医用聚羟基脂肪酸酯（PHA）的生物合成策略及其在人类健康领域的新进展

田英入; 黄晓云; 刀金威; 李玥昊; 徐涛; 杨辉; 万丹丹; 魏岱旭

doi:10.12211/2096-8280.2025-059

您当前的位置：

首页 >

文章列表页 >

医用聚羟基脂肪酸酯（PHA）的生物合成策略及其在人类健康领域的新进展

特约评述 | 更新时间：2026-01-15

- 医用聚羟基脂肪酸酯（PHA）的生物合成策略及其在人类健康领域的新进展
- Biosynthetic strategies of medical polyhydroxyalkanoate （PHA） and their new developments for human health
- 合成生物学 2025年6卷第6期页码：1332-1348
- 作者机构：
  
  1.曲靖健康医学院，云南曲靖 655100
  2.德宏师范学院德宏生物医药工程研究中心，云南德宏 678400
  3.成都大学临床医学院与附属医院，四川成都 610106
- 作者简介：
  
  [ "田英入（1996—），女，硕士研究生。研究方向为生物材料、合成生物学、组织工程与再生医学、生殖医学、妇产科学、生理学。 E-mail：tianyinrude@163.com" ]
  [ "黄晓云（1982—），女，副教授。研究方向为小细胞肺癌（NSCLC）的发病机制、治疗药物和智能给药系统等，目标是识别疾病中的关键分子和通路机制，以开发可行的治疗目标和方法用于临床应用。 E-mail：953614419@qq.com" ]
  [ "刀金威（1986—），男，博士，副教授。研究方向为生物材料学、医学组织工程学和病原生物学。 E-mail：daojw15@tsinghua.org.cn" ]
  [ "魏岱旭（1986—），男，博士，教授，博士生导师。主要研究方向为聚羟基脂肪酸酯（PHA）及其酮体衍生物（3HB）的生物学效应及综合利用。曾带领本科生获得2019年和2021年iGEM金奖。 E-mail：weidaixu@cdu.edu.cn" ]
- 基金信息：
  
  四川省卫生健康委员会医学科学研究项目(24WSXT106);中国陕西省自然科学基础研究计划(2024JC-YBMS-706);自贡市重点科技计划［自贡市中西医结合研究院协同创新类(2025ZXY0101);自贡市医学大数据与人工智能研究院协同创新类(2023-YGY-1-02);自贡市脑科学院协同创新类(2024-NKY-01-01;2022ZCNKY07);云南省科学技术厅－云南中医药大学基础研究联合基金(202101AZ070001-102);云南省教育厅科学研究基金(2023J1773);云南省科技厅科技计划(202401AZ070001-097);曲靖健康医学院校级科学研究基金(2025ZD04)
- DOI：10.12211/2096-8280.2025-059
  中图分类号： TQ323.4;Q503;R318.08;R329;X171.5
- 收稿：2025-06-12，
  
  修回：2025-11-04，
  
  纸质出版：2025-12-31
- 稿件说明：
移动端阅览
田英入，黄晓云，刀金威，李玥昊，徐涛，杨辉，万丹丹，魏岱旭. 医用聚羟基脂肪酸酯（PHA）的生物合成策略及其在人类健康领域的新进展［J］. 合成生物学， 2025， 6（6）： 1332-1348

TIAN Yingru， HUANG Xiaoyun， DAO Jinwei， LI Yuehao， XU Tao， YANG Hui， WAN Dandan， WEI Daixu. Biosynthetic strategies of medical polyhydroxyalkanoate （PHA） and their new developments for human health［J］. Synthetic Biology Journal， 2025， 6（6）： 1332-1348
田英入，黄晓云，刀金威，李玥昊，徐涛，杨辉，万丹丹，魏岱旭. 医用聚羟基脂肪酸酯（PHA）的生物合成策略及其在人类健康领域的新进展［J］. 合成生物学， 2025， 6（6）： 1332-1348 DOI： 10.12211/2096-8280.2025-059.

