Engineered three-dimensional scaffolds for enhanced bone regeneration in osteonecrosis

Osteonecrosis, which is typically induced by trauma, glucocorticoid abuse, or alcoholism, is one of the most severe diseases in clinical orthopedics. Osteonecrosis often leads to joint destruction, and arthroplasty is eventually required. Enhancement of bone regeneration is a critical management strategy employed in osteonecrosis therapy. Bone tissue engineering based on engineered three-dimensional (3D) scaffolds with appropriate architecture and osteoconductive activity, alone or functionalized with bioactive factors, have been developed to enhance bone regeneration in osteonecrosis. In this review, we elaborate on the ideal properties of 3D scaffolds for enhanced bone regeneration in osteonecrosis, including biocompatibility, degradability, porosity, and mechanical performance. In addition, we summarize the development of 3D scaffolds alone or functionalized with bioactive factors for accelerating bone regeneration in osteonecrosis and discuss their prospects for translation to clinical practice.

[1]  Jiang Peng,et al.  Phytomolecule icaritin incorporated PLGA/TCP scaffold for steroid-associated osteonecrosis: Proof-of-concept for prevention of hip joint collapse in bipedal emus and mechanistic study in quadrupedal rabbits , 2015, Biomaterials.

[2]  K. Schmiegelow,et al.  Hyperlipidemia is a risk factor for osteonecrosis in children and young adults with acute lymphoblastic leukemia , 2017, Haematologica.

[3]  A Hatefi,et al.  Biodegradable injectable in situ forming drug delivery systems. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[4]  Yixiang Wang,et al.  Icaritin, an Exogenous Phytomolecule, Enhances Osteogenesis but Not Angiogenesis—An In Vitro Efficacy Study , 2012, PloS one.

[5]  J. Griffith,et al.  Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone , 2006, Bone.

[6]  Jiacan Su,et al.  Promotion of in vivo degradability, vascularization and osteogenesis of calcium sulfate-based bone cements containing nanoporous lithium doping magnesium silicate , 2017, International journal of nanomedicine.

[7]  Lobat Tayebi,et al.  Porous magnesium-based scaffolds for tissue engineering. , 2017, Materials science & engineering. C, Materials for biological applications.

[8]  Maryam Tabrizian,et al.  Preclinical safety study of a combined therapeutic bone wound dressing for osteoarticular regeneration , 2019, Nature Communications.

[9]  Xiaowei Yu,et al.  A high-fat diet aggravates osteonecrosis through a macrophage-derived IL-6 pathway , 2019, International immunology.

[10]  J. Jones,et al.  The pathophysiologic role of fat in dysbaric osteonecrosis. , 1993, Clinical orthopaedics and related research.

[11]  D. Puleo,et al.  Hydroxyapatite-reinforced in situ forming PLGA systems for intraosseous injection. , 2015, Journal of biomedical materials research. Part A.

[12]  Xiyang Zhang,et al.  MMP-3 and MMP-8 single-nucleotide polymorphisms are related to alcohol-induced osteonecrosis of the femoral head in Chinese males , 2017, Oncotarget.

[13]  David F. Williams.  On the mechanisms of biocompatibility. , 2008, Biomaterials.

[14]  P. Revell,et al.  The extent of osteocyte death in the proximal femur of patients with osteonecrosis of the femoral head. , 2001, The Journal of bone and joint surgery. British volume.

[15]  Lei Wang,et al.  Adenovirus-Mediated Expression of BMP-2 and BFGF in Bone Marrow Mesenchymal Stem Cells Combined with Demineralized Bone Matrix For Repair of Femoral Head Osteonecrosis in Beagle Dogs , 2017, Cellular Physiology and Biochemistry.

[16]  Li Li,et al.  In vitro study on the degradation of lithium-doped hydroxyapatite for bone tissue engineering scaffold. , 2016, Materials science & engineering. C, Materials for biological applications.

[17]  Wei Zhu,et al.  Self-healing and injectable hybrid hydrogel for bone regeneration of femoral head necrosis and defect. , 2019, Biochemical and biophysical research communications.

