Classification of Biomaterials Used in Delivery Systems: Comparison
Please note this is a comparison between Version 2 by Conner Chen and Version 1 by lincui da.

A delivery system generally utilizes biomaterials as carriers to embed, deliver, and release bioactive substances at the desired site under controlled conditions. Among them, inorganic and organic biomaterials are popular in delivery system-based regenerative medicine.

  • controlled release
  • regeneration medicine
  • urinary system injury

1. Introduction

The lower genitourinary (GU) system refers to the urinary and reproductive organs apart from the kidney and ureter, such as the urethra, bladder, ovaries, uterus, vagina, scrotum, penis, and testes [1]. Lower GU trauma, usually caused by disease, accident, or iatrogenesis, has long been an important medical problem because the affected tissues generally fail to regenerate after injury, resulting in serious urinary, sexual, reproductive, and psychological consequences [2,3,4][2][3][4]. Therefore, improved strategies are urgently needed for the structural and functional reconstruction of damaged lower GU tissues.
Regenerative medicine, a multidisciplinary field that seeks to efficiently repair and regenerate injured tissues after trauma, has emerged as an attractive option for the treatment of lower GU damage [5,6,7][5][6][7]. Further, the use of bioactive agents (e.g., drugs, growth factors, cytokines, hormones, inhibitors, genes, and even living cells) to modulate cellular behavior and treat tissues may help improve current regenerative medicine approaches [8,9,10][8][9][10]. However, the direct application of bioactive agents in regenerative medicine is limited by their lack of stability, solubility, and ease of migration from the application site, making them ineffective for sustained treatment [5,11][5][11]. A delivery system refers to a device or formulation that enables spatiotemporal controlled release of active substances with adequate dosage and correct form at the target site [12,13,14][12][13][14]. Delivery systems aim to enhance the bioavailability of active substances, extend the duration of pharmacological action, increase treatment efficacy, and reduce adverse effects, thereby, acting as an important driving force for regenerative therapy [13].
However, regarding the delivery of active compounds, there is still a significant gap for improvement in loading efficiency, stability, therapeutic activity, and their spatiotemporal controlled release profile. Therefore, various exploration steps have been taken to develop sophisticated bioactive agent delivery systems focused on the types of biomaterials, delivery systems, and loading strategies. For instance, to endow biomaterials with additional characteristics that are beneficial to regenerative therapies, different composite materials, crosslinking methods, and chemical modifications have been developed [15,16,17,18][15][16][17][18]. Furthermore, fabrication methods which may affect drug encapsulation, release, and biological efficacy, such as cell exosome production, three-dimensional (3D) printing, electrospinning, and microfluidics, have been used to produce diverse forms of delivery systems for the sequential delivery of therapeutic substances [19,20,21,22,23][19][20][21][22][23]. In addition, many types of loading strategies, such as adding stabilizing excipients, covalent immobilization, in vitro loading, and structure optimization have been utilized to enhance bioavailability and prevent burst release [24,25,26,27][24][25][26][27].

2. Classification of Biomaterials Used in Delivery Systems

A delivery system generally utilizes biomaterials as carriers to embed, deliver, and release bioactive substances at the desired site under controlled conditions [28,29][28][29]. Among them, inorganic and organic biomaterials are popular in delivery system-based regenerative medicine.