TIAN Yingru， HUANG Xiaoyun， DAO Jinwei， LI Yuehao， XU Tao， YANG Hui， WAN Dandan， WEI Daixu. Biosynthetic strategies of medical polyhydroxyalkanoate （PHA） and their new developments for human health［J］. Synthetic Biology Journal， 2025， 6（6）： 1332-1348 DOI： 10.12211/2096-8280.2025-059.

摘要

聚羟基脂肪酸酯（PHA）是一类具有生物相容性、生物可降解性以及优良材料学性能的生物合成聚酯，在医药领域展现出巨大的应用潜力。然而，产能低限制了PHA的应用。近年来，合成生物技术的发展为PHA的优化生产提供了新途径。本文综述了PHA作为医用材料的优势，包括单体多样性、可控降解性及优异的生物相容性；探讨了合成生物技术在PHA生产中的应用，如CRISPR/Cas工具、启动子工程、RBS优化、微生物细胞形态工程、染色体整合技术等策略，这些策略可优化合成途径和提高产量，并且推动工业化制备医用级PHA的进展。并进一步阐述了医用级PHA近些年在骨修复、皮肤再生、心血管工程等领域取得的显著应用成果。未来，融合多学科创新有望突破PHA的技术壁垒，使其成为生物医用材料领域的核心选项，推动再生医学的发展。

Abstract

Polyhydroxyalkanoates (PHAs) represent a versatile class of microbial polyesters with exceptional biocompatibility

tunable biodegradability

and a broad range of mechanical and chemical properties. These characteristics make PHA highly suitable for diverse biomedical applications

including tissue engineering scaffolds

targeted drug delivery systems

wound dressings

and implantable devices. Notably

PHA degradation products such as 3-hydroxybutyrate are endogenous metabolites

which minimizes immunogenic responses and enhances long-term biocompatibility compared to conventional synthetic polymers. Recent advances in synthetic biology have significantly improved PHA biosynthesis. Metabolic engineering strategies

including CRISPR/Cas9-mediated genome editing for redirecting carbon flux toward PHA accumulation

CRISPR interference for modulating competing pathways

and optimization of promoter and ribosome-binding site (RBS) libraries

have enabled precise control over monomer composition and polymer properties. Additionally

microbial morphological engineering such as FtsZ-targeted cell elongation has been used to increase intracellular PHA content to over 90% of cellular dry weight. These developments have facilitated the synthesis of tailored PHA variants

ranging from rigid poly(3-hydroxybutyrate) (PHB) to elastomeric poly(3-hydroxybutyrate-

-4-hydroxybutyrate) (P34HB). Medical-grade PHA has shown significant translational potential across multi

ple therapeutic domains. Injectable porous microspheres composed of poly(3-hydroxybutyrate-

-3-hydroxyvalerate-

-3-hydroxyhexanoate) (PBVHx) have been developed for minimally invasive bone regeneration. Electrospun P34HB scaffolds exhibit simultaneous antibacterial and pro-angiogenic activities

accelerating wound healing. PHA-based nanocarriers enable sustained drug release for Alzheimer's disease and systemic lupus erythematosus treatment. Furthermore

virus-mimetic PHA particles have been exploited as adjuvant systems to enhance antigen presentation in tuberculosis and COVID-19 vaccine platforms. Future perspectives highlight the convergence of synthetic biology

materials science

and clinical translation to fully realize PHA’s biomedical potential. Next-generation industrial biotechnology (NGIB)

which uses halophilic microorganisms for continuous fermentation under open conditions combined with advanced downstream purification protocols

is expected to improve the scalability and accessibility of medical-grade PHA. Integration with emerging technologies such as 3D bioprinting and organoid culture systems will expand PHA’s utility in complex

patient-specific tissue engineering applications. Collectively

these advances establish PHA as a highly promising foundational biomaterial platform for next-generation regenerative medicine and targeted therapeutic strategies.

