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Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic acid) Composite Matrices

Year 2024, Volume: 52 Issue: 6, 293 - 302, 12.12.2024
https://doi.org/10.15671/hjbc.1528155

Abstract

Currently, analgesics, anti-inflammatory drugs, and hyaluronic acid viscosupplementation are used to alleviate pain associated with joint cartilage disorders. Hyaluronic acid injections are known not only for their pain-reducing effects but also for stimulating cartilage regeneration. In this study, a regenerative biomaterial platform comprising poly (glycolic acid) mesh and cross-linked hyaluronic acid was developed for the repair of degenerated joint cartilage following microfracture and subchondral bone stimulation. For this purpose, in the first stage, hyaluronic acid gels cross-linked with butanediol diglycidyl ether, containing a concentration of 23 mg/mL, were prepared. The residual butanediol diglycidyl ether cross-linker in the obtained gels was below 1 ppb. The pH value was determined to be 6.95 ± 0.2, and the osmolality was 361.3 ± 2.9 mOsm/kg. The injection force and related rheological properties were investigated. In the second stage, the cross-linked hyaluronic acid gels were impregnated into poly (glycolic acid) meshes, evaluated using scanning electron microscopy and characterized chemically. Finally, the composite matrices were recellularized with chondrocytes, and cell viability analysis was conducted using Alamar Blue. The Alamar Blue results and scanning electron microscopy images of the composite structure consisting of poly (glycolic acid) mesh and cross-linked hyaluronic acid indicated that the structure supports chondrocyte viability.