2.1. Inorganic Biomaterials

Inorganic biomaterials, including but not limited to metals, metallic oxides, and glasses, have been explored to fabricate delivery systems for soft tissue therapeutic applications. Metals and metallic oxides are considered to be potential carriers because of their well-defined structures and ease of chemical functionalization [30]. In addition to their carrier function, some metals or metallic oxides, such as gold, silver, iron oxide, zinc oxide, and cerium oxide, possess interesting features such as antibacterial activity, antioxidant properties, and the capacity to magnetically drive macrophage polarization [31,32][31][32]. Iron oxide nanoparticles are an excellent example of an inorganic biomaterial that has been intensively studied for use in regenerative therapy. Wu et al. fabricated basic fibroblast growth factor (bFGF)-loaded heparin dopamine conjugate-coated Fe3O4 nanoparticles (bFGF-HDC@Fe3O4) through surface immobilization [25]. The stability and bioactivity of bFGF was tested by evaluating the effect on NIH 3T3 cell viability after being reacted with bFGF-HDC@Fe3O4 nanoparticles at various conditions that may be encountered during preparation, storage, or application (e.g., 4 °C, 55 °C, pH 5.0, 1% trypsin, and 1% trifluoroacetic acid) [25]. The cell growth rate was much higher in the bFGF-HDC@Fe3O4 group than in the free bFGF group, particularly under harsh conditions, demonstrating that HDC@Fe3O4 was capable of effectively maintaining the stability of bFGF [25]. These nanoparticles also demonstrated good stability and controlled release, gradually releasing 40% of the bFGF and retaining 70% protein activity over 12 days [25]. Moreover, with the help of an external magnetic field, bFGF-HDC@Fe3O4 nanoparticles were efficiently distributed to the mitochondria of macrophages, thus, promoting anti-inflammatory phenotype macrophage polarization to accelerate tissue regeneration [25]. In 2020, Khosravi et al. developed curcumin-loaded superparamagnetic iron oxide nanoparticles (SPIONs) to treat testes damage caused by heat stress [33]. In another study, ferucarbotran, a commercial agent composed of SPIONs, was used to deliver bone marrow mesenchymal stem cells (MSCs) for the repairment of resected bladder tissue [34]. Using this method, the MSCs acquired magnetic characteristics allowing their accumulation in damaged areas under the direction of an external magnetic field, effectively enhancing tissue regeneration in a minimally invasive approach [34].
Mesoporous glass (e.g., borates, silicates, and phosphates) nanoparticles have been studied as carriers for regenerative medicine owing to their remarkable physicochemical properties, including ease of synthesis and functionalization, low mass density, controllable nanoparticle size, tunable microstructure, high specific surface area, and cytocompatibility [35]. In 2020, Hamam et al. developed curcumin-loaded mesoporous silica particles for tissue regeneration [36]. In another example, ultrasmall ceria nanocrystals with controlled reactive oxygen species (ROS) scavenging capability were loaded on uniform mesoporous silica nanoparticles to alleviate oxidative damage at the injury site [37]. These ceria-loaded nanoparticles induced regenerative healing effects, indicating their great potential for wound repair applications in which ROS-scavenging activity is beneficial [37]. In addition, Wang et al. developed poly(amidoamine) dendrimers modified mesoporous silica nanoparticles with controlled drug release properties for bladder cancer therapy [38]. This delivery system showed excellent mucoadhesive capabilities on bladder wall, which could provide enlightenment for the development of bioactive agent-based delivery systems for bladder regenerative treatment.