关键词

Keywords

references

ZHANG S Q , YUAN H Z , MA X , et al . Carbon cycle of polyhydroxyalkanoates (CCP): biosynthesis and biodegradation [J ] . Environmental Research , 2025 , 269 : 120904 .

REN Z W , WANG Z Y , DING Y W , et al . Polyhydroxyalkanoates: the natural biopolyester for future medical innovations [J ] . Biomaterials Science , 2023 , 11 ( 18 ): 6013 - 6034 .

MI C H , QI X Y , DING Y W , et al . Recent advances of medical polyhydroxyalkanoates in musculoskeletal system [J ] . Biomaterials Translational , 2023 , 4 ( 4 ): 234 - 247 .

MI C H , QI X Y , ZHOU Y W , et al . Advances in medical polyesters for vascular tissue engineering [J ] . Discover Nano , 2024 , 19 ( 1 ): 125 .

LI H R , ZHOU J , ZHOU Y W , et al . Advances in photocrosslinked natural hydrogel-based microspheres for bone repair [J ] . Journal of Polymer Science , 2024 , 62 ( 22 ): 4966 - 4992 .

HUANG X Y , QI Z D , DAO J W , et al . Current situation and challenges of polyhydroxyalkanoates-derived nanocarriers for cancer therapy [J ] . Smart Materials in Medicine , 2024 , 5 ( 4 ): 529 - 541 .

WEI D X , CHEN Z C . Current situation and challenge of exogenous 3-hydroxybutyrate derived from polyhydroxyalkanoates for elderly health: a review [J ] . International Journal of Biological Macromolecules , 2025 , 285 : 138328 .

XIANG Y , WANG Q Q , LAN X Q , et al . Function and treatment strategies of β-hydroxybutyrate in aging [J ] . Smart Materials in Medicine , 2023 , 4 : 160 - 172 .

WANG B L , WU J F , XIAO D , et al . 3-Hydroxybutyrate in the brain: biosynthesis, function, and disease therapy [J ] . Brain‐X , 2023 , 1 ( 1 ): e6 .

LIU S , YU J M , GAN Y C , et al . Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications [J ] . Military Medical Research , 2023 , 10 ( 1 ): 16 .

XU T , HUANG X Y , DAO J W , et al . Synthetic biology for medical biomaterials [J ] . Interdisciplinary Medicine , 2025 , 3 ( 4 ): e20240087 .

ZHAO X H , PENG X L , GONG H L , et al . Osteogenic differentiation system based on biopolymer nanoparticles for stem cells in simulated microgravity [J ] . Biomedical Materials , 2021 , 16 ( 4 ): 044102 .

ZHAO X H , NIU Y N , MI C H , et al . Electrospinning nanofibers of microbial polyhydroxyalkanoates for applications in medical tissue engineering [J ] . Journal of Polymer Science , 2021 , 59 ( 18 ): 1994 - 2013 .

PENG X L , CHENG J S Y , GONG H L , et al . Advances in the design and development of SARS-CoV-2 vaccines [J ] . Military Medical Research , 2021 , 8 ( 1 ): 67 .

FU S Y , DU X Y , ZHU M , et al . 3D printing of layered mesoporous bioactive glass/sodium alginate-sodium alginate scaffolds with controllable dual-drug release behaviors [J ] . Biomedical Materials , 2019 , 14 ( 6 ): 065011 .

DU X Y , WEI D X , HUANG L , et al . 3D printing of mesoporous bioactive glass/silk fibroin composite scaffolds for bone tissue engineering [J ] . Materials Science & Engineering C , Materials for Biological Applications, 2019 , 103 : 109731 .

CHE X M , WEI D X , CHEN G Q . Superhydrophobic polyhydroxyalkanoates: preparation and applications [J ] . Biomacromolecules , 2019 , 20 ( 2 ): 618 - 624 .

