Research progress on medical devices of polyhydroxyalkanoate in orthopedics_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

 WEI Daixu ^1,2 , TAN Youguo ¹

1. Zigong Affiliated Hospital of Southwest Medical University, Zigong Psychiatric Research Center, Zigong Institute of Brain Science, Zigong Sichuan, 643002, P. R. China;
2. Department of Life Sciences and Medicine, Northwest University, Xi’an Shaanxi, 710069, P. R. China;

Corresponding author：

WEI Daixu, Email: daviddxwei@163.com

Keywords：

Polyhydroxyalkanoate; 3-hydroxybutyrate; biomaterial; bone tissue engineering

DOI：

10.7507/1002-1892.202211018

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To review the research progress of natural biomaterial polyhydroxyalkanoate (PHA) in orthopedics. Methods The literature concerning PHA devices for bone defects, bone repair, and bone neoplasms, respectively, in recent years was extensively consulted. The three aspects of the advantages of PHA in bone repair, the preparation of PHA medical devices for bone repair and their application in orthopedics were discussed. Results Due to excellent biodegradability, biocompatibility, and potential osteoinduction, PHA is a kind of good bone repair material. In addition to the traditional PHA medical implants, the use of electrostatic spinning and three-dimensional printing can be designed to various functional PHA medical devices, in order to meet the orthopedic clinical demands, including the bone regeneration, minimally invasive bone tissue repair by injection, antibacterial bone repair, auxiliary establishment of three-dimensional bone tumor model, directed osteogenic differentiation of stem cells, etc. Conclusion At present, PHA is a hotspot of biomaterials for translational medicine in orthopedics. Although they have not completely applied in the clinic, the advantages of repair in bone defects have been gradually reflected in tissue engineering, showing an application prospect in orthopedics.

Citation： WEI Daixu, TAN Youguo. Research progress on medical devices of polyhydroxyalkanoate in orthopedics. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(8): 909-917. doi: 10.7507/1002-1892.202211018 Copy

