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Article ; Online: Biological Processes in Gingival Tissue Integration Around Dental Implants.

Han, Jing / Leeuwenburgh, Sander C G / Jansen, John A / Yang, Fang / van Oirschot, Bart A J A

2024

Language	English
Publishing date	2024-04-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2420584-9
ISSN	1937-3376 ; 1937-3368
ISSN (online)	1937-3376
ISSN	1937-3368
DOI	10.1089/ten.TEB.2023.0371
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Article ; Online: Self-Healing Injectable Hydrogels for Tissue Regeneration.

Bertsch, Pascal / Diba, Mani / Mooney, David J / Leeuwenburgh, Sander C G

Chemical reviews

2022 Volume 123, Issue 2, Page(s) 834–873

Abstract: Biomaterials with the ability to self-heal and recover their structural integrity offer many advantages for applications in biomedicine. The past decade has witnessed the rapid emergence of a new class of self-healing biomaterials commonly termed ... ...

Abstract	Biomaterials with the ability to self-heal and recover their structural integrity offer many advantages for applications in biomedicine. The past decade has witnessed the rapid emergence of a new class of self-healing biomaterials commonly termed injectable, or printable in the context of 3D printing. These self-healing injectable biomaterials, mostly hydrogels and other soft condensed matter based on reversible chemistry, are able to temporarily fluidize under shear stress and subsequently recover their original mechanical properties. Self-healing injectable hydrogels offer distinct advantages compared to traditional biomaterials. Most notably, they can be administered in a locally targeted and minimally invasive manner through a narrow syringe without the need for invasive surgery. Their moldability allows for a patient-specific intervention and shows great prospects for personalized medicine. Injected hydrogels can facilitate tissue regeneration in multiple ways owing to their viscoelastic and diffusive nature, ranging from simple mechanical support, spatiotemporally controlled delivery of cells or therapeutics, to local recruitment and modulation of host cells to promote tissue regeneration. Consequently, self-healing injectable hydrogels have been at the forefront of many cutting-edge tissue regeneration strategies. This study provides a critical review of the current state of self-healing injectable hydrogels for tissue regeneration. As key challenges toward further maturation of this exciting research field, we identify (i) the trade-off between the self-healing and injectability of hydrogels vs their physical stability, (ii) the lack of consensus on rheological characterization and quantitative benchmarks for self-healing injectable hydrogels, particularly regarding the capillary flow in syringes, and (iii) practical limitations regarding translation toward therapeutically effective formulations for regeneration of specific tissues. Hence, here we (i) review chemical and physical design strategies for self-healing injectable hydrogels, (ii) provide a practical guide for their rheological analysis, and (iii) showcase their applicability for regeneration of various tissues and 3D printing of complex tissues and organoids.
MeSH term(s)	Humans ; Hydrogels/chemistry ; Biocompatible Materials/pharmacology ; Biocompatible Materials/chemistry ; Tissue Engineering
Chemical Substances	Hydrogels ; Biocompatible Materials
Language	English
Publishing date	2022-08-05
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	207949-5
ISSN	1520-6890 ; 0009-2665
ISSN (online)	1520-6890
ISSN	0009-2665
DOI	10.1021/acs.chemrev.2c00179
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Article ; Online: Calcium Phosphate and Silicate-Based Nanoparticles: History and Emerging Trends.

van Rijt, Sabine / de Groot, Klaas / Leeuwenburgh, Sander C G

Tissue engineering. Part A

2022 Volume 28, Issue 11-12, Page(s) 461–477

Abstract: Calcium phosphates (CaPs) and silicate-based bioglasses have been extensively studied since the early 1970s due to their unique capacity to bind to host bone, which led to their clinical translation and commercialization in the 1980s. Since the mid-1990s, ...