2.2. Organic Biomaterials

Organic biomaterials can be divided into synthetic polymeric and bioderived materials, depending on their source. Polymeric materials that are accurately synthesized through reproducible industrial processes have been widely utilized in regenerative medicine applications because of their tunable physicochemical properties [39,40][39][40]. In addition, these materials are popular for the sustained or controlled release of encapsulated active substances. Thus, polymeric materials, such as polylactide-co-glycolide (PLGA), polyethylene glycol (PEG), polyvinyl alcohol (PVA), and poly (ester amide) (PEA) are suitable candidates for carriers of bioactive agents in tissue regeneration. The possible release mechanisms of bioactive agents from synthetic polymers include time and condition-dependent surface erosion, desorption, and swelling and diffusion [14]. PLGA, which possesses a tunable degradation rate and induces minimal systemic cytotoxicity, is an attractive FDA-approved polyester in applications that require long-term delivery of therapeutic substances. Ciardulli et al. encapsulated human growth differentiation factor 5 in a PLGA nanocarrier for controlled delivery, thus, promoting tissue regeneration events [41]. PEG is another polyester that has received significant attention for its tunable geometry and hydrophilicity. Recently, Sok et al. developed a PEG-based hydrogel that showed promising results for delivery of aspirin-triggered resolvin D1 and recombinant human interleukin 10, resulting in recruitment of immune cells, their polarization towards pro-regenerative phenotypes, and subsequent healing of trauma wounds [42]. Liang et al. fabricated PEG—poly (ε-caprolactone-co-lactide)-based thermosensitive delivery system to deliver adipose stem cell-derived exosomes under sustained manner in corpus cavernous, and finally ended with erectile function restored [22]. PVA is a food and drug administration (FDA) approved polyol that can acquire ROS-responsive capacity after reacting with benzoboric acid [43]. Li et al. developed a hydrogel composed of PVA and benzoboric acid to deliver bFGF, demonstrating promising results for the repair of tissues with high ROS microenvironments [43]. PEA, a cationic polymer consisting of ester and amino groups synthesized from natural active biomolecules, is nontoxic and possesses excellent biodegradability, biocompatibility, and mechanical properties [44]. Yuan et al. recently synthesized PEA using L-arginine, L-phenylalanine, and inositol as raw materials [44]. Vitamin E encapsulated in PEA showed excellent antioxidative and anti-inflammatory properties in tissue engineering applications [44]. In 2020, PEA-plasmid polyplex-based delivery systems were used successfully to deliver exogenous deoxyribonucleic acid to the vagina/cervix without diffusing to nearby organs, which showed it immense application potential in vagina/cervix regenerative therapies [45]. Bioderived materials are defined as macromolecules extracted from microorganisms, animals, or plants [46,47,48][46][47][48]. Advantages such as high availability, biocompatibility, and bioactivity have facilitated the use of bioderived materials as delivery systems for therapeutic substance release and tissue repair [49,50][49][50]. Among them, proteins (including, fibroin, collagen, and keratin), polysaccharides (such as, glycosaminoglycans, alginate, chitosan, plant origin natural gum, cellulose, and gellan gum), lipids (such as liposomes and saturated fatty acids), extracellular vesicles (EVs), and extracellular matrix (ECM) have been extensively investigated and are reviewed in detail elsewhere [51,52,53,54,55,56,57,58,59][51][52][53][54][55][56][57][58][59].

References

  1. Tullington, J.E.; Blecker, N. Lower Genitourinary Trauma; StatPearls Publishing: Treasure Island, FL, USA, 2022.
  2. Balzano, F.L.; Hudak, S.J. Military genitourinary injuries: Past, present, and future. Transl. Androl. Urol. 2018, 7, 646–652.
  3. Bayne, D.; Zaid, U.; Alwaal, A.; Harris, C.; McAninch, J.; Breyer, B. Lower genitourinary tract trauma. Trauma 2015, 18, 12–20.
  4. Caneparo, C.; Sorroza-Martinez, L.; Chabaud, S.; Fradette, J.; Bolduc, S. Considerations for the clinical use of stem cells in genitourinary regenerative medicine. World J. Stem Cells 2021, 13, 1480–1512.
  5. Atienza-Roca, P.; Cui, X.; Hooper, G.J.; Woodfield, T.B.F.; Lim, K.S. Growth factor delivery systems for tissue engineering and regenerative medicine. Adv. Exp. Med. Biol. 2018, 1078, 245–269.
  6. Doostmohammadi, M.; Forootanfar, H.; Ramakrishna, S. Regenerative medicine and drug delivery: Progress via electrospun biomaterials. Mater. Sci. Eng. C Mater. Biol. Appl. 2020, 109, 110521.
  7. Tang, X.; Sun, C. The roles of MicroRNAs in neural regenerative medicine. Exp. Neurol. 2020, 332, 113394.
  8. Caballero Aguilar, L.M.; Silva, S.M.; Moulton, S.E. Growth factor delivery: Defining the next generation platforms for tissue engineering. J. Control. Release 2019, 306, 40–58.