1.	Porter JR, Ruckh TT, Popat KC. Bone tissue engineering: a review in bone biomimetics and drug delivery strategies. Biotechnol Prog, 2009, 25(6): 1539-1560.
2.	Wang ZY, Zhang XW, Ding YW, et al. Natural biopolyester microspheres with diverse structures and surface topologies as micro-devices for biomedical applications. Smart Materials in Medicine, 2023, 4: 15-36.
3.	Wu Q, Wang Y, Chen GQ. Medical application of microbial biopolyesters polyhydroxyalkanoates. Artif Cells Blood Substit Immobil Biotechnol, 2009, 37(1): 1-12.
4.	Sudesh K, Abe H, Doi Y. Synthesis, structure and properties of polyhydroxyalkanoates: biological polyesters. Progress in Polymer Science, 2000, 25(10): 1503-1555.
5.	Reddy CS, Ghai R, Rashmi None, et al. Polyhydroxyalkanoates: an overview. Bioresour Technol, 2003, 87(2): 137-146.
6.	Khanna S, Srivastava AK. Recent advances in microbial polyhydroxyalkanoates. Process Biochemistry, 2005, 40(2): 607-619.
7.	Shimamura E, Scandola M, Doi Y. Microbial synthesis and characterization of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). Macromolecules, 1994, 27(16): 4429-4435.
8.	Eggink G, de Waard P, Huijberts GN. Formation of novel poly(hydroxyalkanoates) from long-chain fatty acids. Can J Microbiol, 1995, 41 Suppl 1: 14-21.
9.	Zhao XH, Niu YN, Mi CH, et al. Electrospinning nanofibers of microbial polyhydroxyalkanoates for applications in medical tissue engineering. Journal of Polymer Science, 2021, 59(18): 1994-2013.
10.	Xiang Y, Wang QQ, Lan XQ, et al. Function and treatment strategies of β-hydroxybutyrate in aging. Smart Materials in Medicine, 2023, 4: 160-172.
11.	Sun G, Wei D, Liu X, et al. Novel biodegradable electrospun nanofibrous P(DLLA-CL) balloons for the treatment of vertebral compression fractures. Nanomedicine, 2013, 9(6): 829-838.
12.	Peng XL, Cheng JS, Gong HL, et al. Advances in the design and development of SARS-CoV-2 vaccines. Mil Med Res, 2021, 8(1): 67. doi: 10.1186/s40779-021-00360-1.
13.	Townsend KJ, Busse K, Kressler J, et al. Contact angle, WAXS, and SAXS analysis of poly(beta-hydroxybutyrate) and poly(ethylene glycol) block copolymers obtained via Azotobacter vinelandii UWD. Biotechnol Prog, 2005, 21(3): 959-964.
14.	Sequeira RA, Dubey S, Pereira MM, et al. Neoteric solvent systems as sustainable media for dissolution and film preparation of poly-[(R)-3-hydroxybutyrate]. ACS Sustainable Chemistry & Engineering, 2020, 8(32): 12005-12013.
15.	Yamashita K, Yamada M, Numata K, et al. Nonspecific hydrophobic interactions of a repressor protein, PhaR, with poly[(R)-3-hydroxybutyrate] film studied with a quartz crystal microbalance. Biomacromolecules, 2006, 7(8): 2449-2454.
16.	Zhao W, Chen GQ. Production and characterization of terpolyester poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) by recombinant aeromonas hydrophila 4AK4 harboring genes phaAB. Process Biochemistry, 2007, 42(9): 1342-1347.
17.	Yu HY, Qin ZY, Wang LF, et al. Crystallization behavior and hydrophobic properties of biodegradable ethyl cellulose-g-poly (3-hydroxybutyrate-co-3-hydroxyvalerate): The influence of the side-chain length and grafting density. Carbohydrate Polymers, 2012, 87(4): 2447-2454.
18.	Bianco A, Calderone M, Cacciotti I. Electrospun PHBV/PEO co-solution blends: microstructure, thermal and mechanical properties. Mater Sci Eng C Mater Biol Appl, 2013, 33(3): 1067-1077.
19.	Wang H, Watanabe H, Ogita M, et al. Effect of human beta-defensin-3 on the proliferation of fibroblasts on periodontally involved root surfaces. Peptides, 2011, 32(5): 888-894.
20.	Sadat-Shojai M, Moghaddas H. Modulated composite nanofibers with enhanced structural stability for promotion of hard tissue healing. Iranian Journal of Science and Technology, Transactions A:Science, 2021, 45(2): 529-537.
21.	Wang Y, Lu L, Zheng Y, et al. Improvement in hydrophilicity of PHBV films by plasma treatment. J Biomed Mater Res A, 2006, 76(3): 589-595.
22.	Wu LP, You ML, Wang DY, et al. Fabrication of carbon nanotube (CNT)/poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) nanocomposite films for human mesenchymal stem cell (hMSC) differentiation. Polymer Chemistry, 2013, 4(16): 4490-4498.
23.	Fu N, Xie J, Li G, et al. P34HB film promotes cell adhesion, in vitro proliferation, and in vivo cartilage repair. RSC Advances, 2015, 5(28): 21572-21579.
24.	Li W, Cicek N, Levin DB, et al. Bacteria-triggered release of a potent biocide from core-shell polyhydroxyalkanoate (PHA)-based nanofibers for wound dressing applications. J Biomater Sci Polym Ed, 2020, 31(3): 394-406.
25.	Sun XM, Zhong LH, Lan XP, et al. The compatibility of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and thermoplastic polyurethane blends. AMR, 2013, 815: 552-557.
26.	Wang XP, Li WF, Zhang H, et al. Effect of sodium benzoate on the crystallization behavior of poly (3-hydroxybutyrate-co-4-hydroxybutyrate). AMM, 2014, 665: 375-378.
27.	Yu Y, Li Y, Han C, et al. Enhancement of the properties of biosourced poly(3-hydroxybutyrate-co-4-hydroxybutyrate) by the incorporation of natural orotic acid. Int J Biol Macromol, 2019, 136: 764-773.
28.	Hu YJ, Wei X, Zhao W, et al. Biocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) with bone marrow mesenchymal stem cells. Acta Biomater, 2009, 5(4): 1115-1125.
29.	Wang Y, Jiang XL, Peng SW, et al. Induced apoptosis of osteoblasts proliferating on polyhydroxyalkanoates. Biomaterials, 2013, 34(15): 3737-3746.
30.	Ye HM, Wang Z, Wang HH, et al. Different thermal behaviors of microbial polyesters poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). Polymer, 2010, 51(25): 6037-6046.
31.	Wang YW, Mo W, Yao H, et al. Biodegradation studies of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). Polymer Degradation and Stability, 2004, 85(2): 815-821.
32.	Qu XH, Wu Q, Zhang KY, et al. In vivo studies of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) based polymers: biodegradation and tissue reactions. Biomaterials, 2006, 27(19): 3540-3548.
33.	Wei DX, Dao JW, Chen GQ. A micro-ark for cells: Highly open porous polyhydroxyalkanoate microspheres as injectable scaffolds for tissue regeneration. Adv Mater, 2018, 30(31): e1802273. doi: 10.1002/adma.201802273.
34.	Singh AK, Srivastava JK, Chandel AK, et al. Biomedical applications of microbially engineered polyhydroxyalkanoates: an insight into recent advances, bottlenecks, and solutions. Appl Microbiol Biotechnol, 2019, 103(5): 2007-2032.
35.	Xu N, Peng XL, Li HR, et al. Marine-derived collagen as biomaterials for human health. Front Nutr, 2021, 8: 702108. doi: 10.3389/fnut.2021.702108.
36.	Liu X, Wei D, Zhong J, et al. Electrospun nanofibrous P(DLLA-CL) balloons as calcium phosphate cement filled containers for bone repair: in vitro and in vivo studies. ACS Appl Mater Interfaces, 2015, 7(33): 18540-18552.
37.	Liu HW, Wei DX, Deng JZ, et al. Combined antibacterial and osteogenic in situ effects of a bifunctional titanium alloy with nanoscale hydroxyapatite coating. Artif Cells Nanomed Biotechnol, 2018, 46(sup3): S460-S470.
