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Polymeric Scaffold Materials for Tissue Engineering

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A special issue of Materials (ISSN 1996-1944). This special issue belongs to the section "Biomaterials".

Deadline for manuscript submissions: closed (10 January 2024) | Viewed by 17098

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Special Issue Editors

Dr. Soonmo Choi

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Guest Editor

Research Institute of Cell Culture, School of Chemical Engineering, Yeungnam University, Gyeongsan-si, Gyeongsangbuk-do, Korea
Interests: tissue engineering; scaffold; biomaterials; tissue regeneration; bio-based polyurethane; biofabrication

Dr. Susanna Sartori

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Guest Editor

Politecnico di Torino, 10129 Turin, Italy
Interests: tissue engineering; tissue models; polyurethanes; surface modification

Dr. Rossella Laurano

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Guest Editor

Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
Interests: biomaterial design; polyurethane synthesis; bioprinting; wound healing; drug delivery systems; multi-stimuli-responsive polymers; bioink design; cell culture; tissue modeling; inflammation modelling; hydrogels
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Special Issue Information

Dear Colleagues,

During recent decades, the design of smart and active materials for scaffold fabrications has attracted a widespread interest, driven by the need to engineer increasingly powerful platforms for tissue engineering and regenerative medicine applications. More recently, advanced biomaterials were also explored for the development of in vitro tissue models, opening up new possibilities in pharma research and toxicology studies. For all these applications, scaffolds are designed to accurately mimic and replicate the composition and the architecture of the native tissues in vitro.

Scaffolds are typically made of polymeric biomaterials and provide the structural support for cell attachment and subsequent tissue development. Scaffold constituent materials play a critical role by acting as synthetic frameworks, and thus their selection represents a crucial issue that is strongly related to the tissue they are expected to replace or replicate. As a consequence, materials strongly affect the resultant scaffolds properties, such as biodegradation behaviour and mechanical and biological properties. Furthermore, bulk or surface functionalization strategies can be adopted in order to better mimic the extracellular matrix composition and enhance cell adhesion.

Emerging fabrication technologies strongly improved the biomimicry of tissue architectures. In particular, 3D bioprinting has introduced new prospectives allowing for the generation of highly controlled structures, which include a more effective reproduction of pore size and the interconnection of native tissue, facilitating cell colonization as well as design reproducibility.

For this Special Issue, we welcome the submission of manuscripts related to polymer synthesis, modification, and evaluation in terms of biomedical applications and processability through the most advanced fabrication techniques. Full papers, communications, and reviews are all welcomed.

Dr. Soonmo Choi
Dr. Susanna Sartori
Dr. Rossella Laurano
Guest Editors

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Keywords

bioactive materials
surface treatment
microfabrication
polymer synthesis
biocompatibilty
materials characterisation
tissue models
regenerative medicine
medical device regulation
bioink design
stimuli-responsive polymers
composite materials
nanomaterials
tissue engineering
biopolymer
surface modification
functional materials

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Published Papers (7 papers)

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Research

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14 pages, 6129 KiB

Open AccessArticle

Biopotentials of Collagen Scaffold Impregnated with Plant-Cell-Derived Epidermal Growth Factor in Defective Bone Healing

by Sher Bahadur Poudel, Govinda Bhattarai, Tae-Ho Kwon and Jeong-Chae Lee

Materials 2023, 16(9), 3335; https://doi.org/10.3390/ma16093335 - 24 Apr 2023

Cited by 4 | Viewed by 1288

Abstract

The combination of scaffolds with recombinant human epidermal growth factor (rhEGF) protein can enhance defective bone healing via synergistic activation to stimulate cellular growth, differentiation, and survival. We examined the biopotentials of an rhEGF-loaded absorbable collagen scaffold (ACS) using a mouse model of calvarial defects, in which the rhEGF was produced from a plant cell suspension culture system because of several systemic advantages. Here, we showed a successful and large-scale production of plant-cell-derived rhEGF protein (p-rhEGF) by introducing an expression vector that cloned with its cDNA under the control of rice α-amylase 3D promoter into rice calli (Oryza sativa L. cv. Dongjin). Implantation with p-rhEGF (5 μg)-loaded ACSs into critical-sized calvarial defects enhanced new bone formation and the expression of osteoblast-specific markers in the defected regions greater than implantation with ACSs alone did. The potency of p-rhEGF-induced bone healing was comparable with that of Escherichia coli-derived rhEGF protein. The exogenous addition of p-rhEGF increased the proliferation of human periodontal ligament cells and augmented the induction of interleukin 8, bone morphogenetic protein 2, and vascular endothelial growth factor in the cells. Collectively, this study demonstrates the successful and convenient production of p-rhEGF, as well as its potency to enhance ACS-mediated bone regeneration by activating cellular responses that are required for wound healing. Full article