[18]  Renchong Wang,et al.  Acceleration of bone regeneration by activating Wnt/β-catenin signalling pathway via lithium released from lithium chloride/calcium phosphate cement in osteoporosis , 2017, Scientific Reports.

[19]  Brendon M. Baker,et al.  Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues , 2012, Journal of Cell Science.

[20]  K. Pienta,et al.  Erythropoietin Couples Hematopoiesis with Bone Formation , 2010, PloS one.

[21]  A. Parfitt,et al.  Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. , 1998, The Journal of clinical investigation.

[22]  I. Hermodsson.  On the problem of trauma and aseptic osteonecrosis. , 1947, Acta radiologica.

[23]  M. Ho,et al.  Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair , 2013, International journal of nanomedicine.

[24]  Dai Fukumura,et al.  Tissue engineering: Creation of long-lasting blood vessels , 2004, Nature.

[25]  Zhihong Wu,et al.  3D-printed porous titanium changed femoral head repair growth patterns: osteogenesis and vascularisation in porous titanium , 2017, Journal of Materials Science: Materials in Medicine.

[26]  Di-sheng Yang,et al.  Effects of a bone graft substitute consisting of porous gradient HA/ZrO2 and gelatin/chitosan slow‐release hydrogel containing BMP‐2 and BMSCs on lumbar vertebral defect repair in rhesus monkey , 2018, Journal of tissue engineering and regenerative medicine.

[27]  Jian-hua Wu,et al.  Role of FGF-2 Transfected Bone Marrow Mesenchymal Stem Cells in Engineered Bone Tissue for Repair of Avascular Necrosis of Femoral Head in Rabbits , 2018, Cellular Physiology and Biochemistry.

[28]  I. Martin,et al.  Engineered, axially-vascularized osteogenic grafts from human adipose-derived cells to treat avascular necrosis of bone in a rat model. , 2017, Acta biomaterialia.

[29]  W. Ni,et al.  Fludarabine inhibits STAT1-mediated up-regulation of caspase-3 expression in dexamethasone-induced osteoblasts apoptosis and slows the progression of steroid-induced avascular necrosis of the femoral head in rats , 2017, Apoptosis.

[30]  A. Lamberti,et al.  Graphene Oxide Finely Tunes the Bioactivity and Drug Delivery of Mesoporous ZnO Scaffolds. , 2018, ACS applied materials & interfaces.

[31]  Kunzheng Wang,et al.  Core decompression in combination with nano-hydroxyapatite/polyamide 66 rod for the treatment of osteonecrosis of the femoral head , 2013, Archives of Orthopaedic and Trauma Surgery.

[32]  Xiu-zhen Zhang,et al.  Icariin induces osteoblast proliferation, differentiation and mineralization through estrogen receptor-mediated ERK and JNK signal activation. , 2013, European journal of pharmacology.

[33]  J. Song,et al.  A BMSCs-laden Quercetin/Duck's Feet Collagen/Hydroxyapatite Sponge for Enhanced Bone Regeneration. , 2019, Journal of biomedical materials research. Part A.

[34]  C. Laurencin,et al.  The role of small molecules in musculoskeletal regeneration. , 2012, Regenerative medicine.

[35]  R. Pascarella,et al.  Traumatic hip fracture-dislocation: A middle-term follow up study and a proposal of new classification system of hip joint associated injury. , 2019, Injury.

[36]  Gang Li,et al.  Repair of osteonecrosis of the femoral head , 2019, Der Orthopäde.

[37]  J. M. Garcı́a,et al.  Modelling bone tissue fracture and healing: a review ☆ , 2004 .

[38]  C. Rey,et al.  Mechanisms of Action and Therapeutic Potential of Strontium in Bone , 2001, Calcified Tissue International.

[39]  Zhongmin Jin,et al.  Design and fabrication of a novel porous implant with pre-set channels based on ceramic stereolithography for vascular implantation , 2011, Biofabrication.

[40]  B. Lévy,et al.  Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells: Physiological and Therapeutic Perspectives , 2004, Circulation.

[41]  Yuen-Kit Cheng,et al.  Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides , 2007, Chinese medicine.

