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Pharmaceutics
Special Issues
Implantable Materials for Drug Delivery in Tissue Regeneration
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Implantable Materials for Drug Delivery in Tissue Regeneration

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (10 November 2023) | Viewed by 16705

Special Issue Editors

Prof. Dr. Mariana Landin

E-Mail Website
Guest Editor
Departamento de Farmacología, Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Interests: drug delivery; pharmaceutical technology; biomedical engineering; Artificial Intelligence
Special Issues, Collections and Topics in MDPI journals
Dr. Patricia Diaz-Rodriguez

E-Mail Website
Guest Editor
Department of Chemical Engineering and Pharmaceutical Technology, School of Science, Universidad de La Laguna, 38204 La Laguna, Spain
Interests: drug delivery; regenerative medicine; biomaterials; biomedical engineering; pharmaceutical technology

Special Issue Information

Dear Colleagues,

The incorporation of new technologies into the field of regenerative medicine over the past few decades has led to the production of new biomaterials tailor-made to fulfill the patient’s needs. Ideally, these biomaterials must be completely degradable under the physiological conditions leading to the repair of the damaged tissue, maintaining the desired structure. The integration of therapeutic molecules into biomaterials can provide extra value to implantable systems. The use of biomaterials loaded with drugs—either for the transfer of drugs in situ or for the promotion of a specific cellular microenvironment—has been suggested as an interesting strategy to treat different pathologies, avoid surgical complications derived from the implantation of materials, and/or promote the regeneration of tissues.

Traditionally, bone has been the most commonly targeted tissue for the development of biomaterials loaded with drugs. However, today, these systems are designed for other applications, such as skin, cartilage, and cardiovascular tissue, among others. The development of these delivery systems and the optimization of existing ones require experience in the fields of both biomaterial engineering and pharmaceutical technology.

This Special Issue aims to identify the current progress in the design, development, and evaluation of implantable materials for drug delivery in tissue regeneration.

Prof. Dr. Mariana Landin
Dr. Patricia Diaz-Rodriguez
Guest Editors

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Keywords

  • local drug delivery
  • drug-loaded biomaterials
  • implantable systems
  • tissue regeneration
  • biomimetic biomaterials
  • drug release profile
  • in vitro testing
  • preclinical studies

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Published Papers (5 papers)

