Special Issue "Biomaterial Enhanced Regeneration"

A special issue of Journal of Functional Biomaterials (ISSN 2079-4983).

Deadline for manuscript submissions: closed (31 July 2018)

Special Issue Editor

Guest Editor
Dr. Dale Feldman

Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
Website | E-Mail
Interests: biomaterials enhanced regeneration; tissue engineering; wound healing enhancement and characterization; tissue state and wound healing assessment; degradable polymers for drug delivery systems and tissue scaffolds

Special Issue Information

This particular issue is devoted to the use of biomaterials to stimulate regeneration or a more regenerative response. This can relate to how biomaterials can be used to enhance the regenerative process, or which methods enhance regeneration that benefit from the presence of the biomaterial.

Biomaterial enhanced regeneration falls under the broad heading of tissue engineering: the use of materials (synthetic and natural) usually in conjunction with cells (both native and genetically modified, as well as stem cells) and/or biological response modifiers (growth factors and cytokines, as well as other stimuli which alter cellular activity). The goal is to use these systems to replace tissue and organ functions (biochemical and/or structural).

Biomaterial enhanced regeneration is the branch of tissue engineering as it relates to biomaterials. This is the designing of materials to better deliver and protect the cells (also potentially guide the differentiation of stem cells) and biological response modifiers as well as, in many cases, to better serve as scaffolds to help promote the healing and regenerative process.

Enhancing regeneration covers both moving more toward regeneration, but also speeding up the process. Typically the step that hinders regeneration is angiogenesis (ingrowth of blood supply in a scaffold) to provide short and long-term viability of the tissue, as well as a high enough oxygen level for fibroblasts to produce extracellular matrix (actual tissue ingrowth).

The presence of a scaffold reduces the healing time by reducing the need for the fibroblasts to produce a scaffold along which it can migrate. The scaffold geometry can be optimized for both fibroblast and blood vessel ingrowth. The surface texture and chemistry can also be modified to enhance this response. The scaffold is also important to best utilize biological response modifiers that stimulate mitosis or migration, which would have a limited effect without a scaffold for the cells to attach to and move along.

Dr. Dale Feldman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Functional Biomaterials is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 850 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Tissue engineering scaffolds
  • Cell–matrix interactions
  • Cell-seeded scaffolds
  • Degradable–regenerative scaffolds
  • Angiogenic or vasculogenic scaffolds
  • Growth factor drug delivery systems
  • Biomimetic extra cellular matrix

Published Papers (8 papers)