  9. Wang, X.; Liu, Z.; Sandoval-Salaiza, D.A.; Afewerki, S.; Jimenez-Rodriguez, M.G.; Sanchez-Melgar, L.; Güemes-Aguilar, G.; Gonzalez-Sanchez, D.G.; Noble, O.; Lerma, C.; et al. Nanostructured non-newtonian drug delivery barrier prevents postoperative intrapericardial adhesions. ACS Appl. Mater. Interfaces 2021, 13, 29231–29246.
  10. Zhang, Z.; Zhang, X. Curcumin loading on alginate nano-micelle for anti-infection and colonic wound healing. J. Biomed. Nanotechnol. 2021, 17, 1160–1169.
  11. Subbiah, R.; Guldberg, R.E. Materials science and design principles of growth factor delivery systems in tissue engineering and regenerative medicine. Adv. Healthc. Mater. 2019, 8, e1801000.
  12. Hafeez, M.N.; d’Avanzo, N.; Russo, V.; Di Marzio, L.; Cilurzo, F.; Paolino, D.; Fresta, M.; Barboni, B.; Santos, H.A.; Celia, C. Tendon tissue repair in prospective of drug delivery, regenerative medicines, and innovative bioscaffolds. Stem Cells Int. 2021, 2021, 1488829.
  13. Liu, R.; Poma, A. Advances in molecularly imprinted polymers as drug delivery systems. Molecules 2021, 26, 3589.
  14. Harish, V.; Tewari, D.; Gaur, M.; Yadav, A.B.; Swaroop, S.; Bechelany, M.; Barhoum, A. Review on nanoparticles and nanostructured materials: Bioimaging, biosensing, drug delivery, tissue engineering, antimicrobial, and agro-food applications. Nanomaterials 2022, 12, 457.
  15. Colucci, F.; Mancini, V.; Mattu, C.; Boffito, M. Designing multifunctional devices for regenerative pharmacology based on 3D scaffolds, drug-loaded nanoparticles, and thermosensitive hydrogels: A proof-of-concept study. Pharmaceutics 2021, 13, 464.
  16. Mohseni, M.; Shokrollahi, P.; Barzin, J. Impact of supramolecular interactions on delivery of dexamethasone from a physical network of gelatin/ZnHAp composite scaffold. Int. J. Pharm. 2022, 615, 121520.
  17. Li, X.; Wang, C.; Wang, L.; Huang, R.; Li, W.C.; Wang, X.; Wong, S.S.W.; Cai, Z.; Leung, K.C.; Jin, L. A glutathione-responsive silica-based nanosystem capped with in-situ polymerized cell-penetrating poly(disulfide)s for precisely modulating immuno-inflammatory responses. J. Colloid Interface Sci. 2022, 614, 322–336.
  18. Wnorowska, U.; Fiedoruk, K.; Piktel, E.; Prasad, S.V.; Sulik, M.; Janion, M.; Daniluk, T.; Savage, P.B.; Bucki, R. Nanoantibiotics containing membrane-active human cathelicidin LL-37 or synthetic ceragenins attached to the surface of magnetic nanoparticles as novel and innovative therapeutic tools: Current status and potential future applications. J. Nanobiotechnol. 2020, 18, 3.
  19. Kimicata, M.; Mahadik, B.; Fisher, J.P. Long-term sustained drug delivery via 3D printed masks for the development of a heparin-loaded interlayer in vascular tissue engineering applications. ACS Appl. Mater. Interfaces 2021, 13, 50812–50822.
  20. Lin, J.; Wang, Z.; Huang, J.; Tang, S.; Saiding, Q.; Zhu, Q.; Cui, W. Microenvironment-protected exosome-hydrogel for facilitating endometrial regeneration, fertility restoration, and live birth of offspring. Small 2021, 17, e2007235.