38.	Shen F, Zhang E, Wei Z. In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment. Materials Science and Engineering:C, 2010, 30(3): 369-375.
39.	Peng SW, Guo XY, Shang GG, et al. An assessment of the risks of carcinogenicity associated with polyhydroxyalkanoates through an analysis of DNA aneuploid and telomerase activity. Biomaterials, 2011, 32(10): 2546-2555.
40.	Li X, Li X, Chen D, et al. Evaluating the biological impact of polyhydroxyalkanoates (PHAs) on developmental and exploratory profile of zebrafish larvae. RSC advances, 2016, 6(43): 37018-37030.
41.	Ji Y, Li XT, Chen GQ. Interactions between a poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) terpolyester and human keratinocytes. Biomaterials, 2008, 29(28): 3807-3814.
42.	Böstman O. Absorbable implants for the fixation of fractures. JBJS, 1991, 73(1): 148-153.
43.	Zhao Y, Zou B, Shi Z, et al. The effect of 3-hydroxybutyrate on the in vitro differentiation of murine osteoblast MC3T3-E1 and in vivo bone formation in ovariectomized rats. Biomaterials, 2007, 28(20): 3063-3073.
44.	Cheng S, Wu Q, Yang F, et al. Influence of DL-beta-hydroxybutyric acid on cell proliferation and calcium influx. Biomacromolecules, 2005, 6(2): 593-597.
45.	Rahman M, Peng XL, Zhao XH, et al. 3D bioactive cell-free-scaffolds for in-vitro/in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration. Bioact Mater, 2021, 6(11): 4083-4095.
46.	Wei D, Qiao R, Dao J, et al. Soybean lecithin-mediated nanoporous PLGA microspheres with highly entrapped and controlled released BMP-2 as a stem cell platform. Small, 2018, 14(22): e1800063. doi: 10.1002/smll.201800063.
47.	Chen R, Yu J, Gong HL, et al. An easy long-acting BMP7 release system based on biopolymer nanoparticles for inducing osteogenic differentiation of adipose mesenchymal stem cells. J Tissue Eng Regen Med, 2020, 14(7): 964-972.
48.	Luklinska ZB, Schluckwerder H. In vivo response to HA-polyhydroxybutyrate/polyhydroxyvalerate composite. J Microsc, 2003, 211(Pt 2): 121-129.
49.	Rodrigues AA, Batista NA, Malmonge SM, et al. Osteogenic differentiation of rat bone mesenchymal stem cells cultured on poly (hydroxybutyrate-co-hydroxyvalerate), poly (ε-caprolactone) scaffolds. J Mater Sci Mater Med, 2021, 32(11): 138. doi: 10.1007/s10856-021-06615-6.
50.	Wu J, Wu Z, Xue Z, et al. PHBV/bioglass composite scaffolds with co-cultures of endothelial cells and bone marrow stromal cells improve vascularization and osteogenesis for bone tissue engineering. RSC Advances, 2017, 7(36): 22197-22207.
51.	Sadat-Shojai M, Khorasani MT, Jamshidi A, et al. Nano-hydroxyapatite reinforced polyhydroxybutyrate composites: a comprehensive study on the structural and in vitro biological properties. Mater Sci Eng C Mater Biol Appl, 2013, 33(5): 2776-2787.
52.	Misra SK, Mohn D, Brunner TJ, et al. Comparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/Bioglass composites. Biomaterials, 2008, 29(12): 1750-1761.
53.	Chen Z, Song Y, Zhang J, et al. Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering. Mater Sci Eng C Mater Biol Appl, 2017, 72: 341-351.
54.	Toloue EB, Karbasi S, Salehi H, et al. Potential of an electrospun composite scaffold of poly (3-hydroxybutyrate)-chitosan/alumina nanowires in bone tissue engineering applications. Mater Sci Eng C Mater Biol Appl, 2019, 99: 1075-1091.
55.	Zarei M, Karbasi S. Evaluation of the effects of multiwalled carbon nanotubes on electrospun poly (3-hydroxybutirate) scaffold for tissue engineering applications. Journal of Porous Materials, 2018, 25(1): 259-272.
56.	Liu KL, Choo ES, Wong SY, et al. Designing poly [(R)-3-hydroxybutyrate]-based polyurethane block copolymers for electrospun nanofiber scaffolds with improved mechanical properties and enhanced mineralization capability. J Phys Chem B, 2010, 114(22): 7489-7498.
57.	Karbowniczek JE, Kaniuk Ł, Berniak K, et al. Enhanced cells anchoring to electrospun hybrid scaffolds with PHBV and HA particles for bone tissue regeneration. Front Bioeng Biotechnol, 2021, 9: 632029. doi: 10.3389/fbioe.2021.632029.
58.	Nemati Hatati A, Hosseinalipour SM, Rezaie HR, et al. Characterization of poly (3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds fabricated without the use of organic solvents for bone tissue engineering applications. Materials Science and Engineering:C, 2012, 32(3): 416-222.
59.	Zheng Y, Wang Y, Yang H, et al. Characteristic comparison of bioactive scaffolds based on polyhydroxyalkoanate/bioceramic hybrids. J Biomed Mater Res B Appl Biomater, 2007, 80(1): 236-243.
60.	Baek JY, Xing ZC, Kwak G, et al. Fabrication and characterization of collagen-immobilized porous PHBV/HA nanocomposite scaffolds for bone tissue engineering. Journal of Nanomaterials, 2012, 2012: e171804. doi: 10.1155/2012/171804.
61.	Ye X, Li L, Lin Z, et al. Integrating 3D-printed PHBV/Calcium sulfate hemihydrate scaffold and chitosan hydrogel for enhanced osteogenic property. Carbohydr Polym, 2018, 202: 106-114.
62.	Shuai C, Wang C, Qi F, et al. Enhanced crystallinity and antibacterial of PHBV scaffolds incorporated with zinc oxide. Journal of Nanomaterials, 2020. doi: 10.1155/2020/6014816.
63.	Ye X, Zhang Y, Liu T, et al. Beta-tricalcium phosphate enhanced mechanical and biological properties of 3D-printed polyhydroxyalkanoates scaffold for bone tissue engineering. Int J Biol Macromol, 2022, 209(Pt A): 1553-1561.
64.	Yang S, Wang J, Tang L, et al. Mesoporous bioactive glass doped-poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) composite scaffolds with 3-dimensionally hierarchical pore networks for bone regeneration. Colloids Surf B Biointerfaces, 2014, 116: 72-80.
65.	Zhao S, Zhu M, Zhang J, et al. Three dimensionally printed mesoporous bioactive glass and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) composite scaffolds for bone regeneration. J Mater Chem B, 2014, 2(36): 6106-6118.
66.	Boeree NR, Dove J, Cooper JJ, et al. Development of a degradable composite for orthopaedic use: mechanical evaluation of an hydroxyapatite-polyhydroxybutyrate composite material. Biomaterials, 1993, 14(10): 793-796.
67.	Czechowska J, Skibiński S, Guzik M, et al. Silver decorated βTCP-poly (3hydroxybutyrate) scaffolds for bone tissue engineering. Materials (Basel), 2021, 14(15): 4227. doi: 10.3390/ma14154227.
68.	Yuan S, Shen Y, Li Z. Injectable cell- and growth factor-free poly(4-hydroxybutyrate) (P4HB) microspheres with open porous structures and great efficiency of promoting bone regeneration. ACS Appl Bio Mater, 2021, 4(5): 4432-4440.
69.	Chotchindakun K, Pekkoh J, Ruangsuriya J, et al. Fabrication and characterization of cinnamaldehyde-loaded mesoporous bioactive glass nanoparticles/PHBV-based microspheres for preventing bacterial infection and promoting bone tissue regeneration. Polymers (Basel), 2021, 13(11): 1794. doi: 10.3390/polym13111794.
70.	Zhao XH, Peng XL, Gong HL, et al. Osteogenic differentiation system based on biopolymer nanoparticles for stem cells in simulated microgravity. Biomed Mater, 2021, 16(4): 044102. doi: 10.1088/1748-605X/abe9d1.