[42]  Chu Cheng,et al.  Toxicity of selenium nanoparticles in male Sprague-Dawley rats at supranutritional and nonlethal levels. , 2014, Life sciences.

[43]  Chunli Song,et al.  Simvastatin induces osteoblastic differentiation and inhibits adipocytic differentiation in mouse bone marrow stromal cells. , 2003, Biochemical and biophysical research communications.

[44]  M. Menger,et al.  Temporal and spatial vascularization patterns of unions and nonunions: role of vascular endothelial growth factor and bone morphogenetic proteins. , 2012, The Journal of bone and joint surgery. American volume.

[45]  Benjamin M. Wu,et al.  Microporous methacrylated glycol chitosan-montmorillonite nanocomposite hydrogel for bone tissue engineering , 2019, Nature Communications.

[46]  J. Kang,et al.  Clinical efficiency of bone marrow mesenchymal stem cell implantation for osteonecrosis of the femoral head: a matched pair control study with simple core decompression , 2018, Stem Cell Research & Therapy.

[47]  Benjamin B. Rothrauff,et al.  Robust bone regeneration through endochondral ossification of human mesenchymal stem cells within their own extracellular matrix. , 2019, Biomaterials.

[48]  A. Bolstad,et al.  Cross-linked gelatin-nanocellulose scaffolds for bone tissue engineering , 2020 .

[49]  Peter X Ma,et al.  The release profiles and bioactivity of parathyroid hormone from poly(lactic-co-glycolic acid) microspheres. , 2004, Biomaterials.

[50]  Changshun Ruan,et al.  Three-Dimensional Printing of Biodegradable Piperazine-Based Polyurethane-Urea Scaffolds with Enhanced Osteogenesis for Bone Regeneration. , 2019, ACS applied materials & interfaces.

[51]  V. Pinskerova,et al.  Strengths and Limitations , 2022 .

[52]  Zhenzhong Zhu,et al.  Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway , 2017, Theranostics.

[53]  Tiantong Sun,et al.  BMSC affinity peptide-functionalized β-tricalcium phosphate scaffolds promoting repair of osteonecrosis of the femoral head , 2019, Journal of Orthopaedic Surgery and Research.

[54]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.

[55]  Di Chen,et al.  Combination Treatment of Biomechanical Support and Targeted Intra‐arterial Infusion of Peripheral Blood Stem Cells Mobilized by Granulocyte‐Colony Stimulating Factor for the Osteonecrosis of the Femoral Head: A Randomized Controlled Clinical Trial , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[56]  B. Jiang,et al.  The use of anticoagulants for prevention and treatment of osteonecrosis of the femoral head , 2017, Medicine.

[57]  A. Kaneuji,et al.  Osteonecrosis development in a novel rat model characterized by a single application of oxidative stress. , 2011, Arthritis and rheumatism.

[58]  Junqing Hu,et al.  Treatment of steroid-induced osteonecrosis of the femoral head using porous Se@SiO2 nanocomposites to suppress reactive oxygen species , 2017, Scientific Reports.

[59]  Y. Ikada,et al.  Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells. , 2005, Biomaterials.

[60]  David S Hungerford,et al.  Nontraumatic osteonecrosis of the femoral head: ten years later. , 2006, The Journal of bone and joint surgery. American volume.

[61]  Xijian Liu,et al.  Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis , 2018, International journal of nanomedicine.

[62]  M. Delcogliano,et al.  Treatment of Large Knee Osteochondral Lesions With a Biomimetic Scaffold , 2014, The American journal of sports medicine.

[63]  Kunzheng Wang,et al.  The effect of deferoxamine on angiogenesis and bone repair in steroid-induced osteonecrosis of rabbit femoral heads , 2015, Experimental biology and medicine.

[64]  Joshua J Jacobs,et al.  Experimental and clinical performance of porous tantalum in orthopedic surgery. , 2006, Biomaterials.

[65]  Wei Xu,et al.  Topological design and additive manufacturing of porous metals for bone scaffolds and orthopaedic implants: A review. , 2016, Biomaterials.

[66]  Yun-yu Hu,et al.  Application of BCBB/BMP/bFGF Complex in Repairing Femoral Head Necrosis in Rabbit Models , 2015 .