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Research

18 pages, 3267 KiB  
Article
Angiogenic Properties of Concentrated Growth Factors (CGFs): The Role of Soluble Factors and Cellular Components
by Nadia Calabriso, Eleonora Stanca, Alessio Rochira, Fabrizio Damiano, Laura Giannotti, Benedetta Di Chiara Stanca, Marika Massaro, Egeria Scoditti, Christian Demitri, Paola Nitti, Andrea Palermo, Luisa Siculella and Maria Annunziata Carluccio
Pharmaceutics 2021, 13(5), 635; https://doi.org/10.3390/pharmaceutics13050635 - 29 Apr 2021
Cited by 39 | Viewed by 2725
Abstract
Blood-derived concentrated growth factors (CGFs) represent a novel autologous biomaterial with promising applications in regenerative medicine. Angiogenesis is a key factor in tissue regeneration, but the role played by CGFs in vessel formation is not clear. The purpose of this study was to [...] Read more.
Blood-derived concentrated growth factors (CGFs) represent a novel autologous biomaterial with promising applications in regenerative medicine. Angiogenesis is a key factor in tissue regeneration, but the role played by CGFs in vessel formation is not clear. The purpose of this study was to characterize the angiogenic properties of CGFs by evaluating the effects of its soluble factors and cellular components on the neovascularization in an in vitro model of angiogenesis. CGF clots were cultured for 14 days in cell culture medium; after that, CGF-conditioned medium (CGF-CM) was collected, and soluble factors and cellular components were separated and characterized. CGF-soluble factors, such as growth factors (VEGF and TGF-β1) and matrix metalloproteinases (MMP-2 and -9), were assessed by ELISA. Angiogenic properties of CGF-soluble factors were analyzed by stimulating human cultured endothelial cells with increasing concentrations (1%, 5%, 10%, or 20%) of CGF-CM, and their effect on cell migration and tubule-like formation was assessed by wound healing and Matrigel assay, respectively. The expression of endothelial angiogenic mediators was determined using qRT-PCR and ELISA assays. CGF-derived cells were characterized by immunostaining, qRT-PCR and Matrigel assay. We found that CGF-CM, consisting of essential pro-angiogenic factors, such as VEGF, TGF-β1, MMP-9, and MMP-2, promoted endothelial cell migration; tubule structure formation; and endothelial expression of multiple angiogenic mediators, including growth factors, chemokines, and metalloproteinases. Moreover, we discovered that CGF-derived cells exhibited features such as endothelial progenitor cells, since they expressed the CD34 stem cell marker and endothelial markers and participated in the neo-angiogenic process. In conclusion, our results suggest that CGFs are able to promote endothelial angiogenesis through their soluble and cellular components and that CGFs can be used as a biomaterial for therapeutic vasculogenesis in the field of tissue regeneration. Full article
(This article belongs to the Special Issue Implantable Materials for Drug Delivery in Tissue Regeneration)
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27 pages, 9233 KiB  
Article
Sustained Calcium(II)-Release to Impart Bioactivity in Hybrid Glass Scaffolds for Bone Tissue Engineering
by Dzmitry Kuzmenka, Claudia Sewohl, Andreas König, Tobias Flath, Sebastian Hahnel, Fritz Peter Schulze, Michael C. Hacker and Michaela Schulz-Siegmund
Pharmaceutics 2020, 12(12), 1192; https://doi.org/10.3390/pharmaceutics12121192 - 8 Dec 2020
Cited by 12 | Viewed by 2884
Abstract
In this study, we integrated different calcium sources into sol-gel hybrid glass scaffolds with the aim of producing implants with long-lasting calcium release while maintaining mechanical strength of the implant. Calcium(II)-release was used to introduce bioactivity to the material and eventually support implant [...] Read more.
In this study, we integrated different calcium sources into sol-gel hybrid glass scaffolds with the aim of producing implants with long-lasting calcium release while maintaining mechanical strength of the implant. Calcium(II)-release was used to introduce bioactivity to the material and eventually support implant integration into a bone tissue defect. Tetraethyl orthosilicate (TEOS) derived silica sols were cross-linked with an ethoxysilylated 4-armed macromer, pentaerythritol ethoxylate and processed into macroporous scaffolds with defined pore structure by indirect rapid prototyping. Triethyl phosphate (TEP) was shown to function as silica sol solvent. In a first approach, we investigated the integration of 1 to 10% CaCl2 in order to test the hypothesis that small CaCl2 amounts can be physically entrapped and slowly released from hybrid glass scaffolds. With 5 and 10% CaCl2 we observed an extensive burst release, whereas slightly improved release profiles were found for lower Calcium(II) contents. In contrast, introduction of melt-derived bioactive 45S5 glass microparticles (BG-MP) into the hybrid glass scaffolds as another Calcium(II) source led to an approximately linear release of Calcium(II) in Tris(hydroxymethyl)aminomethane (TRIS) buffer over 12 weeks. pH increase caused by BG-MP could be controlled by their amount integrated into the scaffolds. Compression strength remained unchanged compared to scaffolds without BG-MP. In cell culture medium as well as in simulated body fluid, we observed a rapid formation of a carbonated hydroxyapatite layer on BG-MP containing scaffolds. However, this mineral layer consumed the released Calcium(II) ions and prevented an additional increase in Calcium(II) concentration in the cell culture medium. Cell culture studies on the different scaffolds with osteoblast-like SaOS-2 cells as well as bone marrow derived mesenchymal stem cells (hMSC) did not show any advantages concerning osteogenic differentiation due to the integration of BG-MP into the scaffolds. Nonetheless, via the formation of a hydroxyapatite layer and the ability to control the pH increase, we speculate that implant integration in vivo and bone regeneration may benefit from this concept. Full article
(This article belongs to the Special Issue Implantable Materials for Drug Delivery in Tissue Regeneration)
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23 pages, 2492 KiB  
Article
A Versatile Macromer-Based Glycosaminoglycan (sHA3) Decorated Biomaterial for Pro-Osteogenic Scavenging of Wnt Antagonists
by Mathis Gronbach, Franziska Mitrach, Stephanie Möller, Sandra Rother, Sabrina Friebe, Stefan G. Mayr, Matthias Schnabelrauch, Vera Hintze, Michael C. Hacker and Michaela Schulz-Siegmund
Pharmaceutics 2020, 12(11), 1037; https://doi.org/10.3390/pharmaceutics12111037 - 29 Oct 2020