  21. Wang, L.; Cheng, W.; Zhu, J.; Li, W.; Li, D.; Yang, X.; Zhao, W.; Ren, M.; Ren, J.; Mo, X.; et al. Electrospun nanoyarn and exosomes of adipose-derived stem cells for urethral regeneration: Evaluations in vitro and in vivo. Colloids Surf. B Biointerfaces 2022, 209, 112218.
  22. Liang, L.; Shen, Y.; Dong, Z.; Gu, X. Photoacoustic image-guided corpus cavernosum intratunical injection of adipose stem cell-derived exosomes loaded polydopamine thermosensitive hydrogel for erectile dysfunction treatment. Bioact. Mater. 2022, 9, 147–156.
  23. Gimondi, S.; Guimarães, C.F.; Vieira, S.F.; Gonçalves, V.M.F.; Tiritan, M.E.; Reis, R.L.; Ferreira, H.; Neves, N.M. Microfluidic mixing system for precise PLGA-PEG nanoparticles size control. Nanomedicine 2022, 40, 102482.
  24. Guo, G.; Gong, T.; Shen, H.; Wang, Q.; Jiang, F.; Tang, J.; Jiang, X.; Wang, J.; Zhang, X.; Bu, W. Self-amplification immunomodulatory strategy for tissue regeneration in diabetes based on cytokine-zifs system. Adv. Funct. Meter. 2021, 31, 2100795.
  25. Wu, J.; Zhu, J.; Wu, Q.; An, Y.; Wang, K.; Xuan, T.; Zhang, J.; Song, W.; He, H.; Song, L.; et al. Mussel-inspired surface immobilization of heparin on magnetic nanoparticles for enhanced wound repair via sustained release of a growth factor and M2 macrophage polarization. ACS Appl. Mater. Interfaces 2021, 13, 2230–2244.
  26. Babić Radić, M.M.; Filipović, V.V.; Vukomanović, M.; Nikodinović, R.J.; Tomić, S.L. Degradable 2-hydroxyethyl methacrylate/gelatin/alginate hydrogels infused by nanocolloidal graphene oxide as promising drug delivery and scaffolding biomaterials. Gels 2022, 8, 22.
  27. Perteghella, S.; Crivelli, B.; Catenacci, L.; Sorrenti, M.; Bruni, G.; Necchi, V.; Vigani, B.; Sorlini, M.; Torre, M.L.; Chlapanidas, T. Stem cell-extracellular vesicles as drug delivery systems: New frontiers for silk/curcumin nanoparticles. Int. J. Pharm. 2017, 520, 86–97.
  28. Gaurav, I.; Thakur, A.; Iyaswamy, A.; Wang, X.; Chen, X.; Yang, Z. Factors affecting extracellular vesicles based drug delivery systems. Molecules 2021, 26, 1544.
  29. Skopinska-Wisniewska, J.; Flor, S.; Kozlowska, J. From supramolecular hydrogels to multifunctional carriers for biologically active substances. Int. J. Mol. Sci. 2021, 22, 7402.
  30. Sun, Y.; Zheng, L.; Yang, Y.; Qian, X.; Fu, T.; Li, X.; Yang, Z.; Yan, H.; Cui, C.; Tan, W. Metal-organic framework nanocarriers for drug delivery in biomedical applications. Nanomicro. Lett. 2020, 12, 103.
  31. Filippi, M.; Garello, F.; Yasa, O.; Kasamkattil, J.; Scherberich, A.; Katzschmann, R.K. Engineered magnetic nanocomposites to modulate cellular function. Small 2022, 18, e2104079.
  32. Da, L.C.; Huang, Y.Z.; Xie, H.Q.; Zheng, B.H.; Huang, Y.C.; Du, S.R. Membranous extracellular matrix-based scaffolds for skin wound healing. Pharmaceutics 2021, 13, 1796.
  33. Khosravi, A.; Hasani, A.; Rahimi, K.; Aliaghaei, A.; Pirani, M.; Azad, N.; Ramezani, F.; Tamimi, A.; Behnam, P.; Raoofi, A.; et al. Ameliorating effects of curcumin-loaded superparamagnetic iron oxide nanoparticles (SPIONs) on the mouse testis exposed to the transient hyperthermia: A molecular and stereological study. Acta Histochem. 2020, 122, 151632.
