Biodegradable Scaffolds in Tissue Engineering

Öz

Biodegradable scaffolds are critical components in tissue engineering, designed to support regenerative processes by providing a biomimetic microenvironment that facilitates cellular adhesion, proliferation, and differentiation. This review comprehensively discusses the material properties, fabrication techniques, and tissue-specific applications of biodegradable scaffolds. Both natural (e.g., collagen, gelatin, alginate) and synthetic (e.g., PLA, PLGA, PCL) polymers are employed either individually or in composite forms to balance biological compatibility with mechanical integrity, allowing for scaffold designs tailored to the distinct needs of various tissues such as bone, cartilage, skin, and gingiva. The article highlights that scaffolds are not merely passive structural supports but also active regenerative platforms through the controlled delivery of biological agents such as growth factors, antibiotics, and chemotherapeutic drugs. Advanced fabrication techniques, including electrospinning and 3D bioprinting, enable precise control over drug release kinetics and scaffold architecture, thus enhancing therapeutic outcomes while minimizing systemic toxicity. Scaffold-based delivery systems have demonstrated significant promise in critical clinical contexts, including cancer therapy, wound healing, and infection control. In conclusion, biodegradable scaffolds represent multifunctional biomaterials capable of guiding cellular and molecular events during tissue regeneration. Future developments are expected to focus on smart, stimuli-responsive polymers, spatiotemporal growth factor release, and personalized scaffold fabrication to further enhance their translational potential in clinical regenerative medicine.

Anahtar Kelimeler

• Biodegradable scaffolds
• Tissue engineering
• Biomaterial design
• Controlled drug release

Doku Mühendisliğinde Biyobozunur İskeleler

Öz

Biyobozunur doku iskeleleri (scaffoldlar), doku mühendisliğinde rejeneratif süreçleri desteklemek amacıyla geliştirilmiş kritik biyomalzemelerdir. Bu derleme, hücresel tutunma, proliferasyon ve farklılaşmayı destekleyen biyomimetik mikroçevreler oluşturan biyobozunur iskelelerin malzeme özellikleri, üretim yöntemleri ve dokuya özgü uygulamalarını kapsamlı şekilde ele almaktadır. Doğal (kolajen, jelatin, alginat) ve sentetik (PLA, PLGA, PCL) polimerlerin tekil veya kompozit formlarda kullanımı, biyolojik uyum ile mekanik dayanım arasında denge kurmayı mümkün kılmakta ve farklı doku türlerine özel scaffold tasarımlarına olanak tanımaktadır. Kemik, kıkırdak, deri ve gingival dokular gibi hedef dokuların kendine özgü biyomekanik ve hücresel gereksinimleri doğrultusunda, iskelelerin porozitesi, bozunma profili, elastikiyeti ve yük taşıma kapasitesi optimize edilmektedir. Makale, scaffoldların yalnızca geçici yapısal destek sunan pasif platformlar değil, aynı zamanda büyüme faktörleri, antibiyotikler ve kemoterapötik ajanlar gibi biyolojik yüklerin kontrollü salımı yoluyla aktif rejeneratif modüller olduğunu vurgulamaktadır. Özellikle elektrospinning ve 3D biyobasım gibi ileri üretim teknikleri, hedefe yönelik ilaç iletimini ve biyolojik mikroçevreyi hassas şekilde düzenleme potansiyeli sunmaktadır. Scaffold tabanlı ilaç salım sistemleri, kanser tedavisi, yara iyileşmesi ve enfeksiyon kontrolü gibi kritik klinik alanlarda terapötik etkinliği artırmakta ve sistemik toksisiteyi azaltmaktadır. Sonuç olarak, biyobozunur doku iskeleleri, hücresel ve moleküler düzeyde yenilenme süreçlerini yönlendiren akıllı biyomalzeme sistemleri olarak öne çıkmaktadır. Gelecekte uyaran-duyarlı polimerler, çoklu büyüme faktörü salımı ve kişiselleştirilmiş scaffold üretimi gibi yaklaşımlarla, bu yapıların klinik translasyon potansiyelinin daha da artması beklenmektedir.