71.	Almeida Neto GR, Barcelos MV, Ribeiro MEA, et al. Formulation and characterization of a novel PHBV nanocomposite for bone defect filling and infection treatment. Mater Sci Eng C Mater Biol Appl, 2019, 104: 110004. doi: 10.1016/j.msec.2019.110004.
72.	Li XT, Zhang Y, Chen GQ. Nanofibrous polyhydroxyalkanoate matrices as cell growth supporting materials. Biomaterials, 2008, 29(27): 3720-3728.
73.	Kong I, Tshai K, Hoque ME. Manufacturing of natural fibre-reinforced polymer composites by solvent casting method//Salit M, Jawaid M, Yusoff N, et al. Manufacturing of natural fibre reinforced polymer composites. Cham: Springer, 2015: 331-349.
74.	Hou Q, Grijpma DW, Feijen J. Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique. Biomaterials, 2003, 24(11): 1937-1947.
75.	Sodian R, Hoerstrup SP, Sperling JS, et al. Evaluation of biodegradable, three-dimensional matrices for tissue engineering of heart valves. ASAIO J, 2000, 46(1): 107-110.
76.	Wang YW, Wu Q, Chen GQ. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. Biomaterials, 2004, 25(4): 669-675.
77.	Sodian R, Hoerstrup SP, Sperling JS, et al. Early in vivo experience with tissue-engineered trileaflet heart valves. Circulation, 2000, 102(19 Suppl 3): 22-29.
78.	Wei DX, Dao JW, Liu HW, et al. Suspended polyhydroxyalkanoate microspheres as 3D carriers for mammalian cell growth. Artif Cells Nanomed Biotechnol, 2018, 46(sup2): 473-483.
79.	魏岱旭, 李腾, 张浩千, 等. 一种窄粒度分布的聚羟基脂肪酸酯微球及其制备方法: 中国, CN113617305B [P/OL]. 2021-11-09.
80.	CHOINIERE P. Development of polyhydroxyalkanoate nanoparticles for cancer therapy[OL]. [2023-02-03] https://www.semanticscholar.org/paper/Development-of-Polyhydroxyalkanoate-Nanoparticles-Choiniere/5f1ce1cd80a37a5552db0dc80888f98bdce077c4#citing-papers.
81.	Samrot AV, Samanvitha SK, Shobana N, et al. The synthesis, characterization and applications of polyhydroxyalkanoates (PHAs) and PHA-based nanoparticles. Polymers (Basel), 2021, 13(19): 3302.
82.	Peprah BA, Ramsay JA, Ramsay BA. Dense stable suspensions of medium-chain-length poly (3-hydroxyalkanoate) nanoparticles. European Polymer Journal, 2016, 84: 137-146.
83.	Deepak V, Pandian Sb, Kalishwaralal K, et al. Purification, immobilization, and characterization of nattokinase on PHB nanoparticles. Bioresour Technol, 2009, 100(24): 6644-6646.
84.	Vilos C, Morales FA, Solar PA, et al. Paclitaxel-PHBV nanoparticles and their toxicity to endometrial and primary ovarian cancer cells. Biomaterials, 2013, 34(16): 4098-4108.
85.	Kılıçay E, Demirbilek M, Türk M, et al. Preparation and characterization of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy. Eur J Pharm Sci, 2011, 44(3): 310-320.
86.	Gossmann R, Langer K, Mulac D. New perspective in the formulation and characterization of didodecyldimethylammonium bromide (DMAB) stabilized poly(lactic-co-glycolic acid) (PLGA) nanoparticles. PLoS One, 2015, 10(7): e0127532. doi: 10.1371/journal.pone.0127532.
87.	Lu XY, Ciraolo E, Stefenia R, et al. Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines. Appl Microbiol Biotechnol, 2011, 89(5): 1423-1433.
88.	Knowles JC. Development of a natural degradable polymer for orthopaedic use. J Med Eng Technol, 1993, 17(4): 129-137.
89.	Doyle C, Tanner ET, Bonfield W. In vitro and in vivo evaluation of polyhydroxybutyrate and of polyhydroxybutyrate reinforced with hydroxyapatite. Biomaterials, 1991, 12(9): 841-847.
90.	Luklinska ZB, Bonfield W. Morphology and ultrastructure of the interface between hydroxyapatite-polyhydroxybutyrate composite implant and bone. J Mater Sci Mater Med, 1997, 8(6): 379-383.
91.	Bernd HE, Kunze C, Freier T, et al. Poly (3-hydroxybutyrate) (PHB) patches for covering anterior skull base defects-an animal study with minipigs. Acta Otolaryngol, 2009, 129(9): 1010-1017.
92.	Köse GT, Ber S, Korkusuz F, et al. Poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) based tissue engineering matrices. J Mater Sci Mater Med, 2003, 14(2): 121-126.
93.	Wang YW, Wu Q, Chen J, et al. Evaluation of three-dimensional scaffolds made of blends of hydroxyapatite and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) for bone reconstruction. Biomaterials, 2005, 26(8): 899-904.
94.	Wang Y, Gao R, Wang PP, et al. The differential effects of aligned electrospun PHBHHx fibers on adipogenic and osteogenic potential of MSCs through the regulation of PPARγ signaling. Biomaterials, 2012, 33(2): 485-493.
95.	Wang Y, Jiang XL, Yang SC, et al. MicroRNAs in the regulation of interfacial behaviors of MSCs cultured on microgrooved surface pattern. Biomaterials, 2011, 32(35): 9207-9217.
96.	Wei X, Hu YJ, Xie WP, et al. Influence of poly (3-hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyhexanoate) on growth and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. J Biomed Mater Res A, 2009, 90(3): 894-905.
97.	Shishatskaya EI, Khlusov IA, Volova TG. A hybrid PHB-hydroxyapatite composite for biomedical application: production, in vitro and in vivo investigation. J Biomater Sci Polym Ed, 2006, 17(5): 481-498.
98.	Degli Esposti M, Chiellini F, Bondioli F, et al. Highly porous PHB-based bioactive scaffolds for bone tissue engineering by in situ synthesis of hydroxyapatite. Mater Sci Eng C Mater Biol Appl, 2019, 100: 286-296.
99.	Sadat-Shojai M, Khorasani MT, Jamshidi A. A new strategy for fabrication of bone scaffolds using electrospun nano-HAp/PHB fibers and protein hydrogels. Chemical Engineering Journal, 2016, 289: 38-47.
100.	Yu J, Xu N, Xi Y, et al. Adhesion behavior of escherichia coli on plasma-sprayed Zn and Ag co-incorporated calcium silicate coatings with varying surface roughness. Journal of Thermal Spray Technology, 2018, 27(8): 1428-1435.
101.	Fan L, Xie J, Zheng Y, et al. Antibacterial, Self-adhesive, recyclable, and tough conductive composite hydrogels for ultrasensitive strain sensing. ACS Appl Mater Interfaces, 2020, 12(19): 22225-22236.
102.	Fan L, Hu L, Xie J, et al. Biosafe, self-adhesive, recyclable, tough, and conductive hydrogels for multifunctional sensors. Biomater Sci, 2021, 9(17): 5884-5896.
103.	Fan L, He Z, Peng X, et al. Injectable, intrinsically antibacterial conductive hydrogels with self-healing and pH stimulus responsiveness for epidermal sensors and wound healing. ACS Appl Mater Interfaces, 2021, 13(45): 53541-53552.
104.	Wei DX, Zhang XW. Biosynthesis, bioactivity, biosafety and applications of antimicrobial peptides for human health. Biosafety and Health, 2022. doi: 10.1016/j.bsheal.2022.02.003.
105.	魏岱旭, 龚海伦, 张旭维. 抗菌肽的生物合成及医学应用. 合成生物学, 2022, 3(4): 709-727.
106.	Ding YW, Zhang XW, Mi CH, et al. Recent advances in hyaluronic acid-based hydrogels for 3D bioprinting in tissue engineering applications. Smart Materials in Medicine, 2023, 4: 59-68.
107.	Ding YW, Wang ZY, Ren ZW, et al. Advances in modified hyaluronic acid-based hydrogels for skin wound healing. Biomater Sci, 2022, 10(13): 3393-3409.