References

  • S.F. Brockmeier, B.S. Shaffer, Viscosupplementation therapy for osteoarthritis, Sports medicine and arthroscopy review, 14 (2006) 155-162.
  • K. Yagishita, I. Sekiya, Y. Sakaguchi, K. Shinomiya, T. Muneta, The effect of hyaluronan on tendon healing in rabbits, Arthroscopy: The Journal of Arthroscopic & Related Surgery, 21 (2005) 1330-1336.
  • M. Wang, Z. Deng, Y. Guo, P. Xu, Designing functional hyaluronic acid-based hydrogels for cartilage tissue engineering, Materials Today Bio, 17 (2022) 100495.
  • A. Serafin, M. Culebras, M.N. Collins, Synthesis and evaluation of alginate, gelatin, and hyaluronic acid hybrid hydrogels for tissue engineering applications, International journal of biological macromolecules, 233 (2023) 123438.
  • B.S. Spearman, N.K. Agrawal, A. Rubiano, C.S. Simmons, S. Mobini, C.E. Schmidt, Tunable methacrylated hyaluronic acid‐based hydrogels as scaffolds for soft tissue engineering applications, Journal of Biomedical Materials Research Part A, 108 (2020) 279-291.
  • I. Onu, R. Gherghel, I. Nacu, F.-D. Cojocaru, L. Verestiuc, D.-V. Matei, D. Cascaval, I.L. Serban, D.A. Iordan, A. Tucaliuc, Can Combining Hyaluronic Acid and Physiotherapy in Knee Osteoarthritis Improve the Physicochemical Properties of Synovial Fluid?, Biomedicines, 12 (2024) 449.
  • J.A. Burdick, G.D. Prestwich, Hyaluronic acid hydrogels for biomedical applications, Advanced materials, 23 (2011) H41-H56.
  • C. Chircov, A.M. Grumezescu, L.E. Bejenaru, Hyaluronic acid-based scaffolds for tissue engineering, Rom. J. Morphol. Embryol, 59 (2018) 71-76.
  • K.L. Spiller, S.A. Maher, A.M. Lowman, Hydrogels for the repair of articular cartilage defects, Tissue engineering part B: reviews, 17 (2011) 281-299.
  • T. Walimbe, A. Panitch, P.M. Sivasankar, A review of hyaluronic acid and hyaluronic acid-based hydrogels for vocal fold tissue engineering, Journal of Voice, 31 (2017) 416-423.
  • A.A. Shimojo, A. Pires, R. Lichy, M.H. Santana, The performance of crosslinking with divinyl sulfone as controlled by the interplay between the chemical modification and conformation of hyaluronic acid, Journal of the Brazilian Chemical Society, 26 (2015) 506-512.
  • S. Ibrahim, Q.K. Kang, A. Ramamurthi, The impact of hyaluronic acid oligomer content on physical, mechanical, and biologic properties of divinyl sulfone‐crosslinked hyaluronic acid hydrogels, Journal of Biomedical Materials Research Part A, 94 (2010) 355-370.
  • M.N. Collins, C. Birkinshaw, Physical properties of crosslinked hyaluronic acid hydrogels, Journal of Materials Science: Materials in Medicine, 19 (2008) 3335-3343.
  • Y. Xue, H. Chen, C. Xu, D. Yu, H. Xu, Y. Hu, Synthesis of hyaluronic acid hydrogels by crosslinking the mixture of high-molecular-weight hyaluronic acid and low-molecular-weight hyaluronic acid with 1,4-butanediol diglycidyl ether, RSC Adv, 10 (2020) 7206-7213.
  • L. Kenne, S. Gohil, E.M. Nilsson, A. Karlsson, D. Ericsson, A.H. Kenne, L.I. Nord, Modification and cross-linking parameters in hyaluronic acid hydrogels—Definitions and analytical methods, Carbohydrate polymers, 91 (2013) 410-418.
  • R. Yang, L. Tan, L. Cen, Z. Zhang, An injectable scaffold based on crosslinked hyaluronic acid gel for tissue regeneration, RSC advances, 6 (2016) 16838-16850.
  • J. Fidalgo, P.-A. Deglesne, R. Arroyo, L. Sepúlveda, E. Ranneva, P. Deprez, Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis, Medical Devices: Evidence and Research, (2018) 367-376.
  • J.-J. Wang, Y.-G. Zhou, Q.-Q. Zhang, J. Zou, Synthesis and properties of novel degradable polyglycolide-based polyurethanes, e-Polymers, 24 (2024).
  • H.S. Park, S.Y. Lee, H. Yoon, I. Noh, Biological evaluation of micro-patterned hyaluronic acid hydrogel for bone tissue engineering, Pure and Applied Chemistry, 86 (2014) 1911-1922.
  • M. Holmes, M. Bayliss, H. Muir, Hyaluronic acid in human articular cartilage. Age-related changes in content and size, Biochemical Journal, 250 (1988) 435-441.
  • D. Rebenda, M. Vrbka, P. Čípek, E. Toropitsyn, D. Nečas, M. Pravda, M. Hartl, On the Dependence of Rheology of Hyaluronic Acid Solutions and Frictional Behavior of Articular Cartilage, Materials, 13 (2020) 2659.
  • P. Bhuanantanondh, D. Grecov, E. Kwok, P. Guy, Rheology of osteoarthritic synovial fluid mixed with viscosupplements: A pilot study, Biomedical Engineering Letters, 1 (2011) 213-219.
  • P. Mathieu, T. Conrozier, E. Vignon, Y. Rozand, M. Rinaudo, Rheologic behavior of osteoarthritic synovial fluid after addition of hyaluronic acid: a pilot study, Clinical Orthopaedics and Related Research®, 467 (2009) 3002-3009.
  • K. De Boulle, R. Glogau, T. Kono, M. Nathan, A. Tezel, J.X. Roca-Martinez, S. Paliwal, D. Stroumpoulis, A review of the metabolism of 1,4-butanediol diglycidyl ether-crosslinked hyaluronic acid dermal fillers, Dermatol Surg, 39 (2013) 1758-1766.
  • K. De Boulle, R. Glogau, T. Kono, M. Nathan, A. Tezel, J.-X. Roca-Martinez, S. Paliwal, D. Stroumpoulis, A review of the metabolism of 1, 4-butanediol diglycidyl ether-crosslinked hyaluronic acid dermal fillers, Dermatologic Surgery, 39 (2013) 1758-1766.
  • H. Barth, S. Crafoord, S. Andréasson, F. Ghosh, A cross-linked hyaluronic acid hydrogel (Healaflow®) as a novel vitreous substitute, Graefe's Archive for Clinical and Experimental Ophthalmology, 254 (2016) 697-703.
  • J. Andrade del Olmo, L. Pérez-Álvarez, V. Sáez Martínez, S. Benito Cid, R. Pérez González, J.L. Vilas-Vilela, J.M. Alonso, Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications, Gels, 8 (2022) 223.
  • S. Kaderli, C. Boulocher, E. Pillet, D. Watrelot-Virieux, A.-L. Rougemont, T. Roger, E. Viguier, R. Gurny, L. Scapozza, O. Jordan, A novel biocompatible hyaluronic acid–chitosan hybrid hydrogel for osteoarthrosis therapy, International journal of pharmaceutics, 483 (2015) 158-168.
  • Y. Lee, S.M. Oh, W. Lee, E.-J. Yang, Comparison of hyaluronic acid filler ejection pressure with injection force for safe filler injection, Journal of Cosmetic Dermatology, 20 (2021) 1551-1556.
  • S. Pierre, S. Liew, A. Bernardin, Basics of dermal filler rheology, Dermatologic surgery, 41 (2015) S120-S126. 31.
  • C.K. Hee, G.T. Shumate, V. Narurkar, A. Bernardin, D.J. Messina, Rheological properties and in vivo performance characteristics of soft tissue fillers, Dermatologic Surgery, 41 (2015) S373-S381.
  • Å. Öhrlund, Factors affecting the rheological measurement of hyaluronic acid gel fillers, Journal of Drugs in Dermatology, 16 (2017) 876-882.
  • B. Lundgren, U. Sandkvist, N. Bordier, B. Gauthier, Using a New Photo Scale to Compare Product Integration of Different Hyaluronan-Based Fillers After Injection in Human Ex Vivo Skin, Journal of drugs in dermatology: JDD, 17 (2018) 982-986.
  • C. de la Guardia, A. Virno, M. Musumeci, A. Bernardin, M.B. Silberberg, Rheologic and physicochemical characteristics of hyaluronic acid fillers: overview and relationship to product performance, Facial Plastic Surgery, 38 (2022) 116-123.
  • G.G.G. Perera, D.F. Argenta, T. Caon, The rheology of injectable hyaluronic acid hydrogels used as facial fillers: A review, International Journal of Biological Macromolecules, 268 (2024) 131880.
  • J.M. Sustaita-Rodriguez, F.J. Medellin-Rodriguez, M. Quintana-Ruiz, O. Davalos-Montoya, A. Rodriguez-Villanueva, E. Ramirez-Vargas, B.S. Hsiao, Synthesis and characterization of poly(glycolic acid) (PGA) and its graphene oxide hybrids (PGA-GO), Polymer Bulletin, 80 (2023) 7741-7761.
  • Y.-C. Wang, M.-C. Lin, D.-M. Wang, H.-J. Hsieh, Fabrication of a novel porous PGA-chitosan hybrid matrix for tissue engineering, Biomaterials, 24 (2003) 1047-1057.