WEI D X , DAO J W , CHEN G Q . A micro-ark for cells: highly open porous polyhydroxyalkanoate microspheres as injectable scaffolds for tissue regeneration [J ] . Advanced Materials , 2018 , 30 ( 31 ): 1802273 .

QIN Q , LING C , ZHAO Y Q , et al . CRISPR/Cas9 editing genome of extremophile Halomonas spp [J ] . Metabolic Engineering , 2018 , 47 : 219 - 229 .

JUNG H R , YANG S Y , MOON Y M , et al . Construction of efficient platform Escherichia coli strains for polyhydroxyalkanoate production by engineering branched pathway [J ] . Polymers , 2019 , 11 ( 3 ): 509 .

TAO W , LV L , CHEN G Q . Engineering Halomonas species TD01 for enhanced polyhydroxyalkanoates synthesis via CRISPRi [J ] . Microbial Cell Factories , 2017 , 16 ( 1 ): 48 .

LV L , REN Y L , CHEN J C , et al . Application of CRISPRi for prokaryotic metabolic engineering involving multiple genes, a case study: controllable P(3HB-co-4HB) biosynthesis [J ] . Metabolic Engineering , 2015 , 29 : 160 - 168 .

WANG X P , LIN L , DONG J D , et al . Simultaneous improvements of Pseudomonas cell growth and polyhydroxyalkanoate production from a lignin derivative for lignin-consolidated bioprocessing [J ] . Applied and Environmental Microbiology , 2018 , 84 ( 18 ): e01469-18 .

RIGOUIN C , LAJUS S , OCANDO C , et al . Production and characterization of two medium-chain-length polydroxyalkano ates by engineered strains of Yarrowia lipolytica [J ] . Microbial Cell Factories , 2019 , 18 ( 1 ): 99 .

ZHANG X , LIN Y N , WU Q , et al . Synthetic biology and genome-editing tools for improving PHA metabolic engineering [J ] . Trends in Biotechnology , 2020 , 38 ( 7 ): 689 - 700 .

LIU C L , WANG X T , YANG H Y , et al . Biodegradable polyhydroxyalkanoates production from wheat straw by recombinant Halomonas elongata A1 [J ] . International Journal of Biological Macromolecules , 2021 , 187 : 675 - 682 .

SHEN R , YIN J , YE J W , et al . Promoter engineering for enhanced P(3HB- co -4HB) production by Halomonas bluephagenesis [J ] . ACS Synthetic Biology , 2018 , 7 ( 8 ): 1897 - 1906 .

KIM E J , KIM K J . Crystal structure and biochemical characterization of PhaA from Ralstonia eutropha , a polyhydroxyalkanoate-producing bacterium [J ] . Biochemical and Biophysical Research Communications , 2014 , 452 ( 1 ): 124 - 129 .

KIM E J , SON H F , KIM S , et al . Crystal structure and biochemical characterization of beta-keto thiolase B from polyhydroxyalkanoate-producing bacterium Ralstonia eutropha H16 [J ] . Biochemical and Biophysical Research Communications , 2014 , 444 ( 3 ): 365 - 369 .

KIM J , CHANG J H , KIM E J , et al . Crystal structure of ( R )-3-hydroxybutyryl-CoA dehydrogenase PhaB from Ralstonia eutropha [J ] . Biochemical and Biophysical Research Communications , 2014 , 443 ( 3 ): 783 - 788 .

WITTENBORN E C , JOST M , WEI Y F , et al . Structure of the catalytic domain of the classⅠpolyhydroxybutyrate synthase from Cupriavidus necator [J ] . Journal of Biological Chemistry , 2016 , 291 ( 48 ): 25264 - 25277 .

YE J W , HU D K , YIN J , et al . Stimulus response-based fine-tuning of polyhydroxyalkanoate pathway in Halomonas [J ] . Metabolic Engineering , 2020 , 57 : 85 - 95 .