1. Porter JR, Ruckh TT, Popat KC. Bone tissue engineering: a review in bone biomimetics and drug delivery strategies. Biotechnol Prog, 2009, 25(6): 1539-1560.
2. Wang ZY, Zhang XW, Ding YW, et al. Natural biopolyester microspheres with diverse structures and surface topologies as micro-devices for biomedical applications. Smart Materials in Medicine, 2023, 4: 15-36.
3. Wu Q, Wang Y, Chen GQ. Medical application of microbial biopolyesters polyhydroxyalkanoates. Artif Cells Blood Substit Immobil Biotechnol, 2009, 37(1): 1-12.
4. Sudesh K, Abe H, Doi Y. Synthesis, structure and properties of polyhydroxyalkanoates: biological polyesters. Progress in Polymer Science, 2000, 25(10): 1503-1555.
5. Reddy CS, Ghai R, Rashmi None, et al. Polyhydroxyalkanoates: an overview. Bioresour Technol, 2003, 87(2): 137-146.
6. Khanna S, Srivastava AK. Recent advances in microbial polyhydroxyalkanoates. Process Biochemistry, 2005, 40(2): 607-619.
7. Shimamura E, Scandola M, Doi Y. Microbial synthesis and characterization of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). Macromolecules, 1994, 27(16): 4429-4435.
8. Eggink G, de Waard P, Huijberts GN. Formation of novel poly(hydroxyalkanoates) from long-chain fatty acids. Can J Microbiol, 1995, 41 Suppl 1: 14-21.
9. Zhao XH, Niu YN, Mi CH, et al. Electrospinning nanofibers of microbial polyhydroxyalkanoates for applications in medical tissue engineering. Journal of Polymer Science, 2021, 59(18): 1994-2013.
10. Xiang Y, Wang QQ, Lan XQ, et al. Function and treatment strategies of β-hydroxybutyrate in aging. Smart Materials in Medicine, 2023, 4: 160-172.
11. Sun G, Wei D, Liu X, et al. Novel biodegradable electrospun nanofibrous P(DLLA-CL) balloons for the treatment of vertebral compression fractures. Nanomedicine, 2013, 9(6): 829-838.
12. Peng XL, Cheng JS, Gong HL, et al. Advances in the design and development of SARS-CoV-2 vaccines. Mil Med Res, 2021, 8(1): 67. doi: 10.1186/s40779-021-00360-1.
13. Townsend KJ, Busse K, Kressler J, et al. Contact angle, WAXS, and SAXS analysis of poly(beta-hydroxybutyrate) and poly(ethylene glycol) block copolymers obtained via Azotobacter vinelandii UWD. Biotechnol Prog, 2005, 21(3): 959-964.
14. Sequeira RA, Dubey S, Pereira MM, et al. Neoteric solvent systems as sustainable media for dissolution and film preparation of poly-[(R)-3-hydroxybutyrate]. ACS Sustainable Chemistry & Engineering, 2020, 8(32): 12005-12013.
15. Yamashita K, Yamada M, Numata K, et al. Nonspecific hydrophobic interactions of a repressor protein, PhaR, with poly[(R)-3-hydroxybutyrate] film studied with a quartz crystal microbalance. Biomacromolecules, 2006, 7(8): 2449-2454.
16. Zhao W, Chen GQ. Production and characterization of terpolyester poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) by recombinant aeromonas hydrophila 4AK4 harboring genes phaAB. Process Biochemistry, 2007, 42(9): 1342-1347.
17. Yu HY, Qin ZY, Wang LF, et al. Crystallization behavior and hydrophobic properties of biodegradable ethyl cellulose-g-poly (3-hydroxybutyrate-co-3-hydroxyvalerate): The influence of the side-chain length and grafting density. Carbohydrate Polymers, 2012, 87(4): 2447-2454.
18. Bianco A, Calderone M, Cacciotti I. Electrospun PHBV/PEO co-solution blends: microstructure, thermal and mechanical properties. Mater Sci Eng C Mater Biol Appl, 2013, 33(3): 1067-1077.
19. Wang H, Watanabe H, Ogita M, et al. Effect of human beta-defensin-3 on the proliferation of fibroblasts on periodontally involved root surfaces. Peptides, 2011, 32(5): 888-894.
20. Sadat-Shojai M, Moghaddas H. Modulated composite nanofibers with enhanced structural stability for promotion of hard tissue healing. Iranian Journal of Science and Technology, Transactions A:Science, 2021, 45(2): 529-537.
21. Wang Y, Lu L, Zheng Y, et al. Improvement in hydrophilicity of PHBV films by plasma treatment. J Biomed Mater Res A, 2006, 76(3): 589-595.
22. Wu LP, You ML, Wang DY, et al. Fabrication of carbon nanotube (CNT)/poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) nanocomposite films for human mesenchymal stem cell (hMSC) differentiation. Polymer Chemistry, 2013, 4(16): 4490-4498.
23. Fu N, Xie J, Li G, et al. P34HB film promotes cell adhesion, in vitro proliferation, and in vivo cartilage repair. RSC Advances, 2015, 5(28): 21572-21579.
24. Li W, Cicek N, Levin DB, et al. Bacteria-triggered release of a potent biocide from core-shell polyhydroxyalkanoate (PHA)-based nanofibers for wound dressing applications. J Biomater Sci Polym Ed, 2020, 31(3): 394-406.
25. Sun XM, Zhong LH, Lan XP, et al. The compatibility of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and thermoplastic polyurethane blends. AMR, 2013, 815: 552-557.
26. Wang XP, Li WF, Zhang H, et al. Effect of sodium benzoate on the crystallization behavior of poly (3-hydroxybutyrate-co-4-hydroxybutyrate). AMM, 2014, 665: 375-378.
27. Yu Y, Li Y, Han C, et al. Enhancement of the properties of biosourced poly(3-hydroxybutyrate-co-4-hydroxybutyrate) by the incorporation of natural orotic acid. Int J Biol Macromol, 2019, 136: 764-773.
28. Hu YJ, Wei X, Zhao W, et al. Biocompatibility of poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) with bone marrow mesenchymal stem cells. Acta Biomater, 2009, 5(4): 1115-1125.
29. Wang Y, Jiang XL, Peng SW, et al. Induced apoptosis of osteoblasts proliferating on polyhydroxyalkanoates. Biomaterials, 2013, 34(15): 3737-3746.