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Research

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Open AccessArticle
Influence of Poly(Ethylene Glycol) End Groups on Poly(Ethylene Glycol)-Albumin System Properties as a Potential Degradable Tissue Scaffold
J. Funct. Biomater. 2019, 10(1), 1; https://doi.org/10.3390/jfb10010001
Received: 28 September 2018 / Revised: 28 November 2018 / Accepted: 10 December 2018 / Published: 24 December 2018
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Abstract
Chronic dermal lesions, such as pressure ulcers, are difficult to heal. Degradable tissue scaffold systems can be employed to serve as a provisional matrix for cellular ingrowth and facilitate regenerative healing during degradation. Degradable regenerative tissue scaffold matrices can be created by crosslinking [...] Read more.
Chronic dermal lesions, such as pressure ulcers, are difficult to heal. Degradable tissue scaffold systems can be employed to serve as a provisional matrix for cellular ingrowth and facilitate regenerative healing during degradation. Degradable regenerative tissue scaffold matrices can be created by crosslinking albumin with functionalized poly(ethylene glycol) (PEG) polymers. The purpose of this study was to evaluate the stability of PEG-albumin scaffold systems formed using PEG polymers with three different functionalized end chemistries by quantifying in vitro system swellability to determine the most promising PEG crosslinking polymer for wound healing applications. Of the three polymers evaluated, PEG-succinimidyl glutarate (SG) exhibited consistent gelation and handling characteristics when used as the crosslinking agent with albumin. PEG-SG polymers were identified as an appropriate synthetic crosslinking moiety in a PEG-albumin scaffold system, and further in vitro and in vivo evaluation of this scaffold system is merited. Full article
(This article belongs to the Special Issue Biomaterial Enhanced Regeneration)
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Open AccessFeature PaperArticle
Fibrin as a Tissue Adhesive and Scaffold with an Angiogenic Agent (FGF-1) to Enhance Burn Graft Healing In Vivo and Clinically
J. Funct. Biomater. 2018, 9(4), 68; https://doi.org/10.3390/jfb9040068
Received: 21 September 2018 / Revised: 2 November 2018 / Accepted: 12 November 2018 / Published: 26 November 2018
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Abstract
There is a need for a strategy to reduce scarring in meshed skin graft healing leading to a better cosmetic result without a significant increase in cost. The strategy in this paper is to increase the closure rate of a meshed skin graft [...] Read more.
There is a need for a strategy to reduce scarring in meshed skin graft healing leading to a better cosmetic result without a significant increase in cost. The strategy in this paper is to increase the closure rate of a meshed skin graft to reduce scarring, which should also decrease the infection rate. Specifically, we used fibrin glue to attach all parts of the graft to the wound bed and added in an angiogenic growth factor and made the fibrin porous to further help the growth of blood vessels from the wound bed into the graft. There was a 10-day animal study and a one-month clinical study. Neither making the fibrin porous or adding an angiogenic agent (i.e., fibroblast growth factor-1 (FGF-1)) seemed to make a significant improvement in vivo or clinically. The use of fibrin on a meshed skin graft appears to speed up the regenerative healing rate leading to less scarring in the holes in the mesh. It appears to shorten the healing time by five days and keep the tissue stiffness close to normal levels vs. the doubling of the stiffness by the controls. A larger clinical study, however, is needed to definitively prove this benefit as well as the mechanism for this improvement. Full article
(This article belongs to the Special Issue Biomaterial Enhanced Regeneration)
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Open AccessArticle
The Feasibility of Using Pulsatile Electromagnetic Fields (PEMFs) to Enhance the Regenerative Ability of Dermal Biomaterial Scaffolds
J. Funct. Biomater. 2018, 9(4), 66; https://doi.org/10.3390/jfb9040066
Received: 6 August 2018 / Revised: 28 October 2018 / Accepted: 28 October 2018 / Published: 19 November 2018
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Abstract
Degradable regenerative scaffolds usually require adjunctive treatment to meet the clinical healing performance requirements. This study was designed to look at pulsatile electromagnetic fields (PEMF) as an adjunctive therapy for these scaffolds in skin wounds; however, no scaffold was used in this study [...] Read more.
Degradable regenerative scaffolds usually require adjunctive treatment to meet the clinical healing performance requirements. This study was designed to look at pulsatile electromagnetic fields (PEMF) as an adjunctive therapy for these scaffolds in skin wounds; however, no scaffold was used in this study in order to isolate the effects of PEMF alone. In this study, New Zealand rabbits received four full-thickness defects with a size of 3 cm × 3 cm on the dorsolateral aspect. The rabbits in the treatment group were placed in a chamber and subjected to a PEMF at six different predetermined frequency and intensity combinations for 2 h a day for a 2-week period. At the end of the 2-week period, the animals were sacrificed and tissue samples were taken. Half of each tissue sample was used for histomorphometric analysis and the other half was for tensile testing. The study showed an increased healing response by all the PEMF treatments compared to that in the control, although different combinations led to increases in different aspects of the healing response. This suggests that although some treatments are better for the critical clinical parameter—healing rate, it might be beneficial to use treatments in the early stages to increase angiogenesis before the treatment is switched to the one best for the healing rate to get an even better haling rate. Full article
(This article belongs to the Special Issue Biomaterial Enhanced Regeneration)
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Open AccessArticle
Mesenchymal Stem Cells and Transforming Growth Factor-β3 (TGF-β3) to Enhance the Regenerative Ability of an Albumin Scaffold in Full Thickness Wound Healing
J. Funct. Biomater. 2018, 9(4), 65; https://doi.org/10.3390/jfb9040065
Received: 27 September 2018 / Revised: 25 October 2018 / Accepted: 1 November 2018 / Published: 14 November 2018
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Abstract
Pressure ulcers are one of the most common forms of skin injury, particularly in the spinal cord injured (SCI). Pressure ulcers are difficult to heal in this population requiring at least six months of bed rest. Surgical treatment (grafting) is the fastest recovery [...] Read more.
Pressure ulcers are one of the most common forms of skin injury, particularly in the spinal cord injured (SCI). Pressure ulcers are difficult to heal in this population requiring at least six months of bed rest. Surgical treatment (grafting) is the fastest recovery time, but it still requires six weeks of bed rest plus significant additional costs and a high recurrence rate. A significant clinical benefit would be obtained by speeding the healing rate of a non-surgical treatment to close to that of surgical treatment (approximately doubling of healing rate). Current non-surgical treatment is mostly inactive wound coverings. The goal of this project was to look at the feasibility of doubling the healing rate of a full-thickness defect using combinations of three treatments, for the first time, each shown to increase healing rate: application of transforming growth factor-β3 (TGF-β3), an albumin based scaffold, and mesenchymal stem cells (MSCs). At one week following surgery, the combined treatment showed the greatest increase in healing rate, particularly for the epithelialization rate. Although the target level of a 100% increase in healing rate over the control was not quite achieved, it is anticipated that the goal would be met with further optimization of the treatment. Full article