(This article belongs to the Special Issue Polymeric Scaffold Materials for Tissue Engineering)

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30 pages, 4474 KiB

Open AccessArticle

Thiol-Ene Photo-Click Hydrogels with Tunable Mechanical Properties Resulting from the Exposure of Different -Ene Moieties through a Green Chemistry

by Rossella Laurano, Monica Boffito, Claudio Cassino, Ludovica Midei, Roberta Pappalardo, Valeria Chiono and Gianluca Ciardelli

Materials 2023, 16(5), 2024; https://doi.org/10.3390/ma16052024 - 28 Feb 2023

Cited by 4 | Viewed by 2723

Abstract

Temperature and light responsiveness are widely exploited stimuli to tune the physico-chemical properties of double network hydrogels. In this work, new amphiphilic poly(ether urethane)s bearing photo-sensitive moieties (i.e., thiol, acrylate and norbornene functionalities) were engineered by exploiting the versatility of poly(urethane) chemistry and carbodiimide-mediated green functionalization procedures. Polymers were synthesized according to optimized protocols maximizing photo-sensitive group grafting while preserving their functionality (approx. 1.0 × 10¹⁹, 2.6 × 10¹⁹ and 8.1 × 10¹⁷ thiol, acrylate and norbornene groups/g_polymer), and exploited to prepare thermo- and Vis-light-responsive thiol-ene photo-click hydrogels (18% w/v, 1:1 thiol:ene molar ratio). Green light-induced photo-curing allowed the achievement of a much more developed gel state with improved resistance to deformation (ca. 60% increase in critical deformation, γL). Triethanolamine addition as co-initiator to thiol-acrylate hydrogels improved the photo-click reaction (i.e., achievement of a better-developed gel state). Differently, L-tyrosine addition to thiol-norbornene solutions slightly hindered cross-linking, resulting in less developed gels with worse mechanical performances (~62% γL decrease). In their optimized composition, thiol-norbornene formulations resulted in prevalent elastic behavior at lower frequency compared to thiol-acrylate gels due to the formation of purely bio-orthogonal instead of heterogeneous gel networks. Our findings highlight that exploiting the same thiol-ene photo-click chemistry, a fine tuning of the gel properties is possible by reacting specific functional groups. Full article

(This article belongs to the Special Issue Polymeric Scaffold Materials for Tissue Engineering)

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18 pages, 4174 KiB

Open AccessArticle

Preparation and Characterization of Polylactic Acid/Nano Hydroxyapatite/Nano Hydroxyapatite/Human Acellular Amniotic Membrane (PLA/nHAp/HAAM) Hybrid Scaffold for Bone Tissue Defect Repair

by Zhilin Jia, Hailin Ma, Jiaqi Liu, Xinyu Yan, Tianqing Liu, Yuen Yee Cheng, Xiangqin Li, Shuo Wu, Jingying Zhang and Kedong Song

Materials 2023, 16(5), 1937; https://doi.org/10.3390/ma16051937 - 26 Feb 2023

Cited by 9 | Viewed by 1928

Abstract

Bone tissue engineering is a novel and efficient repair method for bone tissue defects, and the key step of the bone tissue engineering repair strategy is to prepare non-toxic, metabolizable, biocompatible, bone-induced tissue engineering scaffolds of suitable mechanical strength. Human acellular amniotic membrane (HAAM) is mainly composed of collagen and mucopolysaccharide; it has a natural three-dimensional structure and no immunogenicity. In this study, a polylactic acid (PLA)/Hydroxyapatite (nHAp)/Human acellular amniotic membrane (HAAM) composite scaffold was prepared and the porosity, water absorption and elastic modulus of the composite scaffold were characterized. After that, the cell–scaffold composite was constructed using newborn Sprague Dawley (SD) rat osteoblasts to characterize the biological properties of the composite. In conclusion, the scaffolds have a composite structure of large and small holes with a large pore diameter of 200 μm and a small pore diameter of 30 μm. After adding HAAM, the contact angle of the composite decreases to 38.7°, and the water absorption reaches 249.7%. The addition of nHAp can improve the scaffold’s mechanical strength. The degradation rate of the PLA+nHAp+HAAM group was the highest, reaching 39.48% after 12 weeks. Fluorescence staining showed that the cells were evenly distributed and had good activity on the composite scaffold; the PLA+nHAp+HAAM scaffold has the highest cell viability. The adhesion rate to HAAM was the highest, and the addition of nHAp and HAAM could promote the rapid adhesion of cells to scaffolds. The addition of HAAM and nHAp can significantly promote the secretion of ALP. Therefore, the PLA/nHAp/HAAM composite scaffold can support the adhesion, proliferation and differentiation of osteoblasts in vitro which provide sufficient space for cell proliferation, and is suitable for the formation and development of solid bone tissue. Full article

