Recent advances of medical polyhydroxyalkanoates in musculoskeletal system

doi:10.12336/biomatertransl.2023.04.004

Biomaterials Translational ›› 2023, Vol. 4 ›› Issue (4): 234-247.doi: 10.12336/biomatertransl.2023.04.004

• REVIEW • Previous Articles Next Articles

Recent advances of medical polyhydroxyalkanoates in musculoskeletal system

Chen-Hui Mi^1#, Xin-Ya Qi^1#, Yan-Wen Ding^1#, Jing Zhou¹, Jin-Wei Dao¹^,³, Dai-Xu Wei¹^,²^,⁴^,^*()

1 Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Department of Life Sciences and Medicine, Northwest University, Xi’an, Shaanxi Province, China
2 Zigong Affiliated Hospital of Southwest Medical University, Zigong Psychiatric Research Center, Zigong Institute of Brain Science, Zigong, Sichuan Province, China
3 Dehong Biomedical Engineering Research Center, Dehong Teachers’ College, Dehong, Yunnan Province, China
4 Shaanxi Key Laboratory for Carbon Neutral Technology, Xi’an, Shaanxi Province, China

Received:2023-10-14 Revised:2023-11-03 Accepted:2023-11-29 Online:2023-12-27 Published:2023-12-28
Contact: Dai-Xu Wei, daviddxwei@163.com, or weidaixu@nwu.edu.cn.
About author:#Author equally.

Abstract

Abstract:

Infection and rejection in musculoskeletal trauma often pose challenges for natural healing, prompting the exploration of biomimetic organ and tissue transplantation as a common alternative solution. Polyhydroxyalkanoates (PHAs) are a large family of biopolyesters synthesised in microorganism, demonstrating excellent biocompatibility and controllable biodegradability for tissue remodelling and drug delivery. With different monomer-combination and polymer-types, multi-mechanical properties of PHAs making them have great application prospects in medical devices with stretching, compression, twist in long time, especially in musculoskeletal tissue engineering. This review systematically summarises the applications of PHAs in multiple tissues repair and drug release, encompassing areas such as bone, cartilage, joint, skin, tendons, ligament, cardiovascular tissue, and nervous tissue. It also discusses challenges encountered in their application, including high production costs, potential cytotoxicity, and uncontrollable particle size distribution. In conclusion, PHAs offer a compelling avenue for musculoskeletal system applications, striking a balance between biocompatibility and mechanical performance. However, addressing challenges in their production and application requires further research to unleash their full potential in tackling the complexities of musculoskeletal regeneration.

Key words: drug delivery, musculoskeletal system, polyhydroxyalkanoate, tissue engineering

