Bioengineering

Research

Jump to: Review

14 pages, 5830 KiB

Open AccessArticle

Engineering Skeletal Muscle Grafts with PAX7::GFP-Sorted Human Pluripotent Stem Cell-Derived Myogenic Progenitors on Fibrin Microfiber Bundles for Tissue Regeneration

by Sarah M. Somers, Jordana Gilbert-Honick, In Young Choi, Emily K. W. Lo, HoTae Lim, Shaquielle Dias, Kathryn R. Wagner, Hai-Quan Mao, Patrick Cahan, Gabsang Lee and Warren L. Grayson

Bioengineering 2022, 9(11), 693; https://doi.org/10.3390/bioengineering9110693 - 15 Nov 2022

Cited by 6 | Viewed by 2601

Abstract

Tissue engineering strategies that combine human pluripotent stem cell-derived myogenic progenitors (hPDMs) with advanced biomaterials provide promising tools for engineering 3D skeletal muscle grafts to model tissue development in vitro and promote muscle regeneration in vivo. We recently demonstrated (i) the potential for [...] Read more.

Tissue engineering strategies that combine human pluripotent stem cell-derived myogenic progenitors (hPDMs) with advanced biomaterials provide promising tools for engineering 3D skeletal muscle grafts to model tissue development in vitro and promote muscle regeneration in vivo. We recently demonstrated (i) the potential for obtaining large numbers of hPDMs using a combination of two small molecules without the overexpression of transgenes and (ii) the application of electrospun fibrin microfiber bundles for functional skeletal muscle restoration following volumetric muscle loss. In this study, we aimed to demonstrate that the biophysical cues provided by the fibrin microfiber bundles induce hPDMs to form engineered human skeletal muscle grafts containing multinucleated myotubes that express desmin and myosin heavy chains and that these grafts could promote regeneration following skeletal muscle injuries. We tested a genetic PAX7 reporter line (PAX7::GFP) to sort for more homogenous populations of hPDMs. RNA sequencing and gene set enrichment analyses confirmed that PAX7::GFP-sorted hPDMs exhibited high expression of myogenic genes. We tested engineered human skeletal muscle grafts derived from PAX7::GFP-sorted hPDMs within in vivo skeletal muscle defects by assessing myogenesis, engraftment and immunogenicity using immunohistochemical staining. The PAX7::GFP-sorted groups had moderately high vascular infiltration and more implanted cell association with embryonic myosin heavy chain (eMHC) regions, suggesting they induced pro-regenerative microenvironments. These findings demonstrated the promise for the use of PAX7::GFP-sorted hPDMs on fibrin microfiber bundles and provided some insights for improving the cell–biomaterial system to stimulate more robust in vivo skeletal muscle regeneration. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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13 pages, 22352 KiB

Open AccessArticle

Biocompatible Nanocomposite Coatings Deposited via Layer-by-Layer Assembly for the Mechanical Reinforcement of Highly Porous Interconnected Tissue-Engineered Scaffolds

by Aoife McFerran, Mary Josephine McIvor, Patrick Lemoine, Brian J. Meenan and Jonathan G. Acheson

Bioengineering 2022, 9(10), 585; https://doi.org/10.3390/bioengineering9100585 - 20 Oct 2022

Cited by 5 | Viewed by 2167

Abstract

Tissue-engineered (TE) scaffolds provide an ‘off-the-shelf’ alternative to autograft procedures and can potentially address their associated complications and limitations. The properties of TE scaffolds do not always match the surrounding bone, often sacrificing porosity for improved compressive strength. Previously, the layer-by-layer (LbL) assembly [...] Read more.

