for tendon and ligament tissue engineering, Tissue Eng. A, 19, 1265, 10.1089/ten.tea.2010.0538 Lu, 2005, Anterior cruciate ligament regeneration using braided biodegradable scaffolds: in vitro optimization studies, Biomaterials, 26, 4805, 10.1016/j.biomaterials.2004.11.050 Kimura, 2008, Regeneration of anterior cruciate ligament by biodegradable scaffold combined with local controlled release of basic fibroblast growth factor and collagen wrapping, Tissue Eng. Part C Methods, 14, 47, 10.1089/tec.2007.0286 Qu, 2015, Engineering complex orthopaedic tissues via strategic biomimicry, Ann. Biomed. Eng., 43, 697, 10.1007/s10439-014-1190-6 Lu, 2010, Tissue engineering strategies for the regeneration of orthopedic interfaces, Ann. Biomed. Eng., 38, 2142, 10.1007/s10439-010-0046-y Freeman, 2007, Tissue engineering of the anterior cruciate ligament using a braid-twist scaffold design, J. Biomech., 40, 2029, 10.1016/j.jbiomech.2006.09.025 Mosher, 2015, Stratified scaffold design for engineering composite tissues, Methods (San Diego, Calif), 84, 99, 10.1016/j.ymeth.2015.03.029 Spalazzi, 2013, Quantitative mapping of matrix content and distribution across the ligament-to-bone insertion, PLoS One, 8, 10.1371/journal.pone.0074349 Lynn, 2010, Design of a multiphase osteochondral scaffold. I. Control of chemical composition, J. Biomed. Mater. Res. A, 92A, 1057 Harley, 2010, Design of a multiphase osteochondral scaffold III: fabrication of layered scaffolds with continuous interfaces, J. Biomed. Mater. Res. A, 92A, 1078 Ellis, 1996, Recent advances in tissue synthesis in vivo by use of collagen-glycosaminoglycan copolymers, Biomaterials, 17, 291, 10.1016/0142-9612(96)85567-0 Ivanovski, 2014, Multiphasic scaffolds for periodontal tissue engineering, J. Dent. Res., 93, 1212, 10.1177/0022034514544301 Karring, 1993, Development of the biological concept of guided tissue regeneration—animal and human studies, Periodontol., 1, 26, 10.1111/j.1600-0757.1993.tb00204.x Carlo Reis, 2011, Periodontal regeneration using a bilayered PLGA/calcium phosphate construct, Biomaterials, 32, 9244, 10.1016/j.biomaterials.2011.08.040 Spalazzi, 2006, Development of controlled matrix heterogeneity on a triphasic scaffold for orthopedic interface tissue engineering, Tissue Eng., 12, 3497, 10.1089/ten.2006.12.3497 Jiang, 2005, Co-culture of osteoblasts and chondrocytes modulates cellular differentiation in vitro, Biochem. Biophys. Res. Commun., 338, 762, 10.1016/j.bbrc.2005.10.025 Spalazzi, 2008, In vivo evaluation of a multiphased scaffold designed for orthopaedic interface tissue engineering and soft tissue-to-bone integration, J. Biomed. Mater. Res. A, 86A, 1, 10.1002/jbm.a.32073 He, 2015, Design and fabrication of biomimetic multiphased scaffolds for ligament-to-bone fixation, Mater. Sci. Eng. C, 50, 12, 10.1016/j.msec.2015.01.088 Chung, 2014, A biodegradable tri-component graft for anterior cruciate ligament reconstruction, J. Tissue Eng. Regen. Med. He, 2014, Electrospinning of nanofibrous scaffolds with continuous structure and material gradients, Mater. Lett., 137, 393, 10.1016/j.matlet.2014.09.045 Singh, 2008, Microsphere-based seamless scaffolds containing macroscopic gradients of encapsulated factors for tissue engineering, Tissue Eng. Part C Methods, 14, 299, 10.1089/ten.tec.2008.0167 Dormer, 2013, Effect of different sintering methods on bioactivity and release of proteins from PLGA microspheres, Mater. Sci. Eng. C, 33, 4343, 10.1016/j.msec.2013.06.026 Bhamidipati, 2013, Subcritical CO2 sintering of microspheres