Anahtar Kelimeler

• Biyobozunur doku iskeleleri
• Doku mühendisliği
• Biyomalzeme tasarımı
• Kontrollü ilaç salımı

Kaynakça

1. 1. Lauritano, D., et al., Nanomaterials for Periodontal Tissue Engineering: Chitosan-Based Scaffolds. A Systematic Review. Nanomaterials, 2020. 10(4): p. 605.
2. 2. Modrák, M., et al., Biodegradable Materials for Tissue Engineering: Development, Classification and Current Applications. Journal of Functional Biomaterials, 2023. 14(3): p. 159.
3. 3. Echeverria Molina, M.I., K.G. Malollari, and K. Komvopoulos, Design Challenges in Polymeric Scaffolds for Tissue Engineering. Front Bioeng Biotechnol, 2021. 9: p. 617141.
4. 4. Krishani, M., et al., Development of Scaffolds from Bio-Based Natural Materials for Tissue Regeneration Applications: A Review. Gels, 2023. 9(2).
5. 5. Karageorgiou, V. and D. Kaplan, Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials, 2005. 26(27): p. 5474-91.
6. 6. Sheikh, Z., et al., Macrophages, Foreign Body Giant Cells and Their Response to Implantable Biomaterials. Materials (Basel), 2015. 8(9): p. 5671-5701.
7. 7. Zhao, X., et al., Applications of Biocompatible Scaffold Materials in Stem Cell-Based Cartilage Tissue Engineering. Front Bioeng Biotechnol, 2021. 9: p. 603444.
8. 8. Kelleci, K., et al., Particulate and non-particle adjuvants in Leishmaniasis vaccine designs: A review. Journal of Vector Borne Diseases, 2023. 60(2): p. 125-141.