ZHENG S , ZHANG Z H , JIANG P , et al . A self-stimulating system based on a polyhydroxyalkanoates coupled induction mechanism and its applications for Halomonas [J ] . Chemical Engineering Journal , 2024 , 489 : 151413 .

WANG X , HAN J N , ZHANG X , et al . Reversible thermal regulation for bifunctional dynamic control of gene expression in Escherichia coli [J ] . Nature Communications , 2021 , 12 : 1411 .

REN K , ZHAO Y Q , CHEN G Q , et al . Construction of a stable expression system based on the endogenous hbpB / hbpC toxin-antitoxin system of Halomonas bluephagenesis [J ] . ACS Synthetic Biology , 2024 , 13 ( 1 ): 61 - 67 .

MA Y Y , YE J W , LIN Y N , et al . Flux optimization using multiple promoters in Halomonas bluephagenesis as a model chassis of the next generation industrial biotechnology [J ] . Metabolic Engineering , 2024 , 81 : 249 - 261 .

LI Z J , SHI Z Y , JIAN J , et al . Production of poly(3-hydroxybutyrate- co -4-hydroxybutyrate) from unrelated carbon sources by metabolically engineered Escherichia coli [J ] . Metabolic Engineering , 2010 , 12 ( 4 ): 352 - 359 .

FU X Z , TAN D , AIBAIDULA G , et al . Development of Halomonas TD01 as a host for open production of chemicals [J ] . Metabolic Engineering , 2014 , 23 : 78 - 91 .

CHEN G Q , JIANG X R . Next generation industrial biotechnology based on extremophilic bacteria [J ] . Current Opinion in Biotechnology , 2018 , 50 : 94 - 100 .

DYE N A , PINCUS Z , FISHER I C , et al . Mutations in the nucleotide binding pocket of MreB can alter cell curvature and polar morphology in Caulobacter [J ] . Molecular Microbiology , 2011 , 81 ( 2 ): 368 - 394 .

JIANG X R , YAO Z H , CHEN G Q . Controlling cell volume for efficient PHB production by Halomonas [J ] . Metabolic Engineering , 2017 , 44 : 30 - 37 .

WU H , FAN Z Y , JIANG X R , et al . Enhanced production of polyhydroxybutyrate by multiple dividing E . coli [J ] . Microbial Cell Factories , 2016 , 15 ( 1 ): 128 .

WU H , CHEN J C , CHEN G Q . Engineering the growth pattern and cell morphology for enhanced PHB production by Escherichia coli [J ] . Applied Microbiology and Biotechnology , 2016 , 100 ( 23 ): 9907 - 9916 .

YIN J , CHEN J C , WU Q , et al . Halophiles, coming stars for industrial biotechnology [J ] . Biotechnology Advances , 2015 , 33 ( 7 ): 1433 - 1442 .

PAULDINE J R . Assessment of Purification methods for the removal of endotoxins from polymers generated by E . coli[D ] . Syracuse : State University of New York College of Environmental Science and Forestry , 2016 .

RAN G Q , TAN D , ZHAO J P , et al . Functionalized polyhydroxyalkanoate nano-beads as a stable biocatalyst for cost-effective production of the rare sugar D-allulose [J ] . Bioresource Technology , 2019 , 289 : 121673 .

CHEN X B , YU L P , QIAO G Q , et al . Reprogramming Halomonas for industrial production of chemicals [J ] . Journal of Industrial Microbiology & Biotechnology , 2018 , 45 ( 7 ): 545 - 554 .

CHEN G Q , HAJNAL I , WU H , et al . Engineering biosynthesis mechanisms for diversifying polyhydroxyalkanoates [J ] . Trends in Biotechnology , 2015 , 33 ( 10 ): 565 - 574 .

XU N , WEI L , LIU J . Recent advances in the applications of promoter engineering for the optimization of metabolite biosynthesis [J ] . World Journal of Microbiology and Biotechnology , 2019 , 35 ( 2 ): 33 .