of different polymeric materials to fabricate scaffolds for tissue engineering, Mater. Sci. Eng. C, 33, 4892, 10.1016/j.msec.2013.08.010 Mohan, 2014, The potential of encapsulating “raw materials” in 3D osteochondral gradient scaffolds, Biotechnol. Bioeng., 111, 829, 10.1002/bit.25145 Mohan, 2015, Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep, Regen. Med., 10, 709, 10.2217/rme.15.38 Phillips, 2008, Engineering graded tissue interfaces, Proc. Natl. Acad. Sci., 105, 12170, 10.1073/pnas.0801988105 Veth, 1986, Experimental meniscal lesions reconstructed with a carbon fiber-polyurethane-poly(l-lactide) graft, Clin. Orthop. Relat. Res., 286-93 Ike, 1991, Experimental studies on an artificial trachea of collagen-coated poly(l-lactic acid) mesh or unwoven cloth combined with a periosteal graft, ASAIO Trans./Am. Soc. Artif. Intern. Organs, 37, 24, 10.1097/00002480-199101000-00008 von Schroeder, 1991, The use of polylactic acid matrix and periosteal grafts for the reconstruction of rabbit knee articular defects, J. Biomed. Mater. Res., 25, 329, 10.1002/jbm.820250305 Zhang, 2012, The impact of PLGA scaffold orientation on in vitro cartilage regeneration, Biomaterials, 33, 2926, 10.1016/j.biomaterials.2012.01.006 Yang, 2012, Improved mesenchymal stem cells attachment and in vitro cartilage tissue formation on chitosan-modified poly(l-lactide-co-epsilon-caprolactone) scaffold, Tissue Eng. A, 18, 242, 10.1089/ten.tea.2011.0315 Li, 2012, A viscoelastic chitosan-modified three-dimensional porous poly (l-lactide-co-ε-caprolactone) scaffold for cartilage tissue engineering, J. Biomater. Sci. Polym. Ed., 23, 405, 10.1163/092050610X551970 Chao, 2013, Poly (l-lactide-co-caprolactone) scaffolds enhanced with poly (β-hydroxybutyrate-co-β-hydroxyvalerate) microspheres for cartilage regeneration, Biomed. Mater., 8, 025005, 10.1088/1748-6041/8/2/025005 Stenhamre, 2013, Nanosized fibers' effect on adult human articular chondrocytes behavior, Mater. Sci. Eng. C, 33, 1539, 10.1016/j.msec.2012.12.059 Rosenzweig, 2015, 3D-printed ABS and PLA scaffolds for cartilage and nucleus pulposus tissue regeneration, Int. J. Mol. Sci., 16, 15118, 10.3390/ijms160715118 Pacifici, 2014, Introduction to the mini-review series “articular cartilage: biology, pathology and repair”, Matrix Biol., 39, 1, 10.1016/j.matbio.2014.08.004 Sophia Fox, 2009, The basic science of articular cartilage: structure, composition, and function, Sports Health, 1, 461, 10.1177/1941738109350438 Buckwalter, 2005, Articular cartilage and osteoarthritis, Instr. Course Lect., 54, 465 Li, 2006, Demineralized bone matrix gelatin as scaffold for osteochondral tissue engineering, Biomaterials, 27, 2426, 10.1016/j.biomaterials.2005.11.040 Tyler, 2012, Rehabilitation following osteochondral injury to the knee, Curr. Rev. Musculoskelet. Med., 5, 72, 10.1007/s12178-011-9108-5 Oussedik, 2015, Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation: a systematic review, Arthroscopy, 31, 732, 10.1016/j.arthro.2014.11.023 Blackman, 2013, Correlation between magnetic resonance imaging and clinical outcomes after cartilage repair surgery in the knee: a systematic review and meta-analysis, Am. J. Sports Med., 41, 1426, 10.1177/0363546513485931 Miller, 2009, MR imaging of the knee, Sports Med. Arthrosc. Rev., 17, 56, 10.1097/JSA.0b013e3181974353 Filardo, 2013, Scaffold-based repair for cartilage healing: a systematic review and technical note, Arthroscopy, 29, 174, 10.1016/j.arthro.2012.05.891 Ossendorf, 2007, Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: 