Eklem Kıkırdağı Hasarının Tedavisinde Rejeneratif Materyal: Hyaluronik Asit ve Poli(glikolik asit) Kompozit Matrislerin Sentezi ve Karakterizasyonu

Year 2024, Volume: 52 Issue: 6, 293 - 302, 12.12.2024
https://doi.org/10.15671/hjbc.1528155

Abstract

Günümüzde eklem kıkırdağı bozukluklarıyla ilişkili ağrıyı hafifletmek için analjezikler, anti-inflamatuar ilaçlar ve hyaluronik asit viskosuplementasyonu kullanılmaktadır. Hyaluronik asit enjeksiyonları sadece ağrıyı azaltıcı etkileriyle değil aynı zamanda kıkırdak rejenerasyonunu uyarmasıyla da bilinmektedir. Bu çalışmada, mikro kırık ve subkondral kemik stimülasyonu sonrası dejenerasyona uğramış eklem kıkırdağının onarımı için poli(glikolik asit) ağ ve çapraz bağlı hyaluronik asitten oluşan rejeneratif bir biyomalzeme platformu geliştirilmiştir. Bu amaçla, ilk aşamada 23 mg/mL konsantrasyon içeren bütandiol diglisidil eter ile çapraz bağlı hyaluronik asit jelleri hazırlanmıştır. Elde edilen jellerdeki kalıntı bütandiol diglisidil eter çapraz bağlayıcısı 1 ppb'nin altında elde edilmiştir. pH değeri 6,95 ± 0,2 ve ozmolalite 361,3 ± 2,9 mOsm/kg olarak belirlenmiştir. Enjeksiyon kuvveti ve ilgili reolojik özellikler incelenmiştir. İkinci aşamada, çapraz bağlı hyaluronik asit jelleri poli(glikolik asit) ağlara emdirilmiş, taramalı elektron mikroskobu kullanılarak incelenmiş ve kimyasal olarak karakterize edilmiştir. Son olarak, kompozit matrisler kondrositlerle reselülerize edilmiş ve hücre canlılığı analizi Alamar Blue kullanılarak gerçekleştirilmiştir. Poli(glikolik asit) ağ ve çapraz bağlı hyaluronik asitten oluşan kompozit yapının Alamar Blue sonuçları ve taramalı elektron mikroskobu görüntüleri kompozit yapının kondrosit canlılığını desteklediğini göstermiştir.