9. 9. Kelleci, K., et al., Immunomodulatory activity of polycaprolactone nanoparticles with calcium phosphate salts against Leishmania infantum infection. Asian Pacific Journal of Tropical Biomedicine, 2024. 14(8): p. 359-368.
10. 10. Findrik Balogová, A., et al., In Vitro Degradation of Specimens Produced from PLA/PHB by Additive Manufacturing in Simulated Conditions. Polymers, 2021. 13(10): p. 1542.
11. 11. dehghan, M., M. khajeh mehrizi, and H. Nikukar, Modeling and optimizing a polycaprolactone/gelatin/polydimethylsiloxane nanofiber scaffold for tissue engineering: using response surface methodology. Journal of the Textile Institute, 2021. 112: p. 482-493.
12. 12. Koons, G.L., M. Diba, and A.G. Mikos, Materials design for bone-tissue engineering. Nature Reviews Materials, 2020. 5(8): p. 584-603.
13. 13. Biswal, T., Biopolymers for tissue engineering applications: A review. Materials Today: Proceedings, 2020. 41.
14. 14. Mohseni, M., et al., Assessment of tricalcium phosphate/collagen (TCP/collagene)nanocomposite scaffold compared with hydroxyapatite (HA) on healing of segmental femur bone defect in rabbits. Artif Cells Nanomed Biotechnol, 2018. 46(2): p. 242-249.
15. 15. Flores-Rojas, G.G., et al., Electrospun Scaffolds for Tissue Engineering: A Review. Macromol, 2023. 3: p. 524-553.
16. 16. Rezvani Ghomi, E., et al., Wound dressings: Current advances and future directions. Journal of Applied Polymer Science, 2019. 136.
17. 17. Ambekar, R. and B. Kandasubramanian, Progress in the Advancement of Porous Biopolymer Scaffold: Tissue Engineering Application. Industrial & Engineering Chemistry Research, 2019. 58: p. 6163-6194.
18. 18. Chaudhari, A.A., et al., Future Prospects for Scaffolding Methods and Biomaterials in Skin Tissue Engineering: A Review. Int J Mol Sci, 2016. 17(12).
19. 19. Cao, J., et al., Double crosslinked HLC-CCS hydrogel tissue engineering scaffold for skin wound healing. Int J Biol Macromol, 2020. 155: p. 625-635.
20. 20. Rahmani Del Bakhshayesh, A., et al., Recent advances on biomedical applications of scaffolds in wound healing and dermal tissue engineering. Artif Cells Nanomed Biotechnol, 2018. 46(4): p. 691-705.
21. 21. Yang, L., et al., Biomass Microcapsules with Stem Cell Encapsulation for Bone Repair. Nanomicro Lett, 2021. 14(1): p. 4.
22. 22. Alavi, S.E., et al., Resorbable GBR Scaffolds in Oral and Maxillofacial Tissue Engineering: Design, Fabrication, and Applications. J Clin Med, 2023. 12(22).
23. 23. Aoki, K., et al., Bone-Regeneration Therapy Using Biodegradable Scaffolds: Calcium Phosphate Bioceramics and Biodegradable Polymers. Bioengineering (Basel), 2024. 11(2).
24. 24. Chocholata, P., V. Kulda, and V. Babuska, Fabrication of Scaffolds for Bone-Tissue Regeneration. Materials (Basel), 2019. 12(4).
25. 25. Aoki, K. and N. Saito, Biodegradable Polymers as Drug Delivery Systems for Bone Regeneration. Pharmaceutics, 2020. 12(2).
26. 26. Mauck, R.L., et al., Functional tissue engineering of articular cartilage through dynamic loading of chondrocyte-seeded agarose gels. J Biomech Eng, 2000. 122(3): p. 252-60.
27. 27. Toh, Y.C., et al., A microfluidic 3D hepatocyte chip for drug toxicity testing. Lab Chip, 2009. 9(14): p. 2026-35.
28. 28. Kuo, Y.C., H.F. Ku, and R. Rajesh, Chitosan/γ-poly(glutamic acid) scaffolds with surface-modified albumin, elastin and poly-l-lysine for cartilage tissue engineering. Mater Sci Eng C Mater Biol Appl, 2017. 78: p. 265-277.
29. 29. Bistolfi, A., et al., Regeneration of articular cartilage: Scaffold used in orthopedic surgery. A short handbook of available products for regenerative joints surgery. 2017. 1.
30. 30. Şeker, Ş., A.E. Elçin, and Y.M. Elçin, Macroporous elastic cryogels based on platelet lysate and oxidized dextran as tissue engineering scaffold: In vitro and in vivo evaluations. Mater Sci Eng C Mater Biol Appl, 2020. 110: p. 110703.
31. 31. Alkhursani, S.A., et al., Application of Nano-Inspired Scaffolds-Based Biopolymer Hydrogel for Bone and Periodontal Tissue Regeneration. Polymers (Basel), 2022. 14(18).
32. 32. Bhardwaj, N., D. Chouhan, and B.B. Mandal, 14 - 3D functional scaffolds for skin tissue engineering, in Functional 3D Tissue Engineering Scaffolds, Y. Deng and J. Kuiper, Editors. 2018, Woodhead Publishing. p. 345-365.
33. 33. Mallick, K.K. and S.C. Cox, Biomaterial scaffolds for tissue engineering. Front Biosci (Elite Ed), 2013. 5(1): p. 341-60.
34. 34. Place, E., et al., Synthetic Polymer Scaffolds for Tissue Engineering. Chemical Society reviews, 2009. 38: p. 1139-51.