Tissue-engineered (TE) scaffolds provide an ‘off-the-shelf’ alternative to autograft procedures and can potentially address their associated complications and limitations. The properties of TE scaffolds do not always match the surrounding bone, often sacrificing porosity for improved compressive strength. Previously, the layer-by-layer (LbL) assembly technique was used to deposit nanoclay containing multilayers capable of improving the mechanical properties of open-cell structures without greatly affecting the porosity. However, the previous coatings studied contained poly(ethylenimine) (PEI), which is known to be cytotoxic due to the presence of amine groups, rendering it unsuitable for use in biomedical applications. In this work, poly(diallydimethylammonium chloride) (PDDA)- and chitosan (CHI)-based polyelectrolyte systems were investigated for the purpose of nanoclay addition as an alternative to PEI-based polyelectrolyte systems. Nanocomposite coatings comprising of PEI, poly(acrylic acid) (PAA), Na+ montmorillonite (NC), PDDA, CHI and sodium alginate (ALG) were fabricated. The coatings were deposited in the following manner: (PEI/PAA/PEI/NC), PEI-(PDDA/PAA/PDDA/NC) and (CHI/ALG/CHI/ALG). Results from scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analyses demonstrated that the nanoclay was successfully incorporated into each polymer bilayer system, creating a nanocomposite coating. Each coating was successful at tailoring the elastic modulus of the open-cell structures, with polyurethane foams exhibiting an increase from 0.15 ± 0.10 MPa when uncoated to 5.51 ± 0.40 MPa, 6.01 ± 0.36 MPa and 2.61 ± 0.41 MPa when coated with (PEI/PAA/PEI/NC), PEI-(PDDA/PAA/PDDA/NC) and (CHI/ALG/CHI/ALG), respectively. Several biological studies were conducted to determine the cytotoxicity of the coatings, including a resazurin reduction assay, scanning electron microscopy and fluorescent staining of the cell-seeded substrates. In this work, the PDDA-based system exhibited equivalent physical and mechanical properties to the PEI-based system and was significantly more biocompatible, making it a much more suitable alternative for biomaterial applications. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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16 pages, 3275 KiB

Open AccessArticle

Effects of Different Titanium Surfaces Created by 3D Printing Methods, Particle Sizes, and Acid Etching on Protein Adsorption and Cell Adhesion, Proliferation, and Differentiation

by Max Jin, Haseung Chung, Patrick Kwon and Adil Akkouch

Bioengineering 2022, 9(10), 514; https://doi.org/10.3390/bioengineering9100514 - 28 Sep 2022

Cited by 4 | Viewed by 2270

Abstract

The surfaces of 3D printed titanium prostheses have major impacts on the clinical performance of the prostheses. To investigate the surface effects of the products generated by 3D printed titanium on osseointegration, six surface types of titanium discs produced by the direct metal [...] Read more.

The surfaces of 3D printed titanium prostheses have major impacts on the clinical performance of the prostheses. To investigate the surface effects of the products generated by 3D printed titanium on osseointegration, six surface types of titanium discs produced by the direct metal laser sintering (DMLS) and electron beam melting (EBM) methods, with two sizes of titanium particles and post-printing acid etching, were used to examine the surface topography and to explore the protein adsorption, pro-inflammatory cytokine gene expressions, and MC3T3-E1 cell adhesion, proliferation, and differentiation. The EBM-printed disc showed a stripy and smooth surface without evidence of the particles used, while the DMLS surface contained many particles. After acid etching, small particles on the DMLS surface were removed, whereas the large particles were left. Moreover, distinct proteins with low molecular weights were attached to the 3D printed titanium discs but not to the pre-printing titanium particles. The small titanium particles stimulated the highest TNF-α and IL-6 gene expressions at 24 h. The alizarin red content and osteocalcin gene expression at day 21 were the highest in the groups of acid-etched discs printed by DMLS with the small particles and by EBM. Therefore, the acid-treated surfaces without particles favor osteogenic differentiation. The surface design of 3D printed titanium prostheses should be based on their clinical applications. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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16 pages, 3315 KiB

Open AccessArticle

Human Adipose-Derived Stromal Cells Delivered on Decellularized Muscle Improve Muscle Regeneration and Regulate RAGE and P38 MAPK

by Lucas C. Olson, James T. Redden, LaStar Gilliam, Tri M. Nguyen, Josephina A. Vossen, David J. Cohen, Zvi Schwartz and Michael J. McClure

Bioengineering 2022, 9(9), 426; https://doi.org/10.3390/bioengineering9090426 - 30 Aug 2022

Cited by 5 | Viewed by 2379

Abstract

Volumetric muscle loss (VML) is the acute loss of muscle mass due to trauma. Such injuries occur primarily in the extremities and are debilitating, as there is no clinical treatment to restore muscle function. Pro-inflammatory advanced glycation end-products (AGEs) and the soluble receptor [...] Read more.