References

  • S.F. Brockmeier, B.S. Shaffer, Viscosupplementation therapy for osteoarthritis, Sports medicine and arthroscopy review, 14 (2006) 155-162.
  • K. Yagishita, I. Sekiya, Y. Sakaguchi, K. Shinomiya, T. Muneta, The effect of hyaluronan on tendon healing in rabbits, Arthroscopy: The Journal of Arthroscopic & Related Surgery, 21 (2005) 1330-1336.
  • M. Wang, Z. Deng, Y. Guo, P. Xu, Designing functional hyaluronic acid-based hydrogels for cartilage tissue engineering, Materials Today Bio, 17 (2022) 100495.
  • A. Serafin, M. Culebras, M.N. Collins, Synthesis and evaluation of alginate, gelatin, and hyaluronic acid hybrid hydrogels for tissue engineering applications, International journal of biological macromolecules, 233 (2023) 123438.
  • B.S. Spearman, N.K. Agrawal, A. Rubiano, C.S. Simmons, S. Mobini, C.E. Schmidt, Tunable methacrylated hyaluronic acid‐based hydrogels as scaffolds for soft tissue engineering applications, Journal of Biomedical Materials Research Part A, 108 (2020) 279-291.
  • I. Onu, R. Gherghel, I. Nacu, F.-D. Cojocaru, L. Verestiuc, D.-V. Matei, D. Cascaval, I.L. Serban, D.A. Iordan, A. Tucaliuc, Can Combining Hyaluronic Acid and Physiotherapy in Knee Osteoarthritis Improve the Physicochemical Properties of Synovial Fluid?, Biomedicines, 12 (2024) 449.
  • J.A. Burdick, G.D. Prestwich, Hyaluronic acid hydrogels for biomedical applications, Advanced materials, 23 (2011) H41-H56.
  • C. Chircov, A.M. Grumezescu, L.E. Bejenaru, Hyaluronic acid-based scaffolds for tissue engineering, Rom. J. Morphol. Embryol, 59 (2018) 71-76.
  • K.L. Spiller, S.A. Maher, A.M. Lowman, Hydrogels for the repair of articular cartilage defects, Tissue engineering part B: reviews, 17 (2011) 281-299.
  • T. Walimbe, A. Panitch, P.M. Sivasankar, A review of hyaluronic acid and hyaluronic acid-based hydrogels for vocal fold tissue engineering, Journal of Voice, 31 (2017) 416-423.
  • A.A. Shimojo, A. Pires, R. Lichy, M.H. Santana, The performance of crosslinking with divinyl sulfone as controlled by the interplay between the chemical modification and conformation of hyaluronic acid, Journal of the Brazilian Chemical Society, 26 (2015) 506-512.
  • S. Ibrahim, Q.K. Kang, A. Ramamurthi, The impact of hyaluronic acid oligomer content on physical, mechanical, and biologic properties of divinyl sulfone‐crosslinked hyaluronic acid hydrogels, Journal of Biomedical Materials Research Part A, 94 (2010) 355-370.
  • M.N. Collins, C. Birkinshaw, Physical properties of crosslinked hyaluronic acid hydrogels, Journal of Materials Science: Materials in Medicine, 19 (2008) 3335-3343.
  • Y. Xue, H. Chen, C. Xu, D. Yu, H. Xu, Y. Hu, Synthesis of hyaluronic acid hydrogels by crosslinking the mixture of high-molecular-weight hyaluronic acid and low-molecular-weight hyaluronic acid with 1,4-butanediol diglycidyl ether, RSC Adv, 10 (2020) 7206-7213.
  • L. Kenne, S. Gohil, E.M. Nilsson, A. Karlsson, D. Ericsson, A.H. Kenne, L.I. Nord, Modification and cross-linking parameters in hyaluronic acid hydrogels—Definitions and analytical methods, Carbohydrate polymers, 91 (2013) 410-418.
  • R. Yang, L. Tan, L. Cen, Z. Zhang, An injectable scaffold based on crosslinked hyaluronic acid gel for tissue regeneration, RSC advances, 6 (2016) 16838-16850.
  • J. Fidalgo, P.-A. Deglesne, R. Arroyo, L. Sepúlveda, E. Ranneva, P. Deprez, Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC–MS analysis, Medical Devices: Evidence and Research, (2018) 367-376.
  • J.-J. Wang, Y.-G. Zhou, Q.-Q. Zhang, J. Zou, Synthesis and properties of novel degradable polyglycolide-based polyurethanes, e-Polymers, 24 (2024).
  • H.S. Park, S.Y. Lee, H. Yoon, I. Noh, Biological evaluation of micro-patterned hyaluronic acid hydrogel for bone tissue engineering, Pure and Applied Chemistry, 86 (2014) 1911-1922.