35. 35. Ihlamur, M., et al., DOKU MÜHENDİSLİĞİ İÇİN İNSAN PLASENTAL KORYONUNDAN GELİŞTİRİLEN PLURİPOTENT HÜCRELERİN UYGULAMALARI. Uluslararası Batı Karadeniz Mühendislik ve Fen Bilimleri Dergisi, 2024. 6(2): p. 93-104.
36. 36. Zhang, Y.S. and A. Khademhosseini, Advances in engineering hydrogels. Science, 2017. 356(6337).
37. 37. Ma, P.X., Biomimetic materials for tissue engineering. Adv Drug Deliv Rev, 2008. 60(2): p. 184-98.
38. 38. Ihlamur, M., et al., İlaç Taşıyıcı Sistemler ve Lipozomlar. Kirklareli University Journal of Engineering and Science, 2024. 10(2): p. 207-218.
39. 39. Rahmany, M.B. and M. Van Dyke, Biomimetic approaches to modulate cellular adhesion in biomaterials: A review. Acta Biomater, 2013. 9(3): p. 5431-7.
40. 40. Mei, Y., et al., 3D-Printed Degradable Anti-Tumor Scaffolds for Controllable Drug Delivery. Int J Bioprint, 2021. 7(4): p. 418.
41. 41. Dang, H.P., et al., 3D printed dual macro-, microscale porous network as a tissue engineering scaffold with drug delivering function. Biofabrication, 2019. 11(3): p. 035014.
42. 42. Chittasupho, C., et al., Biopolymer Hydrogel Scaffolds Containing Doxorubicin as A Localized Drug Delivery System for Inhibiting Lung Cancer Cell Proliferation. Polymers (Basel), 2021. 13(20).
43. 43. Dang, P., et al., Local Doxorubicin Delivery via 3D‐Printed Porous Scaffolds Reduces Systemic Cytotoxicity and Breast Cancer Recurrence in Mice. Advanced Therapeutics, 2020. 3: p. 2000056.
44. 44. Dhamaniya, S., V. Gupta, and R. Kakatkar, Recent Advances in Biodegradable Polymers. Journal of Research Updates in Polymer Science, 2018. 7: p. 33-71.
45. 45. Dorati, R., et al., Biodegradable Scaffolds for Bone Regeneration Combined with Drug-Delivery Systems in Osteomyelitis Therapy. Pharmaceuticals (Basel), 2017. 10(4).
46. 46. Kari, V., et al., Gentamicin Loaded PLGA based Biodegradable Material for Controlled Drug Delivery. ChemistrySelect, 2019. 4: p. 8172-8177.
47. 47. Zhou, Z., et al., Antimicrobial Activity of 3D-Printed Poly(ε-Caprolactone) (PCL) Composite Scaffolds Presenting Vancomycin-Loaded Polylactic Acid-Glycolic Acid (PLGA) Microspheres. Med Sci Monit, 2018. 24: p. 6934-6945.
48. 48. Xue, J., et al., Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications. Chem Rev, 2019. 119(8): p. 5298-5415.
49. 49. Mansour, A., et al., Drug Delivery Systems in Regenerative Medicine: An Updated Review. Pharmaceutics, 2023. 15(2).
50. 50. Cámara-Torres, M., et al., 3D additive manufactured composite scaffolds with antibiotic-loaded lamellar fillers for bone infection prevention and tissue regeneration. Bioact Mater, 2021. 6(4): p. 1073-1082.
51. 51. Johnson, C.T. and A.J. García, Scaffold-based anti-infection strategies in bone repair. Ann Biomed Eng, 2015. 43(3): p. 515-28.
52. 52. Rezwan, K., et al., Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials, 2006. 27(18): p. 3413-31.
53. 53. Oliveira É, R., et al., Advances in Growth Factor Delivery for Bone Tissue Engineering. Int J Mol Sci, 2021. 22(2).
54. 54. Rambhia, K.J. and P.X. Ma, Controlled drug release for tissue engineering. J Control Release, 2015. 219: p. 119-128.
55. 55. Cao, H., et al., Fish collagen-based scaffold containing PLGA microspheres for controlled growth factor delivery in skin tissue engineering. Colloids Surf B Biointerfaces, 2015. 136: p. 1098-106.
56. 56. Schugens, C., et al., Biodegradable and macroporous polylactide implants for cell transplantation: 1. Preparation of macroporous polylactide supports by solid-liquid phase separation. Polymer, 1996. 37(6): p. 1027-1038.
57. 57. Yi, S., et al., Extracellular Matrix Scaffolds for Tissue Engineering and Regenerative Medicine. Curr Stem Cell Res Ther, 2017. 12(3): p. 233-246.
58. 58. Zhu, C., et al., A Novel Composite and Suspended Nanofibrous Scaffold for Skin Tissue Engineering. 2018. 1-4.
59. 59. Quinlan, E., et al., Development of collagen-hydroxyapatite scaffolds incorporating PLGA and alginate microparticles for the controlled delivery of rhBMP-2 for bone tissue engineering. J Control Release, 2015. 198: p. 71-9.
60. 60. Lam, J., et al., Evaluation of cell-laden polyelectrolyte hydrogels incorporating poly(L-Lysine) for applications in cartilage tissue engineering. Biomaterials, 2016. 83: p. 332-46.
61. 61. Lee, J.W., et al., Development of a 3D cell printed construct considering angiogenesis for liver tissue engineering. Biofabrication, 2016. 8(1): p. 015007.
62. 62. Rouwkema, J., N.C. Rivron, and C.A. van Blitterswijk, Vascularization in tissue engineering. Trends Biotechnol, 2008. 26(8): p. 434-41.