LI T , YE J W , SHEN R , et al . Semirational approach for ultrahigh poly(3-hydroxybutyrate) accumulation in Escherichia coli by combining one-step library construction and high-throughput screening [J ] . ACS Synthetic Biology , 2016 , 5 ( 11 ): 1308 - 1317 .

SALIS H M , MIRSKY E A , VOIGT C A . Automated design of synthetic ribosome binding sites to control protein expression [J ] . Nature Biotechnology , 2009 , 27 ( 10 ): 946 - 950 .

ALI RAZA Z , ABID S , BANAT I M . Polyhydroxyalkanoates: characteristics, production, recent developments and applications [J ] . International Biodeterioration & Biodegradation , 2018 , 126 : 45 - 56 .

STEINBÜCHEL A , LÜTKE-EVERSLOH T . Metabolic engineering and pathway construction for biotechnological production of relevant polyhydroxyalkanoates in microorganisms [J ] . Biochemical Engineering Journal , 2003 , 16 ( 2 ): 81 - 96 .

WANG Z Y , QIN Q , ZHENG Y F , et al . Engineering the permeability of Halomonas bluephagenesis enhanced its chassis properties [J ] . Metabolic Engineering , 2021 , 67 : 53 - 66 .

TAN D , WU Q , CHEN J C , et al . Engineering Halomonas TD01 for the low-cost production of polyhydroxyalkanoates [J ] . Metabolic Engineering , 2014 , 26 : 34 - 47 .

WANG Y , WU H , JIANG X R , et al . Engineering Escherichia coli for enhanced production of poly(3-hydroxybutyrate- co -4-hydroxybutyrate) in larger cellular space [J ] . Metabolic Engineering , 2014 , 25 : 183 - 193 .

YUAN S S , SHEN Y , LI Z B . Injectable cell- and growth factor-free poly(4-hydroxybutyrate) (P4HB) microspheres with open porous structures and great efficiency of promoting bone regeneration [J ] . ACS Applied Bio Materials , 2021 , 4 ( 5 ): 4432 - 4440 .

RAHMAN M , PENG X L , ZHAO X H , et al . 3D bioactive cell-free-scaffolds for in-vitro / in-vivo capture and directed osteoinduction of stem cells for bone tissue regeneration [J ] . Bioactive Materials , 2021 , 6 ( 11 ): 4083 - 4095 .

HUANG X Y , ZHOU X X , YANG H , et al . Directed osteogenic differentiation of human bone marrow mesenchymal stem cells via sustained release of BMP4 from PBVHx-based nanoparticles [J ] . International Journal of Biological Macromolecules , 2024 , 265 ( Pt 1 ): 130649 .

REYHANEH GHAVAMI L , BIAZAR E , TALEGHANI A S , et al . Design of curcumin-loaded electrospun polyhydroxybutyrate mat as a wound healing material [J ] . Nano Biomedicine and Engineering , 2020 , 12 ( 1 ): 14 - 20 .

LI J , CHEN J N , PENG Z X , et al . Multifunctional electrospinning polyhydroxyalkanoate fibrous scaffolds with antibacterial and angiogenesis effects for accelerating wound healing [J ] . ACS Applied Materials & Interfaces , 2023 , 15 ( 1 ): 364 - 377 .

DING Y W , LI Y , ZHANG Z W , et al . Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment [J ] . Bioactive Materials , 2024 , 38 : 95 - 108 .

GAO J , HUANG Z Z , GUO H W , et al . Effect of wall structures on mechanical properties of small caliber PHBHHx vascular grafts [J ] . Fibers and Polymers , 2019 , 20 ( 11 ): 2261 - 2267 .

JIAN Y H , ZHU Y F . Poly 3-hydroxybutyrate 4-hydroxybutyrate (P34HB) as a potential polymer for drug-eluting coatings on metal coronary stents [J ] . Polymers , 2022 , 14 ( 5 ): 994 .