Volumetric muscle loss (VML) is the acute loss of muscle mass due to trauma. Such injuries occur primarily in the extremities and are debilitating, as there is no clinical treatment to restore muscle function. Pro-inflammatory advanced glycation end-products (AGEs) and the soluble receptor for advanced glycation end-products (RAGE) are known to increase in acute trauma patient’s serum and are correlated with increased injury severity. However, it is unclear whether AGEs and RAGE increase in muscle post-trauma. To test this, we used decellularized muscle matrix (DMM), a pro-myogenic, non-immunogenic extracellular matrix biomaterial derived from skeletal muscle. We delivered adipose-derived stromal cells (ASCs) and primary myoblasts to support myogenesis and immunomodulation (N = 8 rats/group). DMM non-seeded and seeded grafts were compared to empty defect and sham controls. Then, 56 days after surgery muscle force was assessed, histology characterized, and protein levels for AGEs, RAGE, p38 MAPK, and myosin heavy chains were measured. Overall, our data showed improved muscle regeneration in ASC-treated injury sites and a regulation of RAGE and p38 MAPK signaling, while myoblast-treated injuries resulted in minor improvements. Taken together, these results suggested that ASCs combined with DMM provides a pro-myogenic microenvironment with immunomodulatory capabilities and indicates further exploration of RAGE signaling in VML. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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20 pages, 4771 KiB

Open AccessArticle

The Effect of Mesenchymal Stem Cells, Adipose Tissue Derived Stem Cells, and Cellular Stromal Vascular Fraction on the Repair of Acute Anal Sphincter Injury in Rats

by Wenbin Chen, Zijian He, Shuyu Li, Zixin Wu, Jin Tan, Weifeng Yang, Guanwei Li, Xiaoting Pan, Yuying Liu, Feng-Juan Lyu and Wanglin Li

Bioengineering 2022, 9(7), 318; https://doi.org/10.3390/bioengineering9070318 - 15 Jul 2022

Cited by 7 | Viewed by 2754

Abstract

Background: Anal sphincter incontinence (ASI) can cause a serious decline in the quality of life and can cause a socioeconomic burden. Studies have shown that bone marrow mesenchymal stem cells (MSC) have significant therapeutic effects on ASI, but the cost and risk of [...] Read more.

Background: Anal sphincter incontinence (ASI) can cause a serious decline in the quality of life and can cause a socioeconomic burden. Studies have shown that bone marrow mesenchymal stem cells (MSC) have significant therapeutic effects on ASI, but the cost and risk of MSC harvest limit their further application. In contrast, adipose tissue derived stem cells (ADSC) and cellular stromal vascular fraction (CSVF) as stem cell sources have multipotency and the advantage of easy harvest. Objective: Here we aim to investigate the effects of ADSC and CSVF on treating ASI and compare them to that of bone marrow MSC. Methods: Bone marrow MSC, ADSC, and CSVF were obtained and labeled with green fluorescent protein (GFP), and CSVF was labeled with DIL. Sprague Dawley (SD) rats were divided into 5 groups. Four groups were injected with 0.2 mL phosphate buffer saline (PBS), 1 × 10⁷/0.2 mL of MSC, ADSC, or CSVF, respectively, after model establishment. The control group received no treatment. The repair was assessed by anal functional tests and immunostaining on day 5 and day 10 after injection. Results: MSC, ADSC, and CSVF significantly promoted tissue repair and the recovery of muscle contraction and electromyographic activity in ASI. The generation of myosatellite cells by injected MSC, ADSC, and CSVF was found in the wounded area. On day 5, CSVF showed highest therapeutic effect, while on day 10, MSC and ADSC showed higher therapeutic effects than CSVF. When comparing the effects of MSC and ADSC, ADSC was slightly better than MSC in the indexes of anal pressure, etc. Conclusion: ADSC and CVSF are alternative stem cell sources for ASI repair. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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18 pages, 3121 KiB

Open AccessArticle

Impact of Electrospun Piezoelectric Core–Shell PVDFhfp/PDMS Mesh on Tenogenic and Inflammatory Gene Expression in Human Adipose-Derived Stem Cells: Comparison of Static Cultivation with Uniaxial Cyclic Tensile Stretching

by Walter Baumgartner, Petra Wolint, Silvan Hofmann, Cléa Nüesch, Maurizio Calcagni, Marzia Brunelli and Johanna Buschmann

Bioengineering 2022, 9(1), 21; https://doi.org/10.3390/bioengineering9010021 - 8 Jan 2022

Cited by 8 | Viewed by 2976

Abstract

Specific microenvironments can trigger stem cell tenogenic differentiation, such as specific substrates or dynamic cell cultivation. Electrospun meshes composed by core–shell fibers (random or aligned; PDMS core; piezoelectric PVDFhfp shell) were fabricated by coaxial electrospinning. Elastic modulus and residual strain were assessed. Human [...] Read more.