  34. Sadahide, K.; Teishima, J.; Inoue, S.; Tamura, T.; Kamei, N.; Adachi, N.; Matsubara, A. Endoscopic repair of the urinary bladder with magnetically labeled mesenchymal stem cells: Preliminary report. Regen. Ther. 2019, 10, 46–53.
  35. Rastegari, E.; Hsiao, Y.J.; Lai, W.Y.; Lai, Y.H.; Yang, T.C.; Chen, S.J.; Huang, P.I.; Chiou, S.H.; Mou, C.Y.; Yueh, C. An update on mesoporous silica nanoparticle applications in nanomedicine. Pharmaceutics 2021, 13, 1067.
  36. Hamam, F.; Nasr, A. Curcumin-loaded mesoporous silica particles as wound-healing agent: An in vivo study. Saudi J. Med. Med. Sci. 2020, 8, 17–24.
  37. Wu, H.; Li, F.; Wang, S.; Lu, J.; Li, J.; Du, Y.; Sun, X.; Chen, X.; Gao, J.; Ling, D. Ceria nanocrystals decorated mesoporous silica nanoparticle based ROS-scavenging tissue adhesive for highly efficient regenerative wound healing. Biomaterials 2018, 151, 66–77.
  38. Wang, B.; Zhang, K.; Wang, J.; Zhao, R.; Zhang, Q.; Kong, X. Poly(amidoamine)-modified mesoporous silica nanoparticles as a mucoadhesive drug delivery system for potential bladder cancer therapy. Colloids Surf. B Biointerfaces 2020, 189, 110832.
  39. Henry, N.; Clouet, J.; Le Bideau, J.; Le Visage, C.; Guicheux, J. Innovative strategies for intervertebral disc regenerative medicine: From cell therapies to multiscale delivery systems. Biotechnol. Adv. 2018, 36, 281–294.
  40. Abbas, A.; Zhang, C.; Asad, M.; Waqas, A.; Khatoon, A.; Hussain, S.; Mir, S.H. Recent developments in artificial super-wettable surfaces based on bioinspired polymeric materials for biomedical applications. Polymers 2022, 14, 238.
  41. Ciardulli, M.C.; Lovecchio, J.; Scala, P.; Lamparelli, E.P.; Dale, T.P.; Giudice, V.; Giordano, E.; Selleri, C.; Forsyth, N.R.; Maffulli, N.; et al. 3D biomimetic scaffold for growth factor controlled delivery: An in-vitro study of tenogenic events on wharton’s jelly mesenchymal stem cells. Pharmaceutics 2021, 13, 1448.
  42. Sok, M.C.P.; Baker, N.; McClain, C.; Lim, H.S.; Turner, T.; Hymel, L.; Ogle, M.; Olingy, C.; Palacios, J.I.; Garcia, J.R.; et al. Dual delivery of IL-10 and AT-RvD1 from PEG hydrogels polarize immune cells towards pro-regenerative phenotypes. Biomaterials 2021, 268, 120475.
  43. Li, Z.; Zhu, D.; Hui, Q.; Bi, J.; Yu, B.; Huang, Z.; Hu, S.; Wang, Z.; Caranasos, T.; Rossi, J.; et al. Injection of ROS-responsive hydrogel loaded with basic fibroblast growth factor into the pericardial cavity for heart repair. Adv. Funct. Mater. 2021, 31, 2004377.
  44. Yuan, Q.; Huang, J.; Xian, C.; Wu, J. Amino acid- and growth factor-based multifunctional nanocapsules for the modulation of the local microenvironment in tissue engineering. ACS Appl. Mater. Interfaces 2021, 13, 2165–2178.