30. Ye HM, Wang Z, Wang HH, et al. Different thermal behaviors of microbial polyesters poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). Polymer, 2010, 51(25): 6037-6046.
31. Wang YW, Mo W, Yao H, et al. Biodegradation studies of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate). Polymer Degradation and Stability, 2004, 85(2): 815-821.
32. Qu XH, Wu Q, Zhang KY, et al. In vivo studies of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) based polymers: biodegradation and tissue reactions. Biomaterials, 2006, 27(19): 3540-3548.
33. Wei DX, Dao JW, Chen GQ. A micro-ark for cells: Highly open porous polyhydroxyalkanoate microspheres as injectable scaffolds for tissue regeneration. Adv Mater, 2018, 30(31): e1802273. doi: 10.1002/adma.201802273.
34. Singh AK, Srivastava JK, Chandel AK, et al. Biomedical applications of microbially engineered polyhydroxyalkanoates: an insight into recent advances, bottlenecks, and solutions. Appl Microbiol Biotechnol, 2019, 103(5): 2007-2032.
35. Xu N, Peng XL, Li HR, et al. Marine-derived collagen as biomaterials for human health. Front Nutr, 2021, 8: 702108. doi: 10.3389/fnut.2021.702108.
36. Liu X, Wei D, Zhong J, et al. Electrospun nanofibrous P(DLLA-CL) balloons as calcium phosphate cement filled containers for bone repair: in vitro and in vivo studies. ACS Appl Mater Interfaces, 2015, 7(33): 18540-18552.
37. Liu HW, Wei DX, Deng JZ, et al. Combined antibacterial and osteogenic in situ effects of a bifunctional titanium alloy with nanoscale hydroxyapatite coating. Artif Cells Nanomed Biotechnol, 2018, 46(sup3): S460-S470.
38. Shen F, Zhang E, Wei Z. In vitro blood compatibility of poly (hydroxybutyrate-co-hydroxyhexanoate) and the influence of surface modification by alkali treatment. Materials Science and Engineering:C, 2010, 30(3): 369-375.
39. Peng SW, Guo XY, Shang GG, et al. An assessment of the risks of carcinogenicity associated with polyhydroxyalkanoates through an analysis of DNA aneuploid and telomerase activity. Biomaterials, 2011, 32(10): 2546-2555.
40. Li X, Li X, Chen D, et al. Evaluating the biological impact of polyhydroxyalkanoates (PHAs) on developmental and exploratory profile of zebrafish larvae. RSC advances, 2016, 6(43): 37018-37030.
41. Ji Y, Li XT, Chen GQ. Interactions between a poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) terpolyester and human keratinocytes. Biomaterials, 2008, 29(28): 3807-3814.
42. Böstman O. Absorbable implants for the fixation of fractures. JBJS, 1991, 73(1): 148-153.
43. Zhao Y, Zou B, Shi Z, et al. The effect of 3-hydroxybutyrate on the in vitro differentiation of murine osteoblast MC3T3-E1 and in vivo bone formation in ovariectomized rats. Biomaterials, 2007, 28(20): 3063-3073.
44. Cheng S, Wu Q, Yang F, et al. Influence of DL-beta-hydroxybutyric acid on cell proliferation and calcium influx. Biomacromolecules, 2005, 6(2): 593-597.
45. Rahman M, Peng XL, Zhao XH, et al. 3D bioactive cell-free-scaffolds for in-vitro/in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration. Bioact Mater, 2021, 6(11): 4083-4095.
46. Wei D, Qiao R, Dao J, et al. Soybean lecithin-mediated nanoporous PLGA microspheres with highly entrapped and controlled released BMP-2 as a stem cell platform. Small, 2018, 14(22): e1800063. doi: 10.1002/smll.201800063.
47. Chen R, Yu J, Gong HL, et al. An easy long-acting BMP7 release system based on biopolymer nanoparticles for inducing osteogenic differentiation of adipose mesenchymal stem cells. J Tissue Eng Regen Med, 2020, 14(7): 964-972.
48. Luklinska ZB, Schluckwerder H. In vivo response to HA-polyhydroxybutyrate/polyhydroxyvalerate composite. J Microsc, 2003, 211(Pt 2): 121-129.
49. Rodrigues AA, Batista NA, Malmonge SM, et al. Osteogenic differentiation of rat bone mesenchymal stem cells cultured on poly (hydroxybutyrate-co-hydroxyvalerate), poly (ε-caprolactone) scaffolds. J Mater Sci Mater Med, 2021, 32(11): 138. doi: 10.1007/s10856-021-06615-6.
50. Wu J, Wu Z, Xue Z, et al. PHBV/bioglass composite scaffolds with co-cultures of endothelial cells and bone marrow stromal cells improve vascularization and osteogenesis for bone tissue engineering. RSC Advances, 2017, 7(36): 22197-22207.
51. Sadat-Shojai M, Khorasani MT, Jamshidi A, et al. Nano-hydroxyapatite reinforced polyhydroxybutyrate composites: a comprehensive study on the structural and in vitro biological properties. Mater Sci Eng C Mater Biol Appl, 2013, 33(5): 2776-2787.
52. Misra SK, Mohn D, Brunner TJ, et al. Comparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/Bioglass composites. Biomaterials, 2008, 29(12): 1750-1761.
53. Chen Z, Song Y, Zhang J, et al. Laminated electrospun nHA/PHB-composite scaffolds mimicking bone extracellular matrix for bone tissue engineering. Mater Sci Eng C Mater Biol Appl, 2017, 72: 341-351.
54. Toloue EB, Karbasi S, Salehi H, et al. Potential of an electrospun composite scaffold of poly (3-hydroxybutyrate)-chitosan/alumina nanowires in bone tissue engineering applications. Mater Sci Eng C Mater Biol Appl, 2019, 99: 1075-1091.
55. Zarei M, Karbasi S. Evaluation of the effects of multiwalled carbon nanotubes on electrospun poly (3-hydroxybutirate) scaffold for tissue engineering applications. Journal of Porous Materials, 2018, 25(1): 259-272.