Specific microenvironments can trigger stem cell tenogenic differentiation, such as specific substrates or dynamic cell cultivation. Electrospun meshes composed by core–shell fibers (random or aligned; PDMS core; piezoelectric PVDFhfp shell) were fabricated by coaxial electrospinning. Elastic modulus and residual strain were assessed. Human ASCs were seeded on such scaffolds either under static conditions for 1 week or with subsequent 10% dynamic stretching for 10,800 cycles (1 Hz, 3 h), assessing load elongation curves in a Bose^® bioreactor system. Gene expression for tenogenic expression, extracellular matrix, remodeling, pro-fibrotic and inflammatory marker genes were assessed (PCR). For cell-seeded meshes, the E modulus increased from 14 ± 3.8 MPa to 31 ± 17 MPa within 3 h, which was not observed for cell-free meshes. Random fibers resulted in higher tenogenic commitment than aligned fibers. Dynamic cultivation significantly enhanced pro-inflammatory markers. Compared to ASCs in culture flasks, ASCs on random meshes under static cultivation showed a significant upregulation of Mohawk, Tenascin-C and Tenomodulin. The tenogenic commitment expressed by human ASCs in contact with random PVDFhfp/PDMS paves the way for using this novel highly elastic material as an implant to be wrapped around a lacerated tendon, envisioned as a functional anti-adhesion membrane. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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24 pages, 3734 KiB

Open AccessArticle

Conductive Bioimprint Using Soft Lithography Technique Based on PEDOT:PSS for Biosensing

by Nor Azila Abd. Wahid, Azadeh Hashemi, John J. Evans and Maan M. Alkaisi

Bioengineering 2021, 8(12), 204; https://doi.org/10.3390/bioengineering8120204 - 9 Dec 2021

Cited by 5 | Viewed by 3493

Abstract

Culture platform surface topography plays an important role in the regulation of biological cell behaviour. Understanding the mechanisms behind the roles of surface topography in cell response are central to many developments in a Lab on a Chip, medical implants and biosensors. In [...] Read more.

Culture platform surface topography plays an important role in the regulation of biological cell behaviour. Understanding the mechanisms behind the roles of surface topography in cell response are central to many developments in a Lab on a Chip, medical implants and biosensors. In this work, we report on a novel development of a biocompatible conductive hydrogel (CH) made of poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and gelatin with bioimprinted surface features. The bioimprinted CH offers high conductivity, biocompatibility and high replication fidelity suitable for cell culture applications. The bioimprinted conductive hydrogel is developed to investigate biological cells’ response to their morphological footprint and study their growth, adhesion, cell–cell interactions and proliferation as a function of conductivity. Moreover, optimization of the conductive hydrogel mixture plays an important role in achieving high imprinting resolution and conductivity. The reason behind choosing a conducive hydrogel with high resolution surface bioimprints is to improve cell monitoring while mimicking cells’ natural physical environment. Bioimprints which are a 3D replication of cellular morphology have previously been shown to promote cell attachment, proliferation, differentiation and even cell response to drugs. The conductive substrate, on the other hand, enables cell impedance to be measured and monitored, which is indicative of cell viability and spread. Two dimensional profiles of the cross section of a single cell taken via Atomic Force Microscopy (AFM) from the fixed cell on glass, and its replicas on polydimethylsiloxane (PDMS) and conductive hydrogel (CH) show unprecedented replication of cellular features with an average replication fidelity of more than 90%. Furthermore, crosslinking CH films demonstrated a significant increase in electrical conductivity from 10⁻⁶ S/cm to 1 S/cm. Conductive bioimprints can provide a suitable platform for biosensing applications and potentially for monitoring implant-tissue reactions in medical devices. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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14 pages, 3596 KiB

Open AccessArticle

Biocompatible Customized 3D Bone Scaffolds Treated with CRFP, an Osteogenic Peptide

by Vamiq M. Mustahsan, Amith Anugu, David E. Komatsu, Imin Kao and Srinivas Pentyala

Bioengineering 2021, 8(12), 199; https://doi.org/10.3390/bioengineering8120199 - 30 Nov 2021

Cited by 6 | Viewed by 3424

Abstract

Background: Currently used synthetic bone graft substitutes (BGS) are either too weak to bear the principal load or if metallic, they can support loading, but can lead to stress shielding and are unable to integrate fully. In this study, we developed biocompatible, 3D [...] Read more.