Abstract	Calcium phosphates (CaPs) and silicate-based bioglasses have been extensively studied since the early 1970s due to their unique capacity to bind to host bone, which led to their clinical translation and commercialization in the 1980s. Since the mid-1990s, researchers have synthesized nanoscale CaP and silicate-based particles of increased specific surface area, chemical reactivity, and solubility, which offer specific advantages compared to their bulk counterparts. This review provides a critical perspective on the history and emerging trends of these two classes of ceramic nanoparticles. Their synthesis and functional properties in terms of particle composition, size, shape, charge, dispersion, and toxicity are discussed as a function of relevant processing parameters. Specifically, emerging trends such as the influence of ion doping and mesoporosity on the biological and pharmaceutical performance of these nanoparticles are reviewed in more detail. Finally, a broad comparative overview is provided on the physicochemical properties and applicability of CaP and silicate-based nanoparticles within the fields of (i) local delivery of therapeutic agents, (ii) functionalization of biomaterial scaffolds or implant coatings, and (iii) bioimaging applications. Impact statement This review provides a critical perspective on the history and emerging trends of the two main classes of bioceramic nanoparticles, that is, calcium phosphate (CaP) and silicate-based nanoparticles. While most reviews in literature focus on either CaP or silicate-based nanoparticles, our review evaluates both classes of bioceramic nanoparticles simultaneously. This combined review offers the opportunity to analyze differences and similarities with respect to the historic development and emerging trends within both fields of bioceramics research.
MeSH term(s)	Biocompatible Materials ; Calcium Phosphates/chemistry ; Nanoparticles/chemistry ; Silicates/chemistry
Chemical Substances	Biocompatible Materials ; Calcium Phosphates ; Silicates ; calcium phosphate (97Z1WI3NDX)
Language	English
Publishing date	2022-05-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2420582-5
ISSN	1937-335X ; 1937-3341
ISSN (online)	1937-335X
ISSN	1937-3341
DOI	10.1089/ten.TEA.2021.0218
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Article ; Online: The Use of Fibers in Bone Tissue Engineering.

Petre, Daniela Geta / Leeuwenburgh, Sander C G

Tissue engineering. Part B, Reviews

2021 Volume 28, Issue 1, Page(s) 141–159

Abstract: Bone tissue engineering aims to restore and maintain the function of bone by means of biomaterial-based scaffolds. This review specifically focuses on the use of fibers in biomaterials used for bone tissue engineering as suitable environment for bone ... ...

Abstract	Bone tissue engineering aims to restore and maintain the function of bone by means of biomaterial-based scaffolds. This review specifically focuses on the use of fibers in biomaterials used for bone tissue engineering as suitable environment for bone tissue repair and regeneration. We present a bioinspired rationale behind the use of fibers in bone tissue engineering and provide an overview of the most common fiber fabrication methods, including solution, melt, and microfluidic spinning. Subsequently, we provide a brief overview of the composition of fibers that are used in bone tissue engineering, including fibers composed of (i) natural polymers (e.g., cellulose, collagen, gelatin, alginate, chitosan, and silk, (ii) synthetic polymers (e.g., polylactic acid [PLA], polycaprolactone, polyglycolic acid [PGA], polyethylene glycol, and polymer blends of PLA and PGA), (iii) ceramic fibers (e.g., aluminium oxide, titanium oxide, and zinc oxide), (iv) metallic fibers (e.g., titanium and its alloys, copper and magnesium), and (v) composite fibers. In addition, we review the most relevant fiber modification strategies that are used to enhance the (bio)functionality of these fibers. Finally, we provide an overview of the applicability of fibers in biomaterials for bone tissue engineering, with a specific focus on mechanical, pharmaceutical, and biological properties of fiber-functionalized biomaterials for bone tissue engineering. Impact statement Natural bone is a complex composite material composed of an extracellular matrix of mineralized fibers containing living cells and bioactive molecules. Consequently, the use of fibers in biomaterial-based scaffolds offers a wide variety of opportunities to replicate the functional performance of bone. This review provides an overview of the use of fibers in biomaterials for bone tissue engineering, thereby contributing to the design of novel fiber-functionalized bone-substituting biomaterials of improved functionality regarding their mechanical, pharmaceutical, and biological properties.
MeSH term(s)	Biocompatible Materials ; Bone and Bones ; Collagen ; Tissue Engineering/methods ; Tissue Scaffolds
Chemical Substances	Biocompatible Materials ; Collagen (9007-34-5)
Language	English
Publishing date	2021-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2420584-9
ISSN	1937-3376 ; 1937-3368
ISSN (online)	1937-3376
ISSN	1937-3368
DOI	10.1089/ten.TEB.2020.0252
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Article ; Online: Bone adhesive materials: From bench to bedside.