[67]  Zi-rong Li,et al.  Heterotopic ossification related to the use of recombinant human BMP-2 in osteonecrosis of femoral head , 2017, Medicine.

[68]  Yao-sheng Liu,et al.  Core decompression and implantation of bone marrow mononuclear cells with porous hydroxylapatite composite filler for the treatment of osteonecrosis of the femoral head , 2012, Archives of Orthopaedic and Trauma Surgery.

[69]  Xiaofeng Chen,et al.  Promoting in vivo early angiogenesis with sub-micrometer strontium-contained bioactive microspheres through modulating macrophage phenotypes. , 2018, Biomaterials.

[70]  G. Muschler,et al.  Evidence for the Use of Cell-Based Therapy for the Treatment of Osteonecrosis of the Femoral Head: A Systematic Review of the Literature. , 2017, The Journal of arthroplasty.

[71]  Z. Zhong,et al.  Bone mesenchymal stem cells co-expressing VEGF and BMP-6 genes to combat avascular necrosis of the femoral head , 2017, Experimental and therapeutic medicine.

[72]  T. Maekawa,et al.  POLYMERIC SCAFFOLDS IN TISSUE ENGINEERING APPLICATION: A REVIEW , 2011 .

[73]  K. Neoh,et al.  Electrical stimulation of adipose‐derived mesenchymal stem cells and endothelial cells co‐cultured in a conductive scaffold for potential orthopaedic applications , 2018, Journal of tissue engineering and regenerative medicine.

[74]  Matthew C. Phipps,et al.  Intraosseous Delivery of Bone Morphogenic Protein-2 Using a Self-Assembling Peptide Hydrogel. , 2016, Biomacromolecules.

[75]  T. Uemura,et al.  Bone regeneration induced by adenoviral vectors carrying til‐1/Cbfa1 genes implanted with biodegradable porous materials in animal models of osteonecrosis of the femoral head , 2008, Journal of tissue engineering and regenerative medicine.

[76]  N. Ferrara,et al.  The biology of VEGF and its receptors , 2003, Nature Medicine.

[77]  D. Bluemke,et al.  Atraumatic Osteonecrosis of the Knee* , 2000, The Journal of bone and joint surgery. American volume.

[78]  M. Scherer,et al.  Expression of Bone Morphogenic Proteins and Receptors at the Injured Growth Plate Cartilage in Young Rats , 2006, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[79]  M. Rouabhia,et al.  Effect of BMP-2 and BMP-7 homodimers and a mixture of BMP-2/BMP-7 homodimers on osteoblast adhesion and growth following culture on a collagen scaffold , 2008, Biomedical materials.

[80]  Ivan Martin,et al.  Three‐Dimensional Perfusion Culture of Human Adipose Tissue‐Derived Endothelial and Osteoblastic Progenitors Generates Osteogenic Constructs with Intrinsic Vascularization Capacity , 2007, Stem cells.

[81]  G. Yin,et al.  Effects of combinations of BMP-2 with FGF-2 and/or VEGF on HUVECs angiogenesis in vitro and CAM angiogenesis in vivo , 2014, Cell and Tissue Research.

[82]  Q. Guo,et al.  Micro-CT-based bone ceramic scaffolding and its performance after seeding with mesenchymal stem cells for repair of load-bearing bone defect in canine femoral head. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[83]  Xin Wang,et al.  3D printing of polymer matrix composites: A review and prospective , 2017 .

[84]  Pinar Zorlutuna,et al.  Enabling personalized implant and controllable biosystem development through 3D printing. , 2018, Biotechnology advances.

[85]  H. Jung,et al.  Fabrication of in vitro 3D mineralized tissue by fusion of composite spheroids incorporating biomineral-coated nanofibers and human adipose-derived stem cells. , 2018, Acta biomaterialia.

[86]  P. Hernigou,et al.  Decrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid-induced osteonecrosis. , 1999, The Journal of bone and joint surgery. British volume.

[87]  S. Hung,et al.  Benefits of hypoxic culture on bone marrow multipotent stromal cells. , 2012, American journal of blood research.