Background: Currently used synthetic bone graft substitutes (BGS) are either too weak to bear the principal load or if metallic, they can support loading, but can lead to stress shielding and are unable to integrate fully. In this study, we developed biocompatible, 3D printed scaffolds derived from µCT images of the bone that can overcome these issues and support the growth of osteoblasts. Methods: Cylindrical scaffolds were fabricated with acrylonitrile butadiene styrene (ABS) and Stratasys^® MED 610 (MED610) materials. The 3D-printed scaffolds were seeded with Mus musculus calvaria cells (MC3T3). After the cells attained confluence, osteogenesis was induced with and without the addition of calcitonin receptor fragment peptide (CRFP) and the bone matrix production was analyzed. Mechanical compression testing was carried out to measure compressive strength, stiffness, and elastic modulus. Results: For the ABS scaffolds, there was a 9.8% increase in compressive strength (p < 0.05) in the scaffolds with no pre-coating and the treatment with CRFP, compared to non-treated scaffolds. Similarly, MED610 scaffolds treated with CRFP showed an 11.9% (polylysine pre-coating) and a 20% (no pre-coating) increase (p < 0.01) in compressive strength compared to non-treated scaffolds. Conclusions: MED610 scaffolds are excellent BGS as they support osteoblast growth and show enhanced bone growth with enhanced compressive strength when augmented with CRFP. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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22 pages, 8146 KiB

Open AccessArticle

Dual Network Composites of Poly(vinyl alcohol)-Calcium Metaphosphate/Alginate with Osteogenic Ions for Bone Tissue Engineering in Oral and Maxillofacial Surgery

by Lilis Iskandar, Lucy DiSilvio, Jonathan Acheson and Sanjukta Deb

Bioengineering 2021, 8(8), 107; https://doi.org/10.3390/bioengineering8080107 - 28 Jul 2021

Cited by 4 | Viewed by 3999

Abstract

Despite considerable advances in biomaterials-based bone tissue engineering technologies, autografts remain the gold standard for rehabilitating critical-sized bone defects in the oral and maxillofacial (OMF) region. A majority of advanced synthetic bone substitutes (SBS’s) have not transcended the pre-clinical stage due to inferior [...] Read more.

Despite considerable advances in biomaterials-based bone tissue engineering technologies, autografts remain the gold standard for rehabilitating critical-sized bone defects in the oral and maxillofacial (OMF) region. A majority of advanced synthetic bone substitutes (SBS’s) have not transcended the pre-clinical stage due to inferior clinical performance and translational barriers, which include low scalability, high cost, regulatory restrictions, limited advanced facilities and human resources. The aim of this study is to develop clinically viable alternatives to address the challenges of bone tissue regeneration in the OMF region by developing ‘dual network composites’ (DNC’s) of calcium metaphosphate (CMP)—poly(vinyl alcohol) (PVA)/alginate with osteogenic ions: calcium, zinc and strontium. To fabricate DNC’s, single network composites of PVA/CMP with 10% (w/v) gelatine particles as porogen were developed using two freeze–thawing cycles and subsequently interpenetrated by guluronate-dominant sodium alginate and chelated with calcium, zinc or strontium ions. Physicochemical, compressive, water uptake, thermal, morphological and in vitro biological properties of DNC’s were characterised. The results demonstrated elastic 3D porous scaffolds resembling a ‘spongy bone’ with fluid absorbing capacity, easily sculptable to fit anatomically complex bone defects, biocompatible and osteoconductive in vitro, thus yielding potentially clinically viable for SBS alternatives in OMF surgery. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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Review

Jump to: Research

22 pages, 1040 KiB

Open AccessReview

Tissue Engineering Applied to Skeletal Muscle: Strategies and Perspectives

by Ana Luisa Lopes Martins, Luciana Pastena Giorno and Arnaldo Rodrigues Santos, Jr.

Bioengineering 2022, 9(12), 744; https://doi.org/10.3390/bioengineering9120744 - 30 Nov 2022

Cited by 7 | Viewed by 3799

Abstract

Muscle tissue is formed by elongated and contractile cells with specific morphofunctional characteristics. Thus, it is divided into three basic types: smooth muscle tissue, cardiac striated muscle tissue and skeletal striated muscle tissue. The striated skeletal muscle tissue presents high plasticity, regeneration and [...] Read more.