Bingol, Hatice B / Bender, Johan C M E / Opsteen, Joost A / Leeuwenburgh, Sander C G

Materials today. Bio

2023 Volume 19, Page(s) 100599

Abstract: Biodegradable bone adhesives represent a highly sought-after type of biomaterial which would enable replacement of traditional metallic devices for fixation of bone. However, these biomaterials should fulfil an extremely large number of requirements. As ... ...

Abstract	Biodegradable bone adhesives represent a highly sought-after type of biomaterial which would enable replacement of traditional metallic devices for fixation of bone. However, these biomaterials should fulfil an extremely large number of requirements. As a consequence, bone-adhesive biomaterials which meet all of these requirements are not yet commercially available. Therefore, this comprehensive review provides an extensive overview of the development of bone adhesives from a translational perspective. First, the definition, classification, and chemistry of various types of bone adhesives are highlighted to provide a detailed overview of this emerging class of biomaterials. In this review we particularly focused studies which describe the use of materials that are capable of gluing two pieces of bone together within a time frame of minutes to days. Second, this review critically reflects on i) the experimental conditions of commonly employed adhesion tests to assess bone adhesion and ii) the current state-of-the-art regarding their preclinical and clinical applicability.
Language	English
Publishing date	2023-03-02
Publishing country	England
Document type	Journal Article ; Review
ISSN	2590-0064
ISSN (online)	2590-0064
DOI	10.1016/j.mtbio.2023.100599
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Article ; Online: Biofunctionalization of dental abutments by a zinc/chitosan/gelatin coating to optimize fibroblast behavior and antibacterial properties.

Han, Jing / Andrée, Lea / Deng, Dongmei / van Oirschot, Bart A J A / Plachokova, Adelina S / Leeuwenburgh, Sander C G / Yang, Fang

Journal of biomedical materials research. Part A

2024

Abstract: Tightly sealed peri-implant gingival tissue provides a barrier against oral bacterial invasion, protecting the alveolar bone and maintaining long-term implant survival. To investigate if zinc can enhance the integration between peri-implant gingival ... ...

Abstract	Tightly sealed peri-implant gingival tissue provides a barrier against oral bacterial invasion, protecting the alveolar bone and maintaining long-term implant survival. To investigate if zinc can enhance the integration between peri-implant gingival tissue and abutment surface, we herein present novel zinc/chitosan/gelatin (Zn/CS/Gel) coatings prepared using the electrophoretic deposition (EPD) technique. The effect of these coatings on human gingival fibroblasts (hGFs) was investigated by culturing these cells on top of the EPD coatings. Surface characterization demonstrated that Zn
Language	English
Publishing date	2024-05-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2099989-6
ISSN	1552-4965 ; 1549-3296 ; 0021-9304
ISSN (online)	1552-4965
ISSN	1549-3296 ; 0021-9304
DOI	10.1002/jbm.a.37734
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Article ; Online: Encapsulation of pristine and silica-coated human adipose-derived mesenchymal stem cells in gelatin colloidal hydrogels for tissue engineering and bioprinting applications.

Maciel, Marta M / Hassani Besheli, Negar / Correia, Tiago R / Mano, João F / Leeuwenburgh, Sander C G

Biotechnology journal

2023 Volume 19, Issue 2, Page(s) e2300469

Abstract: Colloidal gels assembled from gelatin nanoparticles (GNPs) as particulate building blocks show strong promise to solve challenges in cell delivery and biofabrication, such as low cell survival and limited spatial retention. These gels offer evident ... ...