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Application	Material type	Fabrication method	Function	Reference
Bone	PHB/BC	Salt leaching technique	Promote bone formation in critical size calvarial defects in mice	63
	PHAs/Se-Sr-HA	Solvent casting	A high reduction of the number of Staphylococcus aureus 6538P and Escherichia coli 8739 bacterial cells	36
	PHBV/PLGA	Computer-aided wet-spinning	Support murine preosteoblast cell colonisation and differentiation towards an osteoblastic phenotype	64
	TCP/PHO	Soaking and drying	Enhance the wettability towards more cell-friendly material, enhance the durability of the composites (stress-strain characteristics)	65
	P(3HO-co-3HHX)/HA	Solvent casting‐particulate leaching	Allow migration and proliferation of osteoblasts and mesenchymal cells as well as vascularisation	66
	IM-BM(PLLA+CPC+PHA)	Electrospinning	Reinforce and stabilise incomplete fractures with both mechanical testing and an animal experiment	67
	βTCP/P(3HB)	Polyurethane sponge replica method followed by polymer infiltration	Provide cell-friendly environment, ensure high cell viability, and reduce surface hydrophobicity	68
	PHBV/MBGN/CIN	Emulsion solvent extraction/evaporation	High biological activity and antibacterial performance applied simultaneously in bone tissue engineering	69
Cartilage and joint	Poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate)	Electrospinning	Allow to produce a cartilage repair kit for clinical use to reduce the risk of developing secondary osteoarthritis	70
	PLCL/PHBV	Emulsion solvent evaporation	Enhance the compressive modulus of PLCL scaffolds, but could also serve as scaffolding structures for cartilaginous tissue formation	71
	PHB-CS/HNT	Electrospinning	Demonstrate a significant increase in cell viability of chondrocytes	72
	PHB-starch/HNTs	Electrospinning	Improve the tensile strength, support cell growth and attachment without any toxicity for biomedical applications	73
	PhaP-RGD/PHBHHx	Solvent evaporation	The biomaterial films of PHBHHx modified with PhaP-RGD fusion protein can promote its biocompatibility with chondrocytes	72
			Promote the proliferation and chondrogenic differentiation of human umbilical-cord-derived mesenchymal stem cells seeded on PHBHHx films	74
			Lead to more homogeneous cell spreading, better cell adhesion, proliferation and chondrogenic differentiation in the scaffolds	75
Skin	PHB/PHB-HV	Electrospinning	Improve vascularisation of engineered bone tissue	76
	PHB/CA	Electrospinning	Improve cell proliferation	77
	PHB/HEAA	Grafting	Promote the proliferation of human fibroblasts	78
	P(3HB-co-4HB)	Freeze-drying	Promote the adhesion of mouse fibroblasts	79
	PHB	Electrospinning	Support the growth of normal human dermal fibroblasts and keratinocytes	80
			Promote the healing of diabetic wounds	81, 82
	PHBA/CA	Electrospinning	Improve fibroblast adhesion and growth	83
Tendon and ligament	PHB/PHBV/PHUE/PHOUE	Electrospinning	Promote cell adhesion and proliferation	84
	PHBHHX	Electrospinning	Promote tendon repair in vivo, which is conducive to restoring weight-bearing and motor function	45
		Make thin films	Promote adhesion and migration of mesenchymal stem cells and tendon cells	85
	PHA	Mesh-augmented single-row RCRs and nonaugmented RCRs	Improve the initial biomechanical repair strength of tears at risk of rupture	86
Cardiovascular	PHA	Electrospinning	Promote the fusion of scaffolds with cells	87
	PHB	Electrospinning	Promote the adhesion and growth of cardiomyocytes and cardiac fibroblasts	88
	PHBHHx/SF	Make thin films	Promote cell adhesion and proliferation	89
	P(3HO)	Cardiac patches	Promote the adhesion and proliferation of neonatal ventricular rat muscle cells	90
Nervous	PHB	Electrospinning	Have high biocompatibility with human mesenchymal stem cells	91
			Promotes the adhesion and differentiation of embryonic cells into nerve cells	92
			Support the survival and regeneration of neurons after spinal cord injury	93
	PHB/PHBV	Electrospinning	Promote the interaction between Schwann cells and scaffolds	93
			Triggers the activity of Schwann cells	94
	PCL-PHB	Electrospinning	Pluripotent stem cells were induced to differentiate into neurons	95
	PHBHHx	Porous nerve conduit	Have good nerve regeneration ability, which can promote the rapid functional recovery of damaged nerves	96
		Electrospinning	Promote the differentiation of neural stem cells into neurons	97

Application	Material type	Fabrication method	Function	Reference
Bone	PHB/BC	Salt leaching technique	Promote bone formation in critical size calvarial defects in mice	63
	PHAs/Se-Sr-HA	Solvent casting	A high reduction of the number of Staphylococcus aureus 6538P and Escherichia coli 8739 bacterial cells	36
	PHBV/PLGA	Computer-aided wet-spinning	Support murine preosteoblast cell colonisation and differentiation towards an osteoblastic phenotype	64
	TCP/PHO	Soaking and drying	Enhance the wettability towards more cell-friendly material, enhance the durability of the composites (stress-strain characteristics)	65
	P(3HO-co-3HHX)/HA	Solvent casting‐particulate leaching	Allow migration and proliferation of osteoblasts and mesenchymal cells as well as vascularisation	66
	IM-BM(PLLA+CPC+PHA)	Electrospinning	Reinforce and stabilise incomplete fractures with both mechanical testing and an animal experiment	67
	βTCP/P(3HB)	Polyurethane sponge replica method followed by polymer infiltration	Provide cell-friendly environment, ensure high cell viability, and reduce surface hydrophobicity	68
	PHBV/MBGN/CIN	Emulsion solvent extraction/evaporation	High biological activity and antibacterial performance applied simultaneously in bone tissue engineering	69
Cartilage and joint	Poly(3-hydroxybutyrate)/poly(3-hydroxyoctanoate)	Electrospinning	Allow to produce a cartilage repair kit for clinical use to reduce the risk of developing secondary osteoarthritis	70
	PLCL/PHBV	Emulsion solvent evaporation	Enhance the compressive modulus of PLCL scaffolds, but could also serve as scaffolding structures for cartilaginous tissue formation	71
	PHB-CS/HNT	Electrospinning	Demonstrate a significant increase in cell viability of chondrocytes	72
	PHB-starch/HNTs	Electrospinning	Improve the tensile strength, support cell growth and attachment without any toxicity for biomedical applications	73
	PhaP-RGD/PHBHHx	Solvent evaporation	The biomaterial films of PHBHHx modified with PhaP-RGD fusion protein can promote its biocompatibility with chondrocytes	72
			Promote the proliferation and chondrogenic differentiation of human umbilical-cord-derived mesenchymal stem cells seeded on PHBHHx films	74
			Lead to more homogeneous cell spreading, better cell adhesion, proliferation and chondrogenic differentiation in the scaffolds	75
Skin	PHB/PHB-HV	Electrospinning	Improve vascularisation of engineered bone tissue	76
	PHB/CA	Electrospinning	Improve cell proliferation	77
	PHB/HEAA	Grafting	Promote the proliferation of human fibroblasts	78
	P(3HB-co-4HB)	Freeze-drying	Promote the adhesion of mouse fibroblasts	79
	PHB	Electrospinning	Support the growth of normal human dermal fibroblasts and keratinocytes	80
			Promote the healing of diabetic wounds	81, 82
	PHBA/CA	Electrospinning	Improve fibroblast adhesion and growth	83
Tendon and ligament	PHB/PHBV/PHUE/PHOUE	Electrospinning	Promote cell adhesion and proliferation	84
	PHBHHX	Electrospinning	Promote tendon repair in vivo, which is conducive to restoring weight-bearing and motor function	45
		Make thin films	Promote adhesion and migration of mesenchymal stem cells and tendon cells	85
	PHA	Mesh-augmented single-row RCRs and nonaugmented RCRs	Improve the initial biomechanical repair strength of tears at risk of rupture	86
Cardiovascular	PHA	Electrospinning	Promote the fusion of scaffolds with cells	87
	PHB	Electrospinning	Promote the adhesion and growth of cardiomyocytes and cardiac fibroblasts	88
	PHBHHx/SF	Make thin films	Promote cell adhesion and proliferation	89
	P(3HO)	Cardiac patches	Promote the adhesion and proliferation of neonatal ventricular rat muscle cells	90
Nervous	PHB	Electrospinning	Have high biocompatibility with human mesenchymal stem cells	91
			Promotes the adhesion and differentiation of embryonic cells into nerve cells	92
			Support the survival and regeneration of neurons after spinal cord injury	93
	PHB/PHBV	Electrospinning	Promote the interaction between Schwann cells and scaffolds	93
			Triggers the activity of Schwann cells	94
	PCL-PHB	Electrospinning	Pluripotent stem cells were induced to differentiate into neurons	95
	PHBHHx	Porous nerve conduit	Have good nerve regeneration ability, which can promote the rapid functional recovery of damaged nerves	96
		Electrospinning	Promote the differentiation of neural stem cells into neurons	97

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Recent advances of medical polyhydroxyalkanoates in musculoskeletal system

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