(This article belongs to the Special Issue Biomaterial Enhanced Regeneration)
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Open AccessArticle
Transcatheter Decellularized Tissue-Engineered Heart Valve (dTEHV) Grown on Polyglycolic Acid (PGA) Scaffold Coated with P4HB Shows Improved Functionality over 52 Weeks due to Polyether-Ether-Ketone (PEEK) Insert
J. Funct. Biomater. 2018, 9(4), 64; https://doi.org/10.3390/jfb9040064
Received: 31 July 2018 / Revised: 26 August 2018 / Accepted: 10 September 2018 / Published: 13 November 2018
Cited by 2 | PDF Full-text (8392 KB) | HTML Full-text | XML Full-textRetraction
Abstract
Many congenital heart defects and degenerative valve diseases require replacement of heart valves in children and young adults. Transcatheter xenografts degenerate over time. Tissue engineering might help to overcome this limitation by providing valves with ability for self-repair. A transcatheter decellularized tissue-engineered heart [...] Read more.
Many congenital heart defects and degenerative valve diseases require replacement of heart valves in children and young adults. Transcatheter xenografts degenerate over time. Tissue engineering might help to overcome this limitation by providing valves with ability for self-repair. A transcatheter decellularized tissue-engineered heart valve (dTEHV) was developed using a polyglycolic acid (PGA) scaffold. A first prototype showed progressive regurgitation after 6 months in-vivo due to a suboptimal design and misguided remodeling process. A new geometry was developed accordingly with computational fluid dynamics (CFD) simulations and implemented by adding a polyether-ether-ketone (PEEK) insert to the bioreactor during cultivation. This lead to more belly-shaped leaflets with higher coaptation areas for this second generation dTEHV. Valve functionality assessed via angiography, intracardiac echocardiography, and MRI proved to be much better when compared the first generation dTEHV, with preserved functionality up to 52 weeks after implantation. Macroscopic findings showed no thrombi or signs of acute inflammation. For the second generation dTEHV, belly-shaped leaflets with soft and agile tissue-formation were seen after explantation. No excessive leaflet shortening occurred in the second generation dTEHV. Histological analysis showed complete engraftment of the dTEHV, with endothelialization of the leaflets and the graft wall. Leaflets consisted of collagenous tissue and some elastic fibers. Adaptive leaflet remodeling was visible in all implanted second generation dTEHV, and most importantly no fusion between leaflet and wall was found. Very few remnants of the PGA scaffold were detected even 52 weeks after implantation, with no influence on functionality. By adding a polyether-ether-ketone (PEEK) insert to the bioreactor construct, a new geometry of PGA-scaffold based dTEHV could be implemented. This resulted in very good valve function of the implanted dTEHV over a period of 52 weeks. Full article
(This article belongs to the Special Issue Biomaterial Enhanced Regeneration)
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Open AccessArticle
Evaluation of Antibiotic-Releasing Triphasic Bone Void Filler In-Vitro
J. Funct. Biomater. 2018, 9(4), 55; https://doi.org/10.3390/jfb9040055
Received: 31 July 2018 / Revised: 31 August 2018 / Accepted: 17 September 2018 / Published: 21 September 2018
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Abstract
Bone void fillers (BVFs) containing calcium sulfate, tricalcium phosphate (TCP), and hydroxyapatite can be loaded with antibiotics for infection treatment or prevention under surgeon-directed use. The aim of this study was to characterize the handling and elution properties of a triphasic BVF loaded [...] Read more.
Bone void fillers (BVFs) containing calcium sulfate, tricalcium phosphate (TCP), and hydroxyapatite can be loaded with antibiotics for infection treatment or prevention under surgeon-directed use. The aim of this study was to characterize the handling and elution properties of a triphasic BVF loaded with common antibiotics. BVF was mixed with vancomycin and/or tobramycin to form pellets, and the set time was recorded. A partial refreshment elution study was conducted with time points at 4, 8, and 24 h, as well as 2, 7, 14, 28, and 42 days. Effects on dissolution were evaluated in a 14-day dissolution study. Set time increased to over 1 h for groups containing tobramycin, although vancomycin had a minimal effect. Pellets continued to elute antibiotics throughout the 42-day elution study, suggesting efficacy for the treatment or prevention of orthopedic infections. BVF containing vancomycin or tobramycin showed similar dissolution at 14 days compared to BVF without antibiotics; however, BVF containing both antibiotics showed significantly more dissolution. Full article
(This article belongs to the Special Issue Biomaterial Enhanced Regeneration)
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Open AccessArticle
Specialized Living Wound Dressing Based on the Self-Assembly Approach of Tissue Engineering
J. Funct. Biomater. 2018, 9(3), 53; https://doi.org/10.3390/jfb9030053
Received: 31 July 2018 / Revised: 30 August 2018 / Accepted: 10 September 2018 / Published: 15 September 2018
Cited by 1 | PDF Full-text (2861 KB) | HTML Full-text | XML Full-text
Abstract
There is a high incidence of failure and recurrence for chronic skin wounds following conventional therapies. To promote healing, the use of skin substitutes containing living cells as wound dressings has been proposed. The aim of this study was to produce a scaffold-free [...] Read more.
There is a high incidence of failure and recurrence for chronic skin wounds following conventional therapies. To promote healing, the use of skin substitutes containing living cells as wound dressings has been proposed. The aim of this study was to produce a scaffold-free cell-based bilayered tissue-engineered skin substitute (TES) containing living fibroblasts and keratinocytes suitable for use as wound dressing, while considering production time, handling effort during the manufacturing process, and stability of the final product. The self-assembly method, which relies on the ability of mesenchymal cells to secrete and organize connective tissue sheet sustaining keratinocyte growth, was used to produce TESs. Three fibroblast-seeding densities were tested to produce tissue sheets. At day 17, keratinocytes were added onto 1 or 3 (reference method) stacked tissue sheets. Four days later, TESs were subjected either to 4, 10, or 17 days of culture at the air–liquid interface (A/L). All resulting TESs were comparable in terms of their histological aspect, protein expression profile and contractile behavior in vitro. However, signs of extracellular matrix (ECM) digestion that progressed over culture time were noted in TESs produced with only one fibroblast-derived tissue sheet. With lower fibroblast density, the ECM of TESs was almost completely digested after 10 days A/L and lost histological integrity after grafting in athymic mice. Increasing the fibroblast seeding density 5 to 10 times solved this problem. We conclude that the proposed method allows for a 25-day production of a living TES, which retains its histological characteristics in vitro for at least two weeks. Full article
(This article belongs to the Special Issue Biomaterial Enhanced Regeneration)
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Review