Abstract	Colloidal gels assembled from gelatin nanoparticles (GNPs) as particulate building blocks show strong promise to solve challenges in cell delivery and biofabrication, such as low cell survival and limited spatial retention. These gels offer evident advantages to facilitate cell encapsulation, but research on this topic is still limited, which hampers our understanding of the relationship between the physicochemical and biological properties of cell-laden colloidal gels. Human adipose-derived mesenchymal stem cells were successfully encapsulated in gelatin colloidal gels and evaluated their mechanical and biological performance over 7 days. The cells dispersed well within the gels without compromising gel cohesiveness, remained viable, and spread throughout the gels. Cells partially coated with silica were introduced into these gels, which increased their storage moduli and decreased their self-healing capacity after 7 days. This finding demonstrates the ability to modulate gel stiffness by incorporating cells partially coated with silica, without altering the solid content or introducing additional particles. Our work presents an efficient method for cell encapsulation while preserving gel integrity, expanding the applicability of colloidal hydrogels for tissue engineering and bioprinting. Overall, our study contributes to the design of improved cell delivery systems and biofabrication techniques.
MeSH term(s)	Humans ; Hydrogels/chemistry ; Tissue Engineering ; Gelatin/chemistry ; Bioprinting ; Silicon Dioxide ; Mesenchymal Stem Cells ; Tissue Scaffolds/chemistry
Chemical Substances	Hydrogels ; Gelatin (9000-70-8) ; Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2023-12-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2221885-3
ISSN	1860-7314 ; 1860-6768
ISSN (online)	1860-7314
ISSN	1860-6768
DOI	10.1002/biot.202300469
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Article ; Online: Colloidal hydrogels made of gelatin nanoparticles exhibit fast stress relaxation at strains relevant for cell activity.

Bertsch, Pascal / Andrée, Lea / Besheli, Negar Hassani / Leeuwenburgh, Sander C G

Acta biomaterialia

2021 Volume 138, Page(s) 124–132

Abstract: Viscoelastic properties of hydrogels such as stress relaxation or plasticity have been recognized as important mechanical cues that dictate the migration, proliferation, and differentiation of embedded cells. Stress relaxation rates in conventional ... ...

Abstract	Viscoelastic properties of hydrogels such as stress relaxation or plasticity have been recognized as important mechanical cues that dictate the migration, proliferation, and differentiation of embedded cells. Stress relaxation rates in conventional hydrogels are usually much slower than cellular processes, which impedes rapid cellularization of these elastic networks. Colloidal hydrogels assembled from nanoscale building blocks may provide increased degrees of freedom in the design of viscoelastic hydrogels with accelerated stress relaxation rates due to their strain-sensitive rheology which can be tuned via interparticle interactions. Here, we investigate the stress relaxation of colloidal hydrogels from gelatin nanoparticles in comparison to physical gelatin hydrogels and explore the particle interactions that govern stress relaxation. Colloidal and physical gelatin hydrogels exhibit comparable rheology at small deformations, but colloidal hydrogels fluidize beyond a critical strain while physical gels remain primarily elastic independent of strain. This fluidization facilitates fast exponential stress relaxation in colloidal gels at strain levels that correspond to strains exerted by cells embedded in physiological extracellular matrices (10-50%). Increased attractive particle interactions result in a higher critical strain and slower stress relaxation in colloidal gels. In physical gels, stress relaxation is slower and mostly independent of strain. Hence, colloidal hydrogels offer the possibility to modulate viscoelasticity via interparticle interactions and obtain fast stress relaxation rates at strains relevant for cell activity. These beneficial features render colloidal hydrogels promising alternatives to conventional monolithic hydrogels for tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE: In the endeavor to design biomaterials that favor cell activity, research has long focused on biochemical cues. Recently, the time-, stress-, and strain-dependent mechanical properties, i.e. viscoelasticity, of biomaterials has been recognized as important factor that dictates cell fate. We herein present the viscoelastic stress relaxation of colloidal hydrogels assembled from gelatin nanoparticles, which show a strain-dependent fluidization at strains relevant for cell activity, in contrast to many commonly used monolithic hydrogels with primarily elastic behavior.
MeSH term(s)	Biocompatible Materials ; Gelatin ; Hydrogels/pharmacology ; Nanoparticles ; Tissue Engineering
Chemical Substances	Biocompatible Materials ; Hydrogels ; Gelatin (9000-70-8)
Language	English
Publishing date	2021-11-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2021.10.053
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Article ; Online: Unraveling the Formation of Gelatin Nanospheres by Means of Desolvation.