56. Liu KL, Choo ES, Wong SY, et al. Designing poly [(R)-3-hydroxybutyrate]-based polyurethane block copolymers for electrospun nanofiber scaffolds with improved mechanical properties and enhanced mineralization capability. J Phys Chem B, 2010, 114(22): 7489-7498.
57. Karbowniczek JE, Kaniuk Ł, Berniak K, et al. Enhanced cells anchoring to electrospun hybrid scaffolds with PHBV and HA particles for bone tissue regeneration. Front Bioeng Biotechnol, 2021, 9: 632029. doi: 10.3389/fbioe.2021.632029.
58. Nemati Hatati A, Hosseinalipour SM, Rezaie HR, et al. Characterization of poly (3-hydroxybutyrate)/nano-hydroxyapatite composite scaffolds fabricated without the use of organic solvents for bone tissue engineering applications. Materials Science and Engineering:C, 2012, 32(3): 416-222.
59. Zheng Y, Wang Y, Yang H, et al. Characteristic comparison of bioactive scaffolds based on polyhydroxyalkoanate/bioceramic hybrids. J Biomed Mater Res B Appl Biomater, 2007, 80(1): 236-243.
60. Baek JY, Xing ZC, Kwak G, et al. Fabrication and characterization of collagen-immobilized porous PHBV/HA nanocomposite scaffolds for bone tissue engineering. Journal of Nanomaterials, 2012, 2012: e171804. doi: 10.1155/2012/171804.
61. Ye X, Li L, Lin Z, et al. Integrating 3D-printed PHBV/Calcium sulfate hemihydrate scaffold and chitosan hydrogel for enhanced osteogenic property. Carbohydr Polym, 2018, 202: 106-114.
62. Shuai C, Wang C, Qi F, et al. Enhanced crystallinity and antibacterial of PHBV scaffolds incorporated with zinc oxide. Journal of Nanomaterials, 2020. doi: 10.1155/2020/6014816.
63. Ye X, Zhang Y, Liu T, et al. Beta-tricalcium phosphate enhanced mechanical and biological properties of 3D-printed polyhydroxyalkanoates scaffold for bone tissue engineering. Int J Biol Macromol, 2022, 209(Pt A): 1553-1561.
64. Yang S, Wang J, Tang L, et al. Mesoporous bioactive glass doped-poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) composite scaffolds with 3-dimensionally hierarchical pore networks for bone regeneration. Colloids Surf B Biointerfaces, 2014, 116: 72-80.
65. Zhao S, Zhu M, Zhang J, et al. Three dimensionally printed mesoporous bioactive glass and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) composite scaffolds for bone regeneration. J Mater Chem B, 2014, 2(36): 6106-6118.
66. Boeree NR, Dove J, Cooper JJ, et al. Development of a degradable composite for orthopaedic use: mechanical evaluation of an hydroxyapatite-polyhydroxybutyrate composite material. Biomaterials, 1993, 14(10): 793-796.
67. Czechowska J, Skibiński S, Guzik M, et al. Silver decorated βTCP-poly (3hydroxybutyrate) scaffolds for bone tissue engineering. Materials (Basel), 2021, 14(15): 4227. doi: 10.3390/ma14154227.
68. Yuan S, Shen Y, Li Z. Injectable cell- and growth factor-free poly(4-hydroxybutyrate) (P4HB) microspheres with open porous structures and great efficiency of promoting bone regeneration. ACS Appl Bio Mater, 2021, 4(5): 4432-4440.
69. Chotchindakun K, Pekkoh J, Ruangsuriya J, et al. Fabrication and characterization of cinnamaldehyde-loaded mesoporous bioactive glass nanoparticles/PHBV-based microspheres for preventing bacterial infection and promoting bone tissue regeneration. Polymers (Basel), 2021, 13(11): 1794. doi: 10.3390/polym13111794.
70. Zhao XH, Peng XL, Gong HL, et al. Osteogenic differentiation system based on biopolymer nanoparticles for stem cells in simulated microgravity. Biomed Mater, 2021, 16(4): 044102. doi: 10.1088/1748-605X/abe9d1.
71. Almeida Neto GR, Barcelos MV, Ribeiro MEA, et al. Formulation and characterization of a novel PHBV nanocomposite for bone defect filling and infection treatment. Mater Sci Eng C Mater Biol Appl, 2019, 104: 110004. doi: 10.1016/j.msec.2019.110004.
72. Li XT, Zhang Y, Chen GQ. Nanofibrous polyhydroxyalkanoate matrices as cell growth supporting materials. Biomaterials, 2008, 29(27): 3720-3728.
73. Kong I, Tshai K, Hoque ME. Manufacturing of natural fibre-reinforced polymer composites by solvent casting method//Salit M, Jawaid M, Yusoff N, et al. Manufacturing of natural fibre reinforced polymer composites. Cham: Springer, 2015: 331-349.
74. Hou Q, Grijpma DW, Feijen J. Porous polymeric structures for tissue engineering prepared by a coagulation, compression moulding and salt leaching technique. Biomaterials, 2003, 24(11): 1937-1947.
75. Sodian R, Hoerstrup SP, Sperling JS, et al. Evaluation of biodegradable, three-dimensional matrices for tissue engineering of heart valves. ASAIO J, 2000, 46(1): 107-110.
76. Wang YW, Wu Q, Chen GQ. Attachment, proliferation and differentiation of osteoblasts on random biopolyester poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) scaffolds. Biomaterials, 2004, 25(4): 669-675.
77. Sodian R, Hoerstrup SP, Sperling JS, et al. Early in vivo experience with tissue-engineered trileaflet heart valves. Circulation, 2000, 102(19 Suppl 3): 22-29.
78. Wei DX, Dao JW, Liu HW, et al. Suspended polyhydroxyalkanoate microspheres as 3D carriers for mammalian cell growth. Artif Cells Nanomed Biotechnol, 2018, 46(sup2): 473-483.
79. 魏岱旭, 李腾, 张浩千, 等. 一种窄粒度分布的聚羟基脂肪酸酯微球及其制备方法: 中国, CN113617305B [P/OL]. 2021-11-09.
80. CHOINIERE P. Development of polyhydroxyalkanoate nanoparticles for cancer therapy[OL]. [2023-02-03] https://www.semanticscholar.org/paper/Development-of-Polyhydroxyalkanoate-Nanoparticles-Choiniere/5f1ce1cd80a37a5552db0dc80888f98bdce077c4#citing-papers.
81. Samrot AV, Samanvitha SK, Shobana N, et al. The synthesis, characterization and applications of polyhydroxyalkanoates (PHAs) and PHA-based nanoparticles. Polymers (Basel), 2021, 13(19): 3302.