2-year clinical results, Arthritis Res. Ther., 9, R41, 10.1186/ar2180 Kreuz, 2009, Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results, Arthritis Res. Ther., 11, 10.1186/ar2638 Kreuz, 2011, Repair of focal cartilage defects with scaffold-assisted autologous chondrocyte grafts: clinical and biomechanical results 48months after transplantation, Am. J. Sports Med., 39, 1697, 10.1177/0363546511403279 Kon, 2014, Clinical results of multilayered biomaterials for osteochondral regeneration, J. Exp. Orthop., 1, 10, 10.1186/s40634-014-0010-0 Bekkers, 2013, Articular cartilage evaluation after TruFit plug implantation analyzed by delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), Am. J. Sports Med., 41, 1290, 10.1177/0363546513483536 Dhollander, 2012, A pilot study of the use of an osteochondral scaffold plug for cartilage repair in the knee and how to deal with early clinical failures., Arthroscopy, 28, 225, 10.1016/j.arthro.2011.07.017 Verhaegen, 2014, TruFit plug for repair of osteochondral defects—where is the evidence? Systematic review of literature, Cartilage Jeon, 2014, Perspectives in multiphasic osteochondral tissue engineering, Anat. Rec., 297, 26, 10.1002/ar.22795 Cui, 2011, Repair of articular cartilage defects with tissue-engineered osteochondral composites in pigs, J. Biosci. Bioeng., 111, 493, 10.1016/j.jbiosc.2010.11.023 Yu, 2012, Improvement of intertrochanteric bone quality in osteoporotic female rats after injection of polylactic acid-polyglycolic acid copolymer/collagen type I microspheres combined with bone mesenchymal stem cells, Int. Orthop., 36, 2163, 10.1007/s00264-012-1543-4 Chang, 2012, The combined effects of continuous passive motion treatment and acellular PLGA implants on osteochondral regeneration in the rabbit, Biomaterials, 33, 3153, 10.1016/j.biomaterials.2011.12.054 Cui, 2013, Poly(ᴅ-lactide)/poly(caprolactone) nanofiber-thermogelling chitosan gel composite scaffolds for osteochondral tissue regeneration in a rat model, J. Bioact. Compat. Polym., 10.1177/0883911512472278 Ding, 2013, Regeneration of a goat femoral head using a tissue-specific, biphasic scaffold fabricated with CAD/CAM technology, Biomaterials, 34, 6706, 10.1016/j.biomaterials.2013.05.038 Qi, 2014, Cartilage repair using mesenchymal stem cell (MSC) sheet and MSCs-loaded bilayer PLGA scaffold in a rabbit model, Knee Surg., Sports Traumatol. Arthrosc., 22, 1424, 10.1007/s00167-012-2256-3 Gong, 2014, Proteomic analysis profile of engineered articular cartilage with chondrogenic differentiated adipose tissue-derived stem cells loaded polyglycolic acid mesh for weight-bearing area defect repair, Tissue Eng. A, 20, 575 Caminal, 2015, Cartilage resurfacing potential of PLGA scaffolds loaded with autologous cells from cartilage, fat, and bone marrow in an ovine model of osteochondral focal defect, Cytotechnology Chen, 2006, Preparation of a biphasic scaffold for osteochondral tissue engineering, Mater. Sci. Eng. C, 26, 118, 10.1016/j.msec.2005.07.024 Keeney, 2009, The osteochondral junction and its repair via bi-phasic tissue engineering scaffolds, Tissue Eng. Part B Rev., 15, 55, 10.1089/ten.teb.2008.0388 Yousefi, 2015, Current strategies in multiphasic scaffold design for osteochondral tissue engineering: a review, J. Biomed. Mater. Res. A, 103, 2460, 10.1002/jbm.a.35356 Swieszkowski, 2007, Repair and regeneration of osteochondral defects in the articular joints, Biomed. Eng., 24, 489 Schaefer, 2000, In vitro generation of osteochondral composites, Biomaterials, 21, 2599, 