Hassani Besheli, Negar / Martens, Martijn / Macías-Sánchez, Elena / Olijve, Jos / Yang, Fang / Sommerdijk, Nico / Leeuwenburgh, Sander C G

Nano letters

2023 Volume 23, Issue 23, Page(s) 11091–11098

Abstract: Gelatin nanoparticles (GNPs) have been widely studied for a plethora of biomedical applications, but their formation mechanism remains poorly understood, which precludes precise control over their physicochemical properties. This leads to time-consuming ... ...

Abstract	Gelatin nanoparticles (GNPs) have been widely studied for a plethora of biomedical applications, but their formation mechanism remains poorly understood, which precludes precise control over their physicochemical properties. This leads to time-consuming parameter adjustments without a fundamental grasp of the underlying mechanism. Here, we analyze and visualize in a time-resolved manner the mechanism by which GNPs are formed during desolvation of gelatin as a function of gelatin molecular weight and type of desolvating agent. Through various analytical and imaging techniques, we unveil a multistage process that is initiated by the formation of primary particles that are ∼18 nm in diameter (wet state). These primary particles subsequently assemble into colloidally stable GNPs with a raspberry-like structure and a hydrodynamic diameter of ∼300 nm. Our results create a basic understanding of the formation mechanism of gelatin nanoparticles, which opens new opportunities for precisely tuning their physicochemical and biofunctional properties.
Language	English
Publishing date	2023-11-15
Publishing country	United States
Document type	Journal Article
ISSN	1530-6992
ISSN (online)	1530-6992
DOI	10.1021/acs.nanolett.3c03459
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Article ; Online: A Modular Platform for Cytocompatible Hydrogels with Tailored Mechanical Properties Based on Monolithic Matrices and Particulate Building Blocks.

Andrée, Lea / Bertsch, Pascal / Wang, Rong / Becker, Malin / Leijten, Jeroen / Fischer, Peter / Yang, Fang / Leeuwenburgh, Sander C G

Biomacromolecules

2023 Volume 24, Issue 6, Page(s) 2755–2765

Abstract: We establish a versatile hydrogel platform based on modular building blocks that allows the design of hydrogels with tailored physical architecture and mechanical properties. We demonstrate its versatility by assembling (i) a fully monolithic gelatin ... ...

Abstract	We establish a versatile hydrogel platform based on modular building blocks that allows the design of hydrogels with tailored physical architecture and mechanical properties. We demonstrate its versatility by assembling (i) a fully monolithic gelatin methacryloyl (Gel-MA) hydrogel, (ii) a hybrid hydrogel composed of 1:1 Gel-MA and gelatin nanoparticles, and (iii) a fully particulate hydrogel based on methacryloyl-modified gelatin nanoparticles. The hydrogels were formulated to exhibit the same solid content and comparable storage modulus but different stiffness and viscoelastic stress relaxation. The incorporation of particles resulted in softer hydrogels with enhanced stress relaxation. Murine osteoblastic cells cultured in two-dimensional (2D) on hydrogels showed proliferation and metabolic activity comparable to established collagen hydrogels. Furthermore, the osteoblastic cells showed a trend of increased cell numbers, cell expansion, and more defined protrusions on stiffer hydrogels. Hence, modular assembly allows the design of hydrogels with tailored mechanical properties and the potential to alter cell behavior.
MeSH term(s)	Mice ; Animals ; Gelatin ; Hydrogels/pharmacology ; Collagen ; Cell Proliferation ; Tissue Engineering/methods
Chemical Substances	Gelatin (9000-70-8) ; Hydrogels ; Collagen (9007-34-5)
Language	English
Publishing date	2023-05-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.3c00177
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