Muscle tissue is formed by elongated and contractile cells with specific morphofunctional characteristics. Thus, it is divided into three basic types: smooth muscle tissue, cardiac striated muscle tissue and skeletal striated muscle tissue. The striated skeletal muscle tissue presents high plasticity, regeneration and growth capacity due to the presence of satellite cells, quiescent myoblasts that are activated in case of injury to the tissue and originate new muscle fibers when they differentiate. In more severe deficiencies or injuries there is a loss of their regenerative capacity, thus compromising the body’s functionality at different levels. Tissue engineering studies the development of biomaterials capable of stimulating the recovery of cellular activity in injured body tissues, as well as the activity of cells with muscle differentiation potential in injury repair. However, the need for three-dimensional re-assembly in a complex organization makes it difficult to mimic this tissue and fully regenerate it for the sake of precise and effective movements. Thus, this article aims to provide a narrative review of tissue engineering strategies applied to the regeneration of skeletal muscle, in a critical evaluation of research, whether aimed at injury or atrophies such as spinal muscular atrophy. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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33 pages, 4118 KiB

Open AccessEditor’s ChoiceReview

3D-Printing for Critical Sized Bone Defects: Current Concepts and Future Directions

by Cory K. Mayfield, Mina Ayad, Elizabeth Lechtholz-Zey, Yong Chen and Jay R. Lieberman

Bioengineering 2022, 9(11), 680; https://doi.org/10.3390/bioengineering9110680 - 11 Nov 2022

Cited by 24 | Viewed by 4878

Abstract

The management and definitive treatment of segmental bone defects in the setting of acute trauma, fracture non-union, revision joint arthroplasty, and tumor surgery are challenging clinical problems with no consistently satisfactory solution. Orthopaedic surgeons are developing novel strategies to treat these problems, including [...] Read more.

The management and definitive treatment of segmental bone defects in the setting of acute trauma, fracture non-union, revision joint arthroplasty, and tumor surgery are challenging clinical problems with no consistently satisfactory solution. Orthopaedic surgeons are developing novel strategies to treat these problems, including three-dimensional (3D) printing combined with growth factors and/or cells. This article reviews the current strategies for management of segmental bone loss in orthopaedic surgery, including graft selection, bone graft substitutes, and operative techniques. Furthermore, we highlight 3D printing as a technology that may serve a major role in the management of segmental defects. The optimization of a 3D-printed scaffold design through printing technique, material selection, and scaffold geometry, as well as biologic additives to enhance bone regeneration and incorporation could change the treatment paradigm for these difficult bone repair problems. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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25 pages, 5165 KiB

Open AccessReview

Gelatin Methacryloyl Hydrogels for Musculoskeletal Tissue Regeneration

by Yang-Hee Kim, Jonathan I. Dawson, Richard O. C. Oreffo, Yasuhiko Tabata, Dhiraj Kumar, Conrado Aparicio and Isha Mutreja

Bioengineering 2022, 9(7), 332; https://doi.org/10.3390/bioengineering9070332 - 21 Jul 2022

Cited by 11 | Viewed by 5165

Abstract

Musculoskeletal disorders are a significant burden on the global economy and public health. Hydrogels have significant potential for enhancing the repair of damaged and injured musculoskeletal tissues as cell or drug delivery systems. Hydrogels have unique physicochemical properties which make them promising platforms [...] Read more.

Musculoskeletal disorders are a significant burden on the global economy and public health. Hydrogels have significant potential for enhancing the repair of damaged and injured musculoskeletal tissues as cell or drug delivery systems. Hydrogels have unique physicochemical properties which make them promising platforms for controlling cell functions. Gelatin methacryloyl (GelMA) hydrogel in particular has been extensively investigated as a promising biomaterial due to its tuneable and beneficial properties and has been widely used in different biomedical applications. In this review, a detailed overview of GelMA synthesis, hydrogel design and applications in regenerative medicine is provided. After summarising recent progress in hydrogels more broadly, we highlight recent advances of GelMA hydrogels in the emerging fields of musculoskeletal drug delivery, involving therapeutic drugs (e.g., growth factors, antimicrobial molecules, immunomodulatory drugs and cells), delivery approaches (e.g., single-, dual-release system), and material design (e.g., addition of organic or inorganic materials, 3D printing). The review concludes with future perspectives and associated challenges for developing local drug delivery for musculoskeletal applications. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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31 pages, 6146 KiB

Open AccessReview

Biodegradable and Biocompatible Adhesives for the Effective Stabilisation, Repair and Regeneration of Bone

by Antzela Tzagiollari, Helen O. McCarthy, Tanya J. Levingstone and Nicholas J. Dunne

Bioengineering 2022, 9(6), 250; https://doi.org/10.3390/bioengineering9060250 - 10 Jun 2022

Cited by 19 | Viewed by 5957

Abstract

Bone defects and complex fractures present significant challenges for orthopaedic surgeons. Current surgical procedures involve the reconstruction and mechanical stabilisation of complex fractures using metal hardware (i.e., wires, plates and screws). However, these procedures often result in poor healing. An injectable, biocompatible, biodegradable [...] Read more.