10.1016/S0142-9612(00)00127-7 Duan, 2014, The effects of pore size in bilayered poly(lactide-co-glycolide) scaffolds on restoring osteochondral defects in rabbits, J. Biomed. Mater. Res. A, 102, 180, 10.1002/jbm.a.34683 Yan, 2015, Current concepts and challenges in osteochondral tissue engineering and regenerative medicine, ACS Biomat. Sci. Eng., 1, 183, 10.1021/ab500038y Da, 2013, The impact of compact layer in biphasic scaffold on osteochondral tissue engineering, PLoS One, 8, 10.1371/journal.pone.0054838 Atesok, 2014, Multilayer scaffolds in orthopaedic tissue engineering, Knee Surg. Sports Traumatol. Arthrosc., 1-9 Nukavarapu SP, Laurencin CT, Amini AR, Dorcemus DL. Gradient Porous Scaffolds. US Patent US20140178455; 2013. Park, 2008, Development of dual scale scaffolds via direct polymer melt deposition and electrospinning for applications in tissue regeneration, Acta Biomater., 4, 1198, 10.1016/j.actbio.2008.03.019 Tang, 2012, Preparation of PLGA scaffolds with graded pores by using a gelatin-microsphere template as porogen, J. Biomater. Sci. Polym. Ed., 23, 2241, 10.1163/156856211X614185 Sun, 2009, The regenerative effect of platelet-rich plasma on healing in large osteochondral defects, Int. Orthop. (SICOT), 34, 589, 10.1007/s00264-009-0793-2 Mohan, 2011, Continuous gradients of material composition and growth factors for effective regeneration of the osteochondral interface, Tissue Eng. A, 17, 2845, 10.1089/ten.tea.2011.0135 Yeo, 2014, Cell-printed hierarchical scaffolds consisting of micro-sized polycaprolactone (PCL) and electrospun PCL nanofibers/cell-laden alginate struts for tissue regeneration, J. Mater. Chem. B, 2, 314, 10.1039/C3TB21163K Jeon, 2014, Multiphasic construct studied in an ectopic osteochondral defect model, J. R. Soc. Interface, 11, 10.1098/rsif.2014.0184 Jin-Hyung, 2012, Bioprinting of a mechanically enhanced three-dimensional dual cell-laden construct for osteochondral tissue engineering using a multi-head tissue/organ building system, J. Micromech. Microeng., 22, 085014, 10.1088/0960-1317/22/8/085014 Melchels, 2010, Mathematically defined tissue engineering scaffold architectures prepared by stereolithography, Biomaterials, 31, 6909, 10.1016/j.biomaterials.2010.05.068 Fox, 2012, The basic science of human knee menisci: structure, composition, and function, Sports Health, 4, 340, 10.1177/1941738111429419 Verdonk, 2005, Characterisation of human knee meniscus cell phenotype, Osteoarthr. Cartil., 13, 548, 10.1016/j.joca.2005.01.010 Bach, 2005, Arthroscopic meniscal repair, J. Knee Surg., 18, 278, 10.1055/s-0030-1248192 Fairbank, 1948, Knee joint changes after meniscectomy, J. Bone Joint Surg. Br. Vol., 30, 664, 10.1302/0301-620X.30B4.664 Rangger, 1997, Partial meniscectomy and osteoarthritis, Sports Med., 23, 61, 10.2165/00007256-199723010-00006 van Tienen, 2009, Meniscus replacement using synthetic materials, Clin. Sports Med., 28, 143, 10.1016/j.csm.2008.08.003 Lee, 2014, Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep, Sci. Transl. Med., 6, 266ra171, 10.1126/scitranslmed.3009696 Esposito, 2013, PLDLA/PCL-T scaffold for meniscus tissue engineering, BioRes. Open Access, 2, 138, 10.1089/biores.2012.0293 Baek, 2015, Meniscus tissue engineering using a novel combination of electrospun scaffolds and human meniscus cells embedded within an extracellular matrix hydrogel, J. Orthop. Res., 33, 572, 10.1002/jor.22802 Vaquette, 2013, A simple method for fabricating 3-D multilayered composite scaffolds, Acta Biomater., 9, 4599, 10.1016/j.actbio.2012.08.015