(This article belongs to the Special Issue Polymeric Scaffold Materials for Tissue Engineering)

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12 pages, 2041 KiB

Open AccessArticle

Long-Term Stability in Electronic Properties of Textile Organic Electrochemical Transistors for Integrated Applications

by Riccardo Manfredi, Filippo Vurro, Michela Janni, Manuele Bettelli, Francesco Gentile, Andrea Zappettini and Nicola Coppedè

Materials 2023, 16(5), 1861; https://doi.org/10.3390/ma16051861 - 24 Feb 2023

Cited by 4 | Viewed by 1725

Abstract

Organic electrochemical transistors (OECTs) have demonstrated themselves to be an efficient interface between living environments and electronic devices in bioelectronic applications. The peculiar properties of conductive polymers allow new performances that overcome the limits of conventional inorganic biosensors, exploiting the high biocompatibility coupled to the ionic interaction. Moreover, the combination with biocompatible and flexible substrates, such as textile fibers, improves the interaction with living cells and allows specific new applications in the biological environment, including real-time analysis of plants’ sap or human sweat monitoring. In these applications, a crucial issue is the lifetime of the sensor device. The durability, long-term stability, and sensitivity of OECTs were studied for two different textile functionalized fiber preparation processes: (i) adding ethylene glycol to the polymer solution, and (ii) using sulfuric acid as a post-treatment. Performance degradation was studied by analyzing the main electronic parameters of a significant number of sensors for a period of 30 days. RGB optical analysis were performed before and after the treatment of the devices. This study shows that device degradation occurs at voltages higher than 0.5 V. The sensors obtained with the sulfuric acid approach exhibit the most stable performances over time. Full article

(This article belongs to the Special Issue Polymeric Scaffold Materials for Tissue Engineering)

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20 pages, 7766 KiB

Open AccessArticle

Towards a Material-by-Design Approach to Electrospun Scaffolds for Tissue Engineering Based on Statistical Design of Experiments (DOE)

by Felicia Carotenuto, Noemi Fiaschini, Paolo Di Nardo and Antonio Rinaldi

Materials 2023, 16(4), 1539; https://doi.org/10.3390/ma16041539 - 12 Feb 2023

Cited by 4 | Viewed by 1886

Abstract

Electrospinning bears great potential for the manufacturing of scaffolds for tissue engineering, consisting of a porous mesh of ultrafine fibers that effectively mimic the extracellular matrix (ECM) and aid in directing stem cell fate. However, for engineering purposes, there is a need to develop material-by-design approaches based on predictive models. In this methodological study, a rational methodology based on statistical design of experiments (DOE) is discussed in detail, yielding heuristic models that capture the linkage between process parameters (Xs) of the electrospinning and scaffold properties (Ys). Five scaffolds made of polycaprolactone are produced according to a 2²-factorial combinatorial scheme where two Xs, i.e., flow rate and applied voltage, are varied between two given levels plus a center point. The scaffolds were characterized to measure a set of properties (Ys), i.e., fiber diameter distribution, porosity, wettability, Young’s modulus, and cell adhesion on murine myoblast C1C12 cells. Simple engineering DOE models were obtained for all Ys. Each Y, for example, the biological response, can be used as a driver for the design process, using the process-property model of interest for accurate interpolation within the design domain, enabling a material-by-design strategy and speeding up the product development cycle. The implications are also illustrated in the context of the design of multilayer scaffolds with microstructural gradients and controlled properties of each layer. The possibility of obtaining statistical models correlating between diverse output properties of the scaffolds is highlighted. Noteworthy, the featured DOE approach can be potentially merged with artificial intelligence tools to manage complexity and it is applicable to several fields including 3D printing. Full article

(This article belongs to the Special Issue Polymeric Scaffold Materials for Tissue Engineering)