Bone defects and complex fractures present significant challenges for orthopaedic surgeons. Current surgical procedures involve the reconstruction and mechanical stabilisation of complex fractures using metal hardware (i.e., wires, plates and screws). However, these procedures often result in poor healing. An injectable, biocompatible, biodegradable bone adhesive that could glue bone fragments back together would present a highly attractive solution. A bone adhesive that meets the many clinical requirements for such an application has yet to be developed. While synthetic and biological polymer-based adhesives (e.g., cyanoacrylates, PMMA, fibrin, etc.) have been used effectively as bone void fillers, these materials lack biomechanical integrity and demonstrate poor injectability, which limits the clinical effectiveness and potential for minimally invasive delivery. This systematic review summarises conventional approaches and recent developments in the area of bone adhesives for orthopaedic applications. The required properties for successful bone repair adhesives, which include suitable injectability, setting characteristics, mechanical properties, biocompatibility and an ability to promote new bone formation, are highlighted. Finally, the potential to achieve repair of challenging bone voids and fractures as well as the potential of new bioinspired adhesives and the future directions relating to their clinical development are discussed. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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20 pages, 2321 KiB

Open AccessReview

Biodegradable Magnesium Biomaterials—Road to the Clinic

by Shukufe Amukarimi and Masoud Mozafari

Bioengineering 2022, 9(3), 107; https://doi.org/10.3390/bioengineering9030107 - 5 Mar 2022

Cited by 43 | Viewed by 5929

Abstract

In recent decades, we have witnessed radical changes in the use of permanent biomaterials. The intrinsic ability of magnesium (Mg) and its alloys to degrade without releasing toxic degradation products has led to a vast range of applications in the biomedical field, including [...] Read more.

In recent decades, we have witnessed radical changes in the use of permanent biomaterials. The intrinsic ability of magnesium (Mg) and its alloys to degrade without releasing toxic degradation products has led to a vast range of applications in the biomedical field, including cardiovascular stents, musculoskeletal, and orthopedic applications. With the use of biodegradable Mg biomaterials, patients would not suffer second surgery and surgical pain anymore. Be that as it may, the main drawbacks of these biomaterials are the high corrosion rate and unexpected degradation in physiological environments. Since biodegradable Mg-based implants are expected to show controllable degradation and match the requirements of specific applications, various techniques, such as designing a magnesium alloy and modifying the surface characteristics, are employed to tailor the degradation rate. In this paper, some fundamentals and particular aspects of magnesium degradation in physiological environments are summarized, and approaches to control the degradation behavior of Mg-based biomaterials are presented. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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20 pages, 1129 KiB

Open AccessEditor’s ChoiceReview

Lumbar Intervertebral Disc Herniation: Annular Closure Devices and Key Design Requirements

by Alexandra Alcántara Guardado, Alexander Baker, Andrew Weightman, Judith A. Hoyland and Glen Cooper

Bioengineering 2022, 9(2), 47; https://doi.org/10.3390/bioengineering9020047 - 19 Jan 2022

Cited by 12 | Viewed by 9506

Abstract

Lumbar disc herniation is one of the most common degenerative spinal conditions resulting in lower back pain and sciatica. Surgical treatment options include microdiscectomy, lumbar fusion, total disc replacement, and other minimally invasive approaches. At present, microdiscectomy procedures are the most used technique; [...] Read more.

Lumbar disc herniation is one of the most common degenerative spinal conditions resulting in lower back pain and sciatica. Surgical treatment options include microdiscectomy, lumbar fusion, total disc replacement, and other minimally invasive approaches. At present, microdiscectomy procedures are the most used technique; however, the annulus fibrosus is left with a defect that without treatment may contribute to high reherniation rates and changes in the biomechanics of the lumbar spine. This paper aims to review current commercially available products that mechanically close the annulus including the AnchorKnot^® suture-passing device and the Barricaid^® annular closure device. Previous studies and reviews have focused mainly on a biomimetic biomaterials approach and have described some mechanical and biological requirements for an active annular repair/regeneration strategy but are still far away from clinical implementation. Therefore, in this paper we aim to create a design specification for a mechanical annular closure strategy by identifying the most important mechanical and biological design parameters, including consideration of material selection, preclinical testing requirements, and requirements for clinical implementation. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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27 pages, 1780 KiB