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Open AccessFeature PaperReview
Biomaterial Enhanced Regeneration Design Research for Skin and Load Bearing Applications
J. Funct. Biomater. 2019, 10(1), 10; https://doi.org/10.3390/jfb10010010
Received: 18 December 2018 / Revised: 11 January 2019 / Accepted: 15 January 2019 / Published: 26 January 2019
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Abstract
Biomaterial enhanced regeneration (BER) falls mostly under the broad heading of Tissue Engineering: the use of materials (synthetic and natural) usually in conjunction with cells (both native and genetically modified as well as stem cells) and/or biological response modifiers (growth factors and cytokines [...] Read more.
Biomaterial enhanced regeneration (BER) falls mostly under the broad heading of Tissue Engineering: the use of materials (synthetic and natural) usually in conjunction with cells (both native and genetically modified as well as stem cells) and/or biological response modifiers (growth factors and cytokines as well as other stimuli, which alter cellular activity). Although the emphasis is on the biomaterial as a scaffold it is also the use of additive bioactivity to enhance the healing and regenerative properties of the scaffold. Enhancing regeneration is both moving more toward regeneration but also speeding up the process. The review covers principles of design for BER as well as strategies to select the best designs. This is first general design principles, followed by types of design options, and then specific strategies for applications in skin and load bearing applications. The last section, surveys current clinical practice (for skin and load bearing applications) including limitations of these approaches. This is followed by future directions with an attempt to prioritize strategies. Although the review is geared toward design optimization, prioritization also includes the commercializability of the devices. This means a device must meet both the clinical performance design constraints as well as the commercializability design constraints. Full article
(This article belongs to the Special Issue Biomaterial Enhanced Regeneration)
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