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13 pages, 4336 KiB

Open AccessArticle

Systematic Alignment Analysis of Neural Transplant Cells in Electrospun Nanofibre Scaffolds

by Aina Mogas Barcons, Farhana Chowdhury, Divya M. Chari and Christopher Adams

Materials 2023, 16(1), 124; https://doi.org/10.3390/ma16010124 - 23 Dec 2022

Cited by 1 | Viewed by 1970

Abstract

Spinal cord injury is debilitating with functional loss often permanent due to a lack of neuro-regenerative or neuro-therapeutic strategies. A promising approach to enhance biological function is through implantation of tissue engineered constructs, to offer neural cell replacement and reconstruction of the functional neuro-architecture. A key goal is to achieve spatially targeted guidance of regenerating tissue across the lesion site to achieve an aligned tissue structure lost as a consequence of injury. Electrospun nanofibres mimic the nanoscale architecture of the spinal cord, can be readily aligned, functionalised with pro-regenerative molecules and incorporated into implantable matrices to provide topographical cues. Crucially, electrospun nanofibers are routinely manufactured at a scale required for clinical use. Although promising, few studies have tested whether electrospun nanofibres can guide targeted spatial growth of clinically relevant neural stem/precursor populations. The alignment fate of daughter cells (derived from the pre-aligned parent cells) has also received limited attention. Further, a standardised quantification methodology to correlate neural cell alignment with topographical cues is not available. We have adapted an image analysis technique to quantify nanofibre-induced alignment of neural cells. Using this method, we show that two key neural stem/precursor populations of clinical relevance (namely, neural stem cells (NSCs) and oligodendrocyte precursor cells), reproducibly orientate their growth to aligned, high-density electrospun nanofiber meshes, but not randomly distributed ones. Daughter populations derived from aligned NSCs (neurons and astrocytes) maintained their alignment following differentiation, but oligodendrocytes did not. Our data show that pre-aligned transplant populations can be used to generate complex, multicellular aligned-fibre constructs for neural implantation. Full article

(This article belongs to the Special Issue Polymeric Scaffold Materials for Tissue Engineering)

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Review

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24 pages, 6115 KiB

Open AccessReview

Extrusion 3D (Bio)Printing of Alginate-Gelatin-Based Composite Scaffolds for Skeletal Muscle Tissue Engineering

by Surendrasingh Y. Sonaye, Elif G. Ertugral, Chandrasekhar R. Kothapalli and Prabaha Sikder

Materials 2022, 15(22), 7945; https://doi.org/10.3390/ma15227945 - 10 Nov 2022

Cited by 28 | Viewed by 4367

Abstract

Volumetric muscle loss (VML), which involves the loss of a substantial portion of muscle tissue, is one of the most serious acute skeletal muscle injuries in the military and civilian communities. The injured area in VML may be so severely affected that the body loses its innate capacity to regenerate new functional muscles. State-of-the-art biofabrication methods such as bioprinting provide the ability to develop cell-laden scaffolds that could significantly expedite tissue regeneration. Bioprinted cell-laden scaffolds can mimic the extracellular matrix and provide a bioactive environment wherein cells can spread, proliferate, and differentiate, leading to new skeletal muscle tissue regeneration at the defect site. In this study, we engineered alginate–gelatin composite inks that could be used as bioinks. Then, we used the inks in an extrusion printing method to develop design-specific scaffolds for potential VML treatment. Alginate concentration was varied between 4–12% w/v, while the gelatin concentration was maintained at 6% w/v. Rheological analysis indicated that the alginate–gelatin inks containing 12% w/v alginate and 6% w/v gelatin were most suitable for developing high-resolution scaffolds with good structural fidelity. The printing pressure and speed appeared to influence the printing accuracy of the resulting scaffolds significantly. All the hydrogel inks exhibited shear thinning properties and acceptable viscosities, though 8–12% w/v alginate inks displayed properties ideal for printing and cell proliferation. Alginate content, crosslinking concentration, and duration played significant roles (p < 0.05) in influencing the scaffolds’ stiffness. Alginate scaffolds (12% w/v) crosslinked with 300, 400, or 500 mM calcium chloride (CaCl₂) for 15 min yielded stiffness values in the range of 45–50 kPa, i.e., similar to skeletal muscle. The ionic strength of the crosslinking concentration and the alginate content significantly (p < 0.05) affected the swelling and degradation behavior of the scaffolds. Higher crosslinking concentration and alginate loading enhanced the swelling capacity and decreased the degradation kinetics of the printed scaffolds. Optimal CaCl₂ crosslinking concentration (500 mM) and alginate content (12% w/v) led to high swelling (70%) and low degradation rates (28%) of the scaffolds. Overall, the results indicate that 12% w/v alginate and 6% w/v gelatin hydrogel inks are suitable as bioinks, and the printed scaffolds hold good potential for treating skeletal muscle defects such as VML. Full article

(This article belongs to the Special Issue Polymeric Scaffold Materials for Tissue Engineering)

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