[88]  M. Mozafari,et al.  Bioactive Glasses: Sprouting Angiogenesis in Tissue Engineering. , 2018, Trends in biotechnology.

[89]  Y. Shoenfeld,et al.  Pathogenesis and natural history of osteonecrosis. , 2002, Seminars in arthritis and rheumatism.

[90]  F. Saltel,et al.  Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. , 2008, Bone.

[91]  P. Ohtonen,et al.  Young patients with hematologic and lymphatic malignancies have an increased risk of hip and knee arthroplasty , 2016, Acta oncologica.

[92]  M. Salarian,et al.  Angiogenic Rg1 /Sr-Doped TiO2 Nanowire/Poly(Propylene Fumarate) Bone Cement Composites. , 2017, Macromolecular bioscience.

[93]  T. Pufe,et al.  Enoxaparin Prevents Steroid-Related Avascular Necrosis of the Femoral Head , 2014, TheScientificWorldJournal.

[94]  Dae Hoon Lee,et al.  Quercetin Inlaid Silk Fibroin/Hydroxyapatite Scaffold Promotes Enhanced Osteogenesis. , 2018, ACS applied materials & interfaces.

[95]  X. Weng,et al.  Bone-strengthening pill (BSP) promotes bone cell and chondrocyte repair, and the clinical and experimental study of BSP in the treatment of osteonecrosis of the femoral head , 2017, Oncotarget.

[96]  Guanglong Li,et al.  3D Printing of Lotus Root‐Like Biomimetic Materials for Cell Delivery and Tissue Regeneration , 2017, Advanced science.

[97]  Jinhai Zhao,et al.  Porous lithium-doped hydroxyapatite scaffold seeded with hypoxia-preconditioned bone-marrow mesenchymal stem cells for bone-tissue regeneration , 2018, Biomedical materials.

[98]  D. Illingworth,et al.  Rhabdomyolysis after taking atorvastatin with gemfibrozil. , 1998, The American journal of cardiology.

[99]  Rozalia Dimitriou,et al.  Bone regeneration: current concepts and future directions , 2011, BMC medicine.

[100]  C. Rubin,et al.  Biology of bone and how it orchestrates the form and function of the skeleton , 2001, European Spine Journal.

[101]  Kunzheng Wang,et al.  Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and osteogenesis in rabbit femoral head osteonecrosis. , 2015, Bone.

[102]  Xiuzhi Zhang,et al.  An exploratory study of articular cartilage and subchondral bone reconstruction with bone marrow mesenchymal stem cells combined with porous tantalum/Bio-Gide collagen membrane in osteonecrosis of the femoral head. , 2019, Materials science & engineering. C, Materials for biological applications.

[103]  C. Pan,et al.  The effects of a functionally-graded scaffold and bone marrow-derived mononuclear cells on steroid-induced femoral head osteonecrosis. , 2018, Biomaterials.

[104]  J. Guan,et al.  Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head , 2018, Cellular Physiology and Biochemistry.

[105]  Xiaofeng Jia,et al.  Three-dimensional (3D) printed scaffold and material selection for bone repair. , 2019, Acta biomaterialia.

[106]  L. Nie,et al.  Injectable temperature-sensitive hydrogel with VEGF loaded microspheres for vascularization and bone regeneration of femoral head necrosis , 2018, Materials Letters.

[107]  S. Papapoulos,et al.  Bone Morphogenetic Proteins Stimulate Angiogenesis through Osteoblast-Derived Vascular Endothelial Growth Factor A. , 2002, Endocrinology.

[108]  Peng Zhang,et al.  Porous composite scaffold incorporating osteogenic phytomolecule icariin for promoting skeletal regeneration in challenging osteonecrotic bone in rabbits. , 2018, Biomaterials.

[109]  W. Luo,et al.  A Rabbit Model of Hormone-induced Early Avascular Necrosis of the Femoral Head , 2008, Biomedical and Environmental Sciences.

[110]  Jie Tian,et al.  Multiscale Stem Cell Technologies for Osteonecrosis of the Femoral Head , 2019, Stem cells international.