Cited by 4 | Viewed by 2705
Abstract
High serum levels of Wnt antagonists are known to be involved in delayed bone defect healing. Pharmaceutically active implant materials that can modulate the micromilieu of bone defects with regard to Wnt antagonists are therefore considered promising to support defect regeneration. In this [...] Read more.
High serum levels of Wnt antagonists are known to be involved in delayed bone defect healing. Pharmaceutically active implant materials that can modulate the micromilieu of bone defects with regard to Wnt antagonists are therefore considered promising to support defect regeneration. In this study, we show the versatility of a macromer based biomaterial platform to systematically optimize covalent surface decoration with high-sulfated glycosaminoglycans (sHA3) for efficient scavenging of Wnt antagonist sclerostin. Film surfaces representing scaffold implants were cross-copolymerized from three-armed biodegradable macromers and glycidylmethacrylate and covalently decorated with various polyetheramine linkers. The impact of linker properties (size, branching) and density on sHA3 functionalization efficiency and scavenging capacities for sclerostin was tested. The copolymerized 2D system allowed for finding an optimal, cytocompatible formulation for sHA3 functionalization. On these optimized sHA3 decorated films, we showed efficient scavenging of Wnt antagonists DKK1 and sclerostin, whereas Wnt agonist Wnt3a remained in the medium of differentiating SaOS-2 and hMSC. Consequently, qualitative and quantitative analysis of hydroxyapatite staining as a measure for osteogenic differentiation revealed superior mineralization on sHA3 materials. In conclusion, we showed how our versatile material platform enables us to efficiently scavenge and inactivate Wnt antagonists from the osteogenic micromilieu. We consider this a promising approach to reduce the negative effects of Wnt antagonists in regeneration of bone defects via sHA3 decorated macromer based macroporous implants. Full article
(This article belongs to the Special Issue Implantable Materials for Drug Delivery in Tissue Regeneration)
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25 pages, 6140 KiB  
Article
In Vivo Validation of Spray-Dried Mesoporous Bioactive Glass Microspheres Acting as Prolonged Local Release Systems for BMP-2 to Support Bone Regeneration
by Julia C. Berkmann, Aaron X. Herrera Martin, Carlotta Pontremoli, Kai Zheng, Christian H. Bucher, Agnes Ellinghaus, Aldo R. Boccaccini, Sonia Fiorilli, Chiara Vitale Brovarone, Georg N. Duda and Katharina Schmidt-Bleek
Pharmaceutics 2020, 12(9), 823; https://doi.org/10.3390/pharmaceutics12090823 - 28 Aug 2020
Cited by 18 | Viewed by 3386
Abstract
Bone morphogenetic protein-2 (BMP-2) is a known key mediator of physiological bone regeneration and is clinically approved for selected musculoskeletal interventions. Yet, broad usage of this growth factor is impeded due to side effects that are majorly evoked by high dosages and burst [...] Read more.
Bone morphogenetic protein-2 (BMP-2) is a known key mediator of physiological bone regeneration and is clinically approved for selected musculoskeletal interventions. Yet, broad usage of this growth factor is impeded due to side effects that are majorly evoked by high dosages and burst release kinetics. In this study, mesoporous bioactive glass microspheres (MBGs), produced by an aerosol-assisted spray-drying scalable process, were loaded with BMP-2 resulting in prolonged, low-dose BMP-2 release without affecting the material characteristics. In vitro, MBGs were found to be cytocompatible and to induce a pro-osteogenic response in primary human mesenchymal stromal cells (MSCs). In a pre-clinical rodent model, BMP-2 loaded MBGs significantly enhanced bone formation and influenced the microarchitecture of newly formed bone. The MBG carriers alone performed equal to the untreated (empty) control in most parameters tested, while additionally exerting mild pro-angiogenic effects. Using MBGs as a biocompatible, pro-regenerative carrier for local and sustained low dose BMP-2 release could limit side effects, thus enabling a safer usage of BMP-2 as a potent pro-osteogenic growth factor. Full article
(This article belongs to the Special Issue Implantable Materials for Drug Delivery in Tissue Regeneration)
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16 pages, 2251 KiB  
Article
Acemannan Used as an Implantable Biomaterial for Vital Pulp Therapy of Immature Permanent Teeth Induced Continued Root Formation
by Tien Thuy Vu, Minh Truong Nguyen, Polkit Sangvanich, Quang Ngoc Nguyen and Pasutha Thunyakitpisal
Pharmaceutics 2020, 12(7), 644; https://doi.org/10.3390/pharmaceutics12070644 - 8 Jul 2020
Cited by 27 | Viewed by 3880
Abstract
Direct pulp-capping, a vital pulp therapy, is used to protect and preserve pulp vitality by applying a biomaterial on the pulp exposure site. Acemannan, a polysaccharide extracted from Aloe vera, induces osteodentin-bridge formation to cover the exposure site in vivo. We evaluated [...] Read more.
Direct pulp-capping, a vital pulp therapy, is used to protect and preserve pulp vitality by applying a biomaterial on the pulp exposure site. Acemannan, a polysaccharide extracted from Aloe vera, induces osteodentin-bridge formation to cover the exposure site in vivo. We evaluated the effect of acemannan sponges on partial pulpotomized permanent teeth with caries or accident-induced pulp exposure (n = 50). After removing infected dentin and inflamed pulp tissue, the teeth were randomly divided into acemannan or control (mineral trioxide aggregate (MTA) groups (n = 25). The teeth were examined immediately after treatment (baseline) and at 6- and 12-month follow-ups for clinical and cone beam computed tomography (CBCT) examination. The three-dimensional tooth length and root apex area were simulated to determine treatment success. We found that the overall success rate in the acemannan and MTA groups from baseline to 12-month follow-up was 90.91% and 95.65%, respectively, with no significant difference between the two groups (p > 0.05). In the success teeth in both groups, the root length increased, and the apex area significantly decreased (p < 0.05), indicating continued root formation. Our results suggest that acemannan is a promising low-cost biomaterial for partial pulpotomy treatment for immature permanent teeth requiring vital pulp therapy. Full article
(This article belongs to the Special Issue Implantable Materials for Drug Delivery in Tissue Regeneration)
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