  • M. Holmes, M. Bayliss, H. Muir, Hyaluronic acid in human articular cartilage. Age-related changes in content and size, Biochemical Journal, 250 (1988) 435-441.
  • D. Rebenda, M. Vrbka, P. Čípek, E. Toropitsyn, D. Nečas, M. Pravda, M. Hartl, On the Dependence of Rheology of Hyaluronic Acid Solutions and Frictional Behavior of Articular Cartilage, Materials, 13 (2020) 2659.
  • P. Bhuanantanondh, D. Grecov, E. Kwok, P. Guy, Rheology of osteoarthritic synovial fluid mixed with viscosupplements: A pilot study, Biomedical Engineering Letters, 1 (2011) 213-219.
  • P. Mathieu, T. Conrozier, E. Vignon, Y. Rozand, M. Rinaudo, Rheologic behavior of osteoarthritic synovial fluid after addition of hyaluronic acid: a pilot study, Clinical Orthopaedics and Related Research®, 467 (2009) 3002-3009.
  • K. De Boulle, R. Glogau, T. Kono, M. Nathan, A. Tezel, J.X. Roca-Martinez, S. Paliwal, D. Stroumpoulis, A review of the metabolism of 1,4-butanediol diglycidyl ether-crosslinked hyaluronic acid dermal fillers, Dermatol Surg, 39 (2013) 1758-1766.
  • K. De Boulle, R. Glogau, T. Kono, M. Nathan, A. Tezel, J.-X. Roca-Martinez, S. Paliwal, D. Stroumpoulis, A review of the metabolism of 1, 4-butanediol diglycidyl ether-crosslinked hyaluronic acid dermal fillers, Dermatologic Surgery, 39 (2013) 1758-1766.
  • H. Barth, S. Crafoord, S. Andréasson, F. Ghosh, A cross-linked hyaluronic acid hydrogel (Healaflow®) as a novel vitreous substitute, Graefe's Archive for Clinical and Experimental Ophthalmology, 254 (2016) 697-703.
  • J. Andrade del Olmo, L. Pérez-Álvarez, V. Sáez Martínez, S. Benito Cid, R. Pérez González, J.L. Vilas-Vilela, J.M. Alonso, Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications, Gels, 8 (2022) 223.
  • S. Kaderli, C. Boulocher, E. Pillet, D. Watrelot-Virieux, A.-L. Rougemont, T. Roger, E. Viguier, R. Gurny, L. Scapozza, O. Jordan, A novel biocompatible hyaluronic acid–chitosan hybrid hydrogel for osteoarthrosis therapy, International journal of pharmaceutics, 483 (2015) 158-168.
  • Y. Lee, S.M. Oh, W. Lee, E.-J. Yang, Comparison of hyaluronic acid filler ejection pressure with injection force for safe filler injection, Journal of Cosmetic Dermatology, 20 (2021) 1551-1556.
  • S. Pierre, S. Liew, A. Bernardin, Basics of dermal filler rheology, Dermatologic surgery, 41 (2015) S120-S126. 31.
  • C.K. Hee, G.T. Shumate, V. Narurkar, A. Bernardin, D.J. Messina, Rheological properties and in vivo performance characteristics of soft tissue fillers, Dermatologic Surgery, 41 (2015) S373-S381.
  • Å. Öhrlund, Factors affecting the rheological measurement of hyaluronic acid gel fillers, Journal of Drugs in Dermatology, 16 (2017) 876-882.
  • B. Lundgren, U. Sandkvist, N. Bordier, B. Gauthier, Using a New Photo Scale to Compare Product Integration of Different Hyaluronan-Based Fillers After Injection in Human Ex Vivo Skin, Journal of drugs in dermatology: JDD, 17 (2018) 982-986.
  • C. de la Guardia, A. Virno, M. Musumeci, A. Bernardin, M.B. Silberberg, Rheologic and physicochemical characteristics of hyaluronic acid fillers: overview and relationship to product performance, Facial Plastic Surgery, 38 (2022) 116-123.
  • G.G.G. Perera, D.F. Argenta, T. Caon, The rheology of injectable hyaluronic acid hydrogels used as facial fillers: A review, International Journal of Biological Macromolecules, 268 (2024) 131880.
  • J.M. Sustaita-Rodriguez, F.J. Medellin-Rodriguez, M. Quintana-Ruiz, O. Davalos-Montoya, A. Rodriguez-Villanueva, E. Ramirez-Vargas, B.S. Hsiao, Synthesis and characterization of poly(glycolic acid) (PGA) and its graphene oxide hybrids (PGA-GO), Polymer Bulletin, 80 (2023) 7741-7761.
  • Y.-C. Wang, M.-C. Lin, D.-M. Wang, H.-J. Hsieh, Fabrication of a novel porous PGA-chitosan hybrid matrix for tissue engineering, Biomaterials, 24 (2003) 1047-1057.
There are 37 citations in total.