[111]  D. Hao,et al.  The genus Epimedium: an ethnopharmacological and phytochemical review. , 2011, Journal of ethnopharmacology.

[112]  Lindsay S. Wray,et al.  Arrayed Hollow Channels in Silk‐Based Scaffolds Provide Functional Outcomes for Engineering Critically Sized Tissue Constructs , 2014, Advanced functional materials.

[113]  W. Liu,et al.  A pH-Triggered, Self-Assembled, and Bioprintable Hybrid Hydrogel Scaffold for Mesenchymal Stem Cell Based Bone Tissue Engineering , 2019, ACS applied materials & interfaces.

[114]  R. Tuan,et al.  Stem cell- and growth factor-based regenerative therapies for avascular necrosis of the femoral head , 2012, Stem Cell Research & Therapy.

[115]  J. Griffith,et al.  Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid‐Associated Osteonecrosis in Rabbits , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[116]  P. Hernigou,et al.  Osteonecrosis repair with bone marrow cell therapies: state of the clinical art. , 2015, Bone.

[117]  Yan Jin,et al.  Stem cell-based bone regeneration in diseased microenvironments: Challenges and solutions. , 2017, Biomaterials.

[118]  Y. Shiozawa,et al.  Erythropoietin mediated bone formation is regulated by mTOR signaling , 2012, Journal of cellular biochemistry.

[119]  J. Planell,et al.  Role of porosity and pore architecture in the in vivo bone regeneration capacity of biodegradable glass scaffolds. , 2014, Journal of biomedical materials research. Part A.

[120]  Zhouyuan Yang,et al.  Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of the femoral head using a porous nano-lithium-hydroxyapatite/gelatin microsphere/erythropoietin composite scaffold. , 2018, Biomaterials science.

[121]  Y. Shanjani,et al.  Customized, degradable, functionally graded scaffold for potential treatment of early stage osteonecrosis of the femoral head , 2018, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[122]  Jiang Peng,et al.  Osteogenic magnesium incorporated into PLGA/TCP porous scaffold by 3D printing for repairing challenging bone defect. , 2019, Biomaterials.

[123]  M. Stiehler,et al.  Icariin Promotes Angiogenic Differentiation and Prevents Oxidative Stress‐Induced Autophagy in Endothelial Progenitor Cells , 2015, Stem cells.

[124]  Y. Iwamoto,et al.  Dose Effects of Corticosteroids on the Development of Osteonecrosis in Rabbits , 2008, The Journal of Rheumatology.

[125]  Jian Yang,et al.  Citrate-based Biodegradable Injectable hydrogel Composites for Orthopedic Applications. , 2013, Biomaterials science.

[126]  W. Wu,et al.  Emerging roles of MicroRNAs in osteonecrosis of the femoral head , 2018, Cell proliferation.

[127]  P. Touzopoulos,et al.  Use of demineralized bone matrix in spinal fusion. , 2014, World journal of orthopedics.

[128]  Zong-ke Zhou,et al.  Repairing defect and preventing collapse of femoral head in a steroid-induced osteonecrotic of femoral head animal model using strontium-doped calcium polyphosphate combined BM-MNCs , 2015, Journal of Materials Science: Materials in Medicine.

[129]  A. Mehta,et al.  Impact of sphingolipids on osteoblast and osteoclast activity in Gaucher disease. , 2018, Molecular genetics and metabolism.

[130]  Bin Ding,et al.  3D Superelastic Scaffolds Constructed from Flexible Inorganic Nanofibers with Self‐Fitting Capability and Tailorable Gradient for Bone Regeneration , 2019, Advanced Functional Materials.

[131]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[132]  A. Boccaccini,et al.  Tissue engineering of electrically responsive tissues using polyaniline based polymers: a review. , 2014, Biomaterials.

[133]  Niklas Sandler,et al.  Vascularized 3D printed scaffolds for promoting bone regeneration. , 2019, Biomaterials.

[134]  Y. Tabata,et al.  Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels. , 2014, Biomaterials.

[135]  Jiahong Meng,et al.  PTH[1-34] improves the effects of core decompression in early-stage steroid-associated osteonecrosis model by enhancing bone repair and revascularization , 2017, PloS one.