82. Peprah BA, Ramsay JA, Ramsay BA. Dense stable suspensions of medium-chain-length poly (3-hydroxyalkanoate) nanoparticles. European Polymer Journal, 2016, 84: 137-146.
83. Deepak V, Pandian Sb, Kalishwaralal K, et al. Purification, immobilization, and characterization of nattokinase on PHB nanoparticles. Bioresour Technol, 2009, 100(24): 6644-6646.
84. Vilos C, Morales FA, Solar PA, et al. Paclitaxel-PHBV nanoparticles and their toxicity to endometrial and primary ovarian cancer cells. Biomaterials, 2013, 34(16): 4098-4108.
85. Kılıçay E, Demirbilek M, Türk M, et al. Preparation and characterization of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHX) based nanoparticles for targeted cancer therapy. Eur J Pharm Sci, 2011, 44(3): 310-320.
86. Gossmann R, Langer K, Mulac D. New perspective in the formulation and characterization of didodecyldimethylammonium bromide (DMAB) stabilized poly(lactic-co-glycolic acid) (PLGA) nanoparticles. PLoS One, 2015, 10(7): e0127532. doi: 10.1371/journal.pone.0127532.
87. Lu XY, Ciraolo E, Stefenia R, et al. Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines. Appl Microbiol Biotechnol, 2011, 89(5): 1423-1433.
88. Knowles JC. Development of a natural degradable polymer for orthopaedic use. J Med Eng Technol, 1993, 17(4): 129-137.
89. Doyle C, Tanner ET, Bonfield W. In vitro and in vivo evaluation of polyhydroxybutyrate and of polyhydroxybutyrate reinforced with hydroxyapatite. Biomaterials, 1991, 12(9): 841-847.
90. Luklinska ZB, Bonfield W. Morphology and ultrastructure of the interface between hydroxyapatite-polyhydroxybutyrate composite implant and bone. J Mater Sci Mater Med, 1997, 8(6): 379-383.
91. Bernd HE, Kunze C, Freier T, et al. Poly (3-hydroxybutyrate) (PHB) patches for covering anterior skull base defects-an animal study with minipigs. Acta Otolaryngol, 2009, 129(9): 1010-1017.
92. Köse GT, Ber S, Korkusuz F, et al. Poly (3-hydroxybutyric acid-co-3-hydroxyvaleric acid) based tissue engineering matrices. J Mater Sci Mater Med, 2003, 14(2): 121-126.
93. Wang YW, Wu Q, Chen J, et al. Evaluation of three-dimensional scaffolds made of blends of hydroxyapatite and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) for bone reconstruction. Biomaterials, 2005, 26(8): 899-904.
94. Wang Y, Gao R, Wang PP, et al. The differential effects of aligned electrospun PHBHHx fibers on adipogenic and osteogenic potential of MSCs through the regulation of PPARγ signaling. Biomaterials, 2012, 33(2): 485-493.
95. Wang Y, Jiang XL, Yang SC, et al. MicroRNAs in the regulation of interfacial behaviors of MSCs cultured on microgrooved surface pattern. Biomaterials, 2011, 32(35): 9207-9217.
96. Wei X, Hu YJ, Xie WP, et al. Influence of poly (3-hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyhexanoate) on growth and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. J Biomed Mater Res A, 2009, 90(3): 894-905.
97. Shishatskaya EI, Khlusov IA, Volova TG. A hybrid PHB-hydroxyapatite composite for biomedical application: production, in vitro and in vivo investigation. J Biomater Sci Polym Ed, 2006, 17(5): 481-498.
98. Degli Esposti M, Chiellini F, Bondioli F, et al. Highly porous PHB-based bioactive scaffolds for bone tissue engineering by in situ synthesis of hydroxyapatite. Mater Sci Eng C Mater Biol Appl, 2019, 100: 286-296.
99. Sadat-Shojai M, Khorasani MT, Jamshidi A. A new strategy for fabrication of bone scaffolds using electrospun nano-HAp/PHB fibers and protein hydrogels. Chemical Engineering Journal, 2016, 289: 38-47.
100. Yu J, Xu N, Xi Y, et al. Adhesion behavior of escherichia coli on plasma-sprayed Zn and Ag co-incorporated calcium silicate coatings with varying surface roughness. Journal of Thermal Spray Technology, 2018, 27(8): 1428-1435.
101. Fan L, Xie J, Zheng Y, et al. Antibacterial, Self-adhesive, recyclable, and tough conductive composite hydrogels for ultrasensitive strain sensing. ACS Appl Mater Interfaces, 2020, 12(19): 22225-22236.
102. Fan L, Hu L, Xie J, et al. Biosafe, self-adhesive, recyclable, tough, and conductive hydrogels for multifunctional sensors. Biomater Sci, 2021, 9(17): 5884-5896.
103. Fan L, He Z, Peng X, et al. Injectable, intrinsically antibacterial conductive hydrogels with self-healing and pH stimulus responsiveness for epidermal sensors and wound healing. ACS Appl Mater Interfaces, 2021, 13(45): 53541-53552.
104. Wei DX, Zhang XW. Biosynthesis, bioactivity, biosafety and applications of antimicrobial peptides for human health. Biosafety and Health, 2022. doi: 10.1016/j.bsheal.2022.02.003.
105. 魏岱旭, 龚海伦, 张旭维. 抗菌肽的生物合成及医学应用. 合成生物学, 2022, 3(4): 709-727.
106. Ding YW, Zhang XW, Mi CH, et al. Recent advances in hyaluronic acid-based hydrogels for 3D bioprinting in tissue engineering applications. Smart Materials in Medicine, 2023, 4: 59-68.
107. Ding YW, Wang ZY, Ren ZW, et al. Advances in modified hyaluronic acid-based hydrogels for skin wound healing. Biomater Sci, 2022, 10(13): 3393-3409.

Previous Article
Regulation of non-coding RNA in type H vessels angiogenesis of bone
Next Article
Injectable hydrogel microspheres experimental research for the treatment of osteoarthritis

Chinese Journal of Reparative and Reconstructive Surgery

Research progress on medical devices of polyhydroxyalkanoate in orthopedics

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content