Details

Primary Language English
Subjects Colloid and Surface Chemistry
Journal Section Articles
Authors

Gülçin Günal 0000-0003-2241-5293

Bengisu Topuz 0000-0001-6698-5154

Halil Murat Aydın 0000-0003-4107-4324

Publication Date December 12, 2024
Submission Date August 5, 2024
Acceptance Date November 25, 2024
Published in Issue Year 2024 Volume: 52 Issue: 6

Cite

APA Günal, G., Topuz, B., & Aydın, H. M. (2024). Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic acid) Composite Matrices. Hacettepe Journal of Biology and Chemistry, 52(6), 293-302. https://doi.org/10.15671/hjbc.1528155
AMA Günal G, Topuz B, Aydın HM. Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic acid) Composite Matrices. HJBC. December 2024;52(6):293-302. doi:10.15671/hjbc.1528155
Chicago Günal, Gülçin, Bengisu Topuz, and Halil Murat Aydın. “Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic Acid) Composite Matrices”. Hacettepe Journal of Biology and Chemistry 52, no. 6 (December 2024): 293-302. https://doi.org/10.15671/hjbc.1528155.
EndNote Günal G, Topuz B, Aydın HM (December 1, 2024) Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic acid) Composite Matrices. Hacettepe Journal of Biology and Chemistry 52 6 293–302.
IEEE G. Günal, B. Topuz, and H. M. Aydın, “Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic acid) Composite Matrices”, HJBC, vol. 52, no. 6, pp. 293–302, 2024, doi: 10.15671/hjbc.1528155.
ISNAD Günal, Gülçin et al. “Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic Acid) Composite Matrices”. Hacettepe Journal of Biology and Chemistry 52/6 (December 2024), 293-302. https://doi.org/10.15671/hjbc.1528155.
JAMA Günal G, Topuz B, Aydın HM. Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic acid) Composite Matrices. HJBC. 2024;52:293–302.
MLA Günal, Gülçin et al. “Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic Acid) Composite Matrices”. Hacettepe Journal of Biology and Chemistry, vol. 52, no. 6, 2024, pp. 293-02, doi:10.15671/hjbc.1528155.
Vancouver Günal G, Topuz B, Aydın HM. Regenerative Material for the Treatment of Articular Cartilage Damage: Synthesis and Characterization of Hyaluronic Acid and Poly(glycolic acid) Composite Matrices. HJBC. 2024;52(6):293-302.

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