Open AccessReview

Tissue Engineering Strategies for Treating Avascular Necrosis of the Femoral Head

by Sumit Murab, Teresa Hawk, Alexander Snyder, Sydney Herold, Meghana Totapally and Patrick W. Whitlock

Bioengineering 2021, 8(12), 200; https://doi.org/10.3390/bioengineering8120200 - 2 Dec 2021

Cited by 13 | Viewed by 11852

Abstract

Avascular necrosis (AVN) of the femoral head commonly leads to symptomatic osteoarthritis of the hip. In older patients, hip replacement is a viable option that restores the hip biomechanics and improves pain but in pediatric, adolescent, and young adult patients hip replacements impose [...] Read more.

Avascular necrosis (AVN) of the femoral head commonly leads to symptomatic osteoarthritis of the hip. In older patients, hip replacement is a viable option that restores the hip biomechanics and improves pain but in pediatric, adolescent, and young adult patients hip replacements impose significant activity limitations and the need for multiple revision surgeries with increasing risk of complication. Early detection of AVN requires a high level of suspicion as diagnostic techniques such as X-rays are not sensitive in the early stages of the disease. There are multiple etiologies that can lead to this disease. In the pediatric and adolescent population, trauma is a commonly recognized cause of AVN. The understanding of the pathophysiology of the disease is limited, adding to the challenge of devising a clinically effective treatment strategy. Surgical techniques to prevent progression of the disease and avoid total hip replacement include core decompression, vascular grafts, and use of bone-marrow derived stem cells with or without adjuncts, such as bisphosphonates and bone morphogenetic protein (BMP), all of which are partially effective only in the very early stages of the disease. Further, these strategies often only improve pain and range of motion in the short-term in some patients and do not predictably prevent progression of the disease. Tissue engineering strategies with the combined use of biomaterials, stem cells and growth factors offer a potential strategy to avoid metallic implants and surgery. Structural, bioactive biomaterial platforms could help in stabilizing the femoral head while inducing osteogenic differentiation to regenerate bone and provide angiogenic cues to concomitantly recover vasculature in the femoral head. Moreover, injectable systems that can be delivered using a minimal invasive procedure and provide mechanical support the collapsing femoral head could potentially alleviate the need for surgical interventions in the future. The present review describes the limitations of existing surgical methods and the recent advances in tissue engineering that are leading in the direction of a clinically effective, translational solution for AVN in future. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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Bioactive Scaffolds Integrated with Liposomal or Extracellular Vesicles for Bone Regeneration

by Minjee Kang, Chung-Sung Lee and Min Lee

Bioengineering 2021, 8(10), 137; https://doi.org/10.3390/bioengineering8100137 - 1 Oct 2021

Cited by 43 | Viewed by 7459

Abstract

With population aging and increased life expectancy, an increasing number of people are facing musculoskeletal health problems that necessitate therapeutic intervention at defect sites. Bone tissue engineering (BTE) has become a promising approach for bone graft substitutes as traditional treatments using autografts or [...] Read more.

With population aging and increased life expectancy, an increasing number of people are facing musculoskeletal health problems that necessitate therapeutic intervention at defect sites. Bone tissue engineering (BTE) has become a promising approach for bone graft substitutes as traditional treatments using autografts or allografts involve clinical complications. Significant advancements have been made in developing ideal BTE scaffolds that can integrate bioactive molecules promoting robust bone repair. Herein, we review bioactive scaffolds tuned for local bone regenerative therapy, particularly through integrating synthetic liposomal vesicles or extracellular vesicles to the scaffolds. Liposomes offer an excellent drug delivery system providing sustained release of the loaded bioactive molecules. Extracellular vesicles, with their inherent capacity to carry bioactive molecules, are emerging as an advanced substitute of synthetic nanoparticles and a novel cell-free therapy for bone regeneration. We discuss the recent advance in the use of synthetic liposomes and extracellular vesicles as bioactive materials combined with scaffolds, highlighting major challenges and opportunities for their applications in bone regeneration. We put a particular focus on strategies to integrate vesicles to various biomaterial scaffolds and introduce the latest advances in achieving sustained release of bioactive molecules from the vesicle-loaded scaffolds at the bone defect site. Full article

(This article belongs to the Special Issue Multifunctional Scaffolds for Musculoskeletal Regeneration)

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