[136]  Y. Huang,et al.  Porous Tantalum Coatings Prepared by Vacuum Plasma Spraying Enhance BMSCs Osteogenic Differentiation and Bone Regeneration In Vitro and In Vivo , 2013, PloS one.

[137]  F. Pei,et al.  Lithium Chloride Modulates Adipogenesis and Osteogenesis of Human Bone Marrow-Derived Mesenchymal Stem Cells , 2015, Cellular Physiology and Biochemistry.

[138]  Y. Leng,et al.  Biofabrication of a PLGA–TCP‐based porous bioactive bone substitute with sustained release of icaritin , 2015, Journal of tissue engineering and regenerative medicine.

[139]  Xiuzhen Zhang,et al.  In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head. , 2016, Materials science & engineering. C, Materials for biological applications.

[140]  J. Parvizi,et al.  Can local Erythropoietin administration enhance bone regeneration in osteonecrosis of femoral head? , 2012, Medical hypotheses.

[141]  Xuesong Wang,et al.  Engineering Porous β-Tricalcium Phosphate (β-TCP) Scaffolds with Multiple Channels to Promote Cell Migration, Proliferation, and Angiogenesis. , 2019, ACS applied materials & interfaces.

[142]  H. Jing,et al.  Erythropoietin Promotes the Protective Properties of Transplanted Endothelial Progenitor Cells Against Acute Lung Injury via PI3K/Akt Pathway , 2014, Shock.

[143]  Xiang Wang,et al.  Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats , 2018, Cellular Physiology and Biochemistry.

[144]  K. Guo,et al.  The influence of age, gender and treatment with steroids on the incidence of osteonecrosis of the femoral head during the management of severe acute respiratory syndrome: a retrospective study. , 2014, The bone & joint journal.

[145]  H. L. Roh,et al.  Decreased Osteogenic Differentiation of Mesenchymal Stem Cells in Alcohol-induced Osteonecrosis , 2005, Clinical Orthopaedics and Related Research.

[146]  M. Chaud,et al.  Safety and efficacy of hydroxyapatite scaffold in the prevention of jaw osteonecrosis in vivo. , 2018, Journal of biomedical materials research. Part B, Applied biomaterials.

[147]  M. Ochi,et al.  Bone-marrow-derived mononuclear cells with a porous hydroxyapatite scaffold for the treatment of osteonecrosis of the femoral head: a preliminary study. , 2010, The Journal of bone and joint surgery. British volume.

[148]  A. Kaye,et al.  Stem Cell Therapy for Osteonecrosis of the Femoral Head: Current Trends and Comprehensive Review , 2018, Current Pain and Headache Reports.

[149]  G. Lin,et al.  A novel bone targeting delivery system carrying phytomolecule icaritin for prevention of steroid-associated osteonecrosis in rats. , 2018, Bone.

[150]  Sujit Kumar Tripathy,et al.  Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study. , 2012, The Journal of arthroplasty.

[151]  C. Laurencin,et al.  Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications. , 2014, Drug discovery today.

[152]  I. Martin,et al.  Engineering of large osteogenic grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose tissue. , 2011, Biomaterials.

[153]  Gwo‐Jaw Wang,et al.  Controlled-release of rhBMP-2 carriers in the regeneration of osteonecrotic bone. , 2009, Biomaterials.

[154]  L. Jiang,et al.  The application of PRP combined with TCP in repairing avascular necrosis of the femoral head after femoral neck fracture in rabbit. , 2018, European review for medical and pharmacological sciences.

[155]  I. Martin,et al.  Prefabrication of a large pedicled bone graft by engineering the germ for de novo vascularization and osteoinduction. , 2019, Biomaterials.

[156]  Molly M. Stevens,et al.  Highly porous scaffolds of PEDOT:PSS for bone tissue engineering , 2017, Acta biomaterialia.

[157]  Bo Li,et al.  In vivo pharmacokinetics comparisons of icariin, emodin and psoralen from gan-kang granules and extracts of herba Epimedii, Nepal dock root, Ficus hirta yahl. , 2009, Journal of ethnopharmacology.