  45. Niu, G.; Jin, Z.; Zhang, C.; He, D.; Gao, X.; Zou, C.; Zhang, W.; Ding, J.; Das, B.C.; Severinov, K.; et al. An effective vaginal gel to deliver CRISPR/Cas9 system encapsulated in poly (beta-amino ester) nanoparticles for vaginal gene therapy. EBioMedicine 2020, 58, 102897.
  46. Kandhasamy, S.; Liang, B.; Yang, D.P.; Zeng, Y. Antibacterial vitamin K3 carnosine peptide-laden silk fibroin electrospun fibers for improvement of skin wound healing in diabetic rats. ACS Appl. Bio. Mater. 2021, 4, 4769–4788.
  47. Verma, A.; Tiwari, A.; Panda, P.K.; Saraf, S.; Jain, A.; Jain, S.K. Locust bean gum in drug delivery application. In Natural Polysaccharides in Drug Delivery and Biomedical Applications; Academic Press: Cambridge, MA, USA, 2019; pp. 203–222.
  48. Fey, C.; Betz, J.; Rosenbaum, C.; Kralisch, D.; Vielreicher, M.; Friedrich, O.; Metzger, M.; Zdzieblo, D. Bacterial nanocellulose as novel carrier for intestinal epithelial cells in drug delivery studies. Mater. Sci. Eng. C Mater. Biol. Appl. 2020, 109, 110613.
  49. Troy, E.; Tilbury, M.A.; Power, A.M.; Wall, J.G. Nature-based biomaterials and their application in biomedicine. Polymers 2021, 13, 3321.
  50. Liu, H.; Wang, C.; Li, C.; Qin, Y.; Wang, Z.; Yang, F.; Li, Z.; Wang, J. A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. RSC Adv. 2018, 8, 7533–7549.
  51. Dubnika, A.; Egle, K.; Skrinda-Melne, M.; Skadins, I.; Rajadas, J.; Salma, I. Development of vancomycin delivery systems based on autologous 3D platelet-rich fibrin matrices for bone tissue engineering. Biomedicines 2021, 9, 814.
  52. Koyyada, A.; Orsu, P. Natural gum polysaccharides as efficient tissue engineering and drug delivery biopolymers. J. Drug Deliv. Sci. Technol. 2021, 63, 102431.
  53. Carvalho, T.; Guedes, G.; Sousa, F.L.; Freire, C.S.R.; Santos, H.A. Latest advances on bacterial cellulose-based materials for wound healing, delivery systems, and tissue engineering. Biotechnol. J. 2019, 14, e1900059.
  54. Miao, T.; Wang, J.; Zeng, Y.; Liu, G.; Chen, X. Polysaccharide-based controlled release systems for therapeutics delivery and tissue engineering: From bench to bedside. Adv. Sci. 2018, 5, 1700513.
  55. Palumbo, F.S.; Federico, S.; Pitarresi, G.; Fiorica, C.; Giammona, G. Gellan gum-based delivery systems of therapeutic agents and cells. Carbohydr. Polym. 2020, 229, 115430.
  56. Xue, K.; Lv, S.; Zhu, C. Bringing naturally-occurring saturated fatty acids into biomedical research. J. Mater. Chem. B 2021, 9, 6973–6987.
  57. Filipczak, N.; Yalamarty, S.S.K.; Li, X.; Khan, M.M.; Parveen, F.; Torchilin, V. Lipid-based drug delivery systems in regenerative medicine. Materials 2021, 14, 5371.
  58. Johnson, J.; Wu, Y.W.; Blyth, C.; Lichtfuss, G.; Goubran, H.; Burnouf, T. Prospective therapeutic applications of platelet extracellular vesicles. Trends Biotechnol. 2021, 39, 598–612.
  59. Serna, J.A.; Rueda-Gensini, L.; Céspedes-Valenzuela, D.N.; Cifuentes, J.; Cruz, J.C.; Muñoz-Camargo, C. Recent advances on stimuli-responsive hydrogels based on tissue-derived ecms and their components: Towards improving functionality for tissue engineering and controlled drug delivery. Polymers 2021, 13, 3263.
More