ANTONOVA L V , SEVOSTYANOVA V V , MIRONOV A V , et al . In situ vascular tissue remodeling using biodegradable tubular scaffolds with incorporated growth factors and chemoattractant molecules [J ] . Complex Issues of Cardiovascular Diseases , 2018 , 7 ( 2 ): 25 - 36 .

WANG D F , WANG C , BI Z J , et al . Expanded polytetrafluoroethylene/poly(3-hydroxybutyrate) (ePTFE/PHB) triboelectric nanogenerators and their potential applications as self-powered and sensing vascular grafts [J ] . Chemical Engineering Journal , 2023 , 455 : 140494 .

CHEN F F , LIU X Y , GE X Y , et al . Porous polydroxyalkanoates (PHA) scaffolds with antibacterial property for oral soft tissue regeneration [J ] . Chemical Engineering Journal , 2023 , 451 : 138899 .

PHUEGYOD S , PRAMUAL S , WATTANAVICHEAN N , et al . Microbial poly(hydroxybutyrate- co -hydroxyvalerate) scaffold for periodontal tissue engineering [J ] . Polymers , 2023 , 15 ( 4 ): 855 .

HU J , WANG M , XIAO X Y , et al . A novel long-acting azathioprine polyhydroxyalkanoate nanoparticle enhances treatment efficacy for systemic lupus erythematosus with reduced side effects [J ] . Nanoscale , 2020 , 12 ( 19 ): 10799 - 10808 .

PARLANE N A , WEDLOCK D N , BUDDLE B M , et al . Bacterial polyester inclusions engineered to display vaccine candidate antigens for use as a novel class of safe and efficient vaccine delivery agents [J ] . Applied and Environmental Microbiology , 2009 , 75 ( 24 ): 7739 - 7744 .

WEI D X , CAI D F , TAN Y G , et al . Poly(3-hydroxybutyrate- co -3-hydroxyvalerate -co -3-hydroxyhexanoate)-based microspheres as a sustained platform for Huperzine A delivery for Alzheimer’s disease therapy [J ] . International Journal of Biological Macromolecules , 2024 , 282 ( Pt 1 ): 136582 .

MARINO G , ROSSO F , CAFIERO G , et al . Beta-tricalcium phosphate 3D scaffold promote alone osteogenic differentiation of human adipose stem cells: in vitro study [J ] . Journal of Materials Science Materials in Medicine , 2010 , 21 ( 1 ): 353 - 363 .

IM G I , KIM H J , LEE J H . Chondrogenesis of adipose stem cells in a porous PLGA scaffold impregnated with plasmid DNA containing SOX trio ( SOX -5, -6 and -9) genes [J ] . Biomaterials , 2011 , 32 ( 19 ): 4385 - 4392 .

WEI D X , DAO J W , LIU H W , et al . Suspended polyhydroxyalkanoate microspheres as 3D carriers for mammalian cell growth [J ] . Artificial Cells, Nanomedicine, and Biotechnology , 2018 , 46 ( sup2 ): 473 - 483 .

FU N , MENG Z S , JIAO T J , et al . P34HB electrospun fibres promote bone regeneration in vivo [J ] . Cell Proliferation , 2019 , 52 ( 3 ): e12601 .

MEISCHEL M , EICHLER J , MARTINELLI E , et al . Adhesive strength of bone-implant interfaces and in-vivo degradation of PHB composites for load-bearing applications [J ] . Journal of the Mechanical Behavior of Biomedical Materials , 2016 , 53 : 104 - 118 .

BERND H E , KUNZE C , FREIER T , et al . Poly(3-hydroxybutyrate) (PHB) patches for covering anterior skull base defects - an animal study with minipigs [J ] . Acta Oto-Laryngologica , 2009 , 129 ( 9 ): 1010 - 1017 .

ZHANG X , LI J , CHEN J , et al . Enhanced bone regeneration via PHA scaffolds coated with polydopamine-captured BMP2 [J ] . Journal of Materials Chemistry B , 2022 , 10 ( 32 ): 6214 - 6227 .

