Juhi Singh, Jacob C Kadir, Jason D Orlando, Stefanie A Sydlik
{"title":"Biomimetic double network hydrogels of chondroitin sulfate and synthetic polypeptides for cartilage tissue engineering.","authors":"Juhi Singh, Jacob C Kadir, Jason D Orlando, Stefanie A Sydlik","doi":"10.1039/d5bm00296f","DOIUrl":null,"url":null,"abstract":"<p><p>Articular cartilage defects are common, and the progressive deterioration of cartilage frequently results in the onset of osteoarthritis. However, the intrinsic regenerative capacity of articular cartilage is minimal. Synthetic therapeutic solutions for treating cartilage damage are being developed. However, current scaffolds and hydrogels employed in cartilage tissue engineering face limitations in promoting cellular activity and providing sufficient load-bearing strength. This is primarily due to suboptimal crosslinking methods for the synthetic scaffolds composed of natural proteins and glycosaminoglycans (GAGs). Synthetic polypeptides, owing to their customizable reactive functional groups, present an exciting opportunity to enhance crosslinking through both physical and chemical approaches. This study introduces a strategy for the development of injectable, shape-adaptive double network hydrogels that closely replicate the structural integrity and mechanical properties of native cartilage. These hydrogels are composed of photocrosslinkable GAGs, specifically methacrylated chondroitin sulfate A (CSMA), combined with a synthetic polypeptide, poly(L-lysine) (PLL). By varying the degree of polymerization (DP) of PLL and weight percentage of PLL in the composition, the hydrogels can be optimized for desired material properties. Varying DP of PLLs varies the molecular weight between crosslinks, thus leading to tunable rigidity (yield strength, ultimate compression strength, storage modulus) and toughness. We further this tunability through the integration of photoresponsive components, enabling controlled, non-invasive post-injection modifications. Initial testing indicates that these double network hydrogels exhibit significantly improved mechanical strength compared to hydrogels formed solely from CSMA, positioning them as strong candidates for minimally invasive cartilage defect repair. This innovative method offers the potential to accelerate recovery, restore joint function, and improve patients' overall quality of life.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials Science","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1039/d5bm00296f","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
Articular cartilage defects are common, and the progressive deterioration of cartilage frequently results in the onset of osteoarthritis. However, the intrinsic regenerative capacity of articular cartilage is minimal. Synthetic therapeutic solutions for treating cartilage damage are being developed. However, current scaffolds and hydrogels employed in cartilage tissue engineering face limitations in promoting cellular activity and providing sufficient load-bearing strength. This is primarily due to suboptimal crosslinking methods for the synthetic scaffolds composed of natural proteins and glycosaminoglycans (GAGs). Synthetic polypeptides, owing to their customizable reactive functional groups, present an exciting opportunity to enhance crosslinking through both physical and chemical approaches. This study introduces a strategy for the development of injectable, shape-adaptive double network hydrogels that closely replicate the structural integrity and mechanical properties of native cartilage. These hydrogels are composed of photocrosslinkable GAGs, specifically methacrylated chondroitin sulfate A (CSMA), combined with a synthetic polypeptide, poly(L-lysine) (PLL). By varying the degree of polymerization (DP) of PLL and weight percentage of PLL in the composition, the hydrogels can be optimized for desired material properties. Varying DP of PLLs varies the molecular weight between crosslinks, thus leading to tunable rigidity (yield strength, ultimate compression strength, storage modulus) and toughness. We further this tunability through the integration of photoresponsive components, enabling controlled, non-invasive post-injection modifications. Initial testing indicates that these double network hydrogels exhibit significantly improved mechanical strength compared to hydrogels formed solely from CSMA, positioning them as strong candidates for minimally invasive cartilage defect repair. This innovative method offers the potential to accelerate recovery, restore joint function, and improve patients' overall quality of life.
期刊介绍:
Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions.