TY - JOUR
T1 - Novel hybrid biocomposites for tendon grafts
T2 - The addition of silk to polydioxanone and poly(lactide-co-caprolactone) enhances material properties, in vitro and in vivo biocompatibility
AU - Shiroud Heidari, Behzad
AU - Muiños Lopez, Emma
AU - Harrington, Emma
AU - Ruan, Rui
AU - Chen, Peilin
AU - Davachi, Seyed Mohammad
AU - Allardyce, Benjamin
AU - Rajkhowa, Rangam
AU - Dilley, Rodney
AU - Granero-Moltó, Froilán
AU - De-Juan-Pardo, Elena M.
AU - Zheng, Minghao
AU - Doyle, Barry
N1 - Funding Information:
The authors acknowledge the facilities, scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy, Characterisation & Analysis (CMCA), the University of Western Australia (UWA), a facility funded by the University, State and Commonwealth Governments. The authors would like to thank Professor Hong Yang from UWA School of Engineering to provide the thermal analysis instrument for this project. The authors also gratefully acknowledge funding from the Australian Research Council ( IC170100061 ) through the Centre for Personalised Therapeutics Technologies, and the Science-Industry PhD Fellowship from the Western Australia Department of Jobs, Tourism, Science and Innovation (awarded to B.S.H.).
Funding Information:
In recent years, different hybrid biocomposites based on natural and synthetic biopolymers have been developed to achieve the optimal balance between the materials’ properties for the fabrication of functional scaffolds. Poly(ε-caprolactone) (PCL), polylactide (PLA) and poy(lactic-co-glycolide) (PLGA) are the most common synthetic biopolymers blended with natural biopolymers, mostly collagen and gelatine, to promote biocompatibility and biofunctionality of TL scaffolds [ 2–5]. For instance, PLLA/collagen blends (PLLA/Coll-75/25, PLLA/Coll-50/50) were prepared and used to fabricate electrospun tendon scaffolds [6]. PLLA/Coll-75/25 showed more desirable mechanical properties after incubation in PBS for 14 days, compared to the PLLA/Coll-50/50 [6]. PCL/collagen and PLA/collagen were co-electrospun to create a scaffold for the tissue engineering of muscle-tendon junctions (MTJ), where the collagen greatly improved biocompatibility and provided suitable mechanical properties matched with the native MTJ [5]. Gelatine was also blended with PCL to promote proliferation, adhesion and tenogenic differentiation of fibroblasts in vitro [7,8]. Furthermore, it was shown that tendon scaffolds made of PCL/gelatine could support the regenerated tissue of injured patellar tendons to restore biomechanical strength in a rabbit model [8]. Most of those composites have been developed by mixing materials in a solvent, mainly because solution electrospinning is an accessible method for TL scaffold fabrication [9].The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B.S.H. and B.J.D. are inventors on a patent application (PCT/AU2021/050782) titled “Biocompatible polymer compositions” submitted by The University of Western Australia that covers the material composition described in this work. The other authors have no conflicts of interest to declare.The authors acknowledge the facilities, scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy, Characterisation & Analysis (CMCA), the University of Western Australia (UWA), a facility funded by the University, State and Commonwealth Governments. The authors would like to thank Professor Hong Yang from UWA School of Engineering to provide the thermal analysis instrument for this project. The authors also gratefully acknowledge funding from the Australian Research Council (IC170100061) through the Centre for Personalised Therapeutics Technologies, and the Science-Industry PhD Fellowship from the Western Australia Department of Jobs, Tourism, Science and Innovation (awarded to B.S.H.).
Publisher Copyright:
© 2023 The Authors
PY - 2023/7
Y1 - 2023/7
N2 - Biopolymers play a critical role as scaffolds used in tendon and ligament (TL) regeneration. Although advanced biopolymer materials have been proposed with optimised mechanical properties, biocompatibility, degradation, and processability, it is still challenging to find the right balance between these properties. Here, we aim to develop novel hybrid biocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL) and silk to produce high-performance grafts suitable for TL tissue repair. Biocomposites containing 1–15% of silk were studied through a range of characterisation techniques. We then explored biocompatibility through in vitro and in vivo studies using a mouse model. We found that adding up to 5% silk increases the tensile properties, degradation rate and miscibility between PDO and LCL phases without agglomeration of silk inside the composites. Furthermore, addition of silk increases surface roughness and hydrophilicity. In vitro experiments show that the silk improved attachment of tendon-derived stem cells and proliferation over 72 h, while in vivo studies indicate that the silk can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. Finally, we selected a promising biocomposite and created a prototype TL graft based on extruded fibres. We found that the tensile properties of both individual fibres and braided grafts could be suitable for anterior cruciate ligament (ACL) repair applications.
AB - Biopolymers play a critical role as scaffolds used in tendon and ligament (TL) regeneration. Although advanced biopolymer materials have been proposed with optimised mechanical properties, biocompatibility, degradation, and processability, it is still challenging to find the right balance between these properties. Here, we aim to develop novel hybrid biocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL) and silk to produce high-performance grafts suitable for TL tissue repair. Biocomposites containing 1–15% of silk were studied through a range of characterisation techniques. We then explored biocompatibility through in vitro and in vivo studies using a mouse model. We found that adding up to 5% silk increases the tensile properties, degradation rate and miscibility between PDO and LCL phases without agglomeration of silk inside the composites. Furthermore, addition of silk increases surface roughness and hydrophilicity. In vitro experiments show that the silk improved attachment of tendon-derived stem cells and proliferation over 72 h, while in vivo studies indicate that the silk can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. Finally, we selected a promising biocomposite and created a prototype TL graft based on extruded fibres. We found that the tensile properties of both individual fibres and braided grafts could be suitable for anterior cruciate ligament (ACL) repair applications.
KW - Anterior cruciate ligament
KW - Biocomposite
KW - Biodegradable scaffolds
KW - Fibre extrusion
KW - Silk
KW - Tendon graft
UR - http://www.scopus.com/inward/record.url?scp=85147961483&partnerID=8YFLogxK
U2 - 10.1016/j.bioactmat.2023.02.003
DO - 10.1016/j.bioactmat.2023.02.003
M3 - Article
C2 - 36844365
AN - SCOPUS:85147961483
SN - 2452-199X
VL - 25
SP - 291
EP - 306
JO - Bioactive Materials
JF - Bioactive Materials
ER -