ZHANG H N , MIGNECO F , LIN C Y , et al . Chemically-conjugated bone morphogenetic protein-2 on three-dimensional polycaprolactone scaffolds stimulates osteogenic activity in bone marrow stromal cells [J ] . Tissue Engineering Part A , 2010 , 16 ( 11 ): 3441 - 3448 .

BARBOSA J L , DE MELO M I A , DA SILVA CUNHA P , et al . Development of a membrane and a bilayer of chitosan, gelatin, and polyhydroxybutyrate to be used as wound dressing for the regeneration of rat excisional wounds [J ] . Journal of Biomedical Materials Research Part A , 2024 , 112 ( 1 ): 82 - 98 .

DAISY E R A C , RAJENDRAN N K , HOURELD N N , et al . Curcumin and Gymnema sylvestre extract loaded graphene oxide-polyhydroxybutyrate-sodium alginate composite for diabetic wound regeneration [J ] . Reactive and Functional Polymers , 2020 , 154 : 104671 .

SANHUEZA C , HERMOSILLA J , BUGALLO-CASAL A , et al . One-step electrospun scaffold of dual-sized gelatin/poly-3-hydroxybutyrate nano/microfibers for skin regeneration in diabetic wound [J ] . Materials Science & Engineering C , Materials for Biological Applic ations, 2021 , 119 : 111602 .

PESCHEL G , DAHSE H M , KONRAD A , et al . Growth of keratinocytes on porous films of poly(3-hydroxybutyrate) and poly(4-hydroxybutyrate) blended with hyaluronic acid and chitosan [J ] . Journal of Biomedical Materials Research Part A , 2008 , 85 A( 4 ): 1072 - 1081 .

RIVERA-BRISO A L , AACHMANN F L , MORENO-MANZANO V , et al . Graphene oxide nanosheets versus carbon nanofibers: enhancement of physical and biological properties of poly(3-hydroxybutyrate- co -3-hydroxyvalerate) films for biomedical applications [J ] . International Journal of Biological Macromolecules , 2020 , 143 : 1000 - 1008 .

JI Y , LI X T , CHEN G Q . Interactions between a poly(3-hydroxybutyrate- co -3-hydroxyvalerate- co -3-hydroxyhexanoate) terpolyester and human keratinocytes [J ] . Biomaterials , 2008 , 29 ( 28 ): 3807 - 3814 .

HE Y , HU Z W , REN M D , et al . Evaluation of PHBHHx and PHBV/PLA fibers used as medical sutures [J ] . Journal of Materials Science: Materials in Medicine , 2014 , 25 ( 2 ): 561 - 571 .

GUO W T , WANG X C , YANG C Y , et al . Microfluidic 3D printing polyhydroxyalkanoates-based bionic skin for wound healing [J ] . Materials Futures , 2022 , 1 ( 1 ): 015401 .

BASNETT P , MATHARU R K , TAYLOR C S , et al . Harnessing polyhydroxyalkanoates and pressurized gyration for hard and soft tissue engineering [J ] . ACS Applied Materials & Interfaces , 2021 , 13 ( 28 ): 32624 - 32639 .

ANTONOVA L V , KRIVKINA E O , SEVOSTIANOVA V V , et al . Tissue-engineered carotid artery interposition grafts demonstrate high primary patency and promote vascular tissue regeneration in the ovine model [J ] . Polymers , 2021 , 13 ( 16 ): 2637 .

ANTONOVA L V , MIRONOV A V , YUZHALIN A E , et al . A brief report on an implantation of small-caliber biodegradable vascular grafts in a carotid artery of the sheep [J ] . Pharmaceuticals , 2020 , 13 ( 5 ): 101 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

抗菌肽的生物合成及医学应用

合成生物学赋能细胞膜纳米颗粒的精准诊疗

合成生物学策略下的人工血液研究进展