Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the...Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.展开更多
As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-t...As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies,including microfracture,mosaicplasty,autologous chondrocyte implantation(ACI),and matrix-induced ACI(MACI).However,these treatments frequently result in mechanically inferior fibrocartilage,low cost-effectiveness,donor site morbidity,and short-term durability.It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC.Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments.A deeper understanding of the mechanism of endogenous cartilage healing is furthering the(bio)design and application of these scaffolds.Currently,the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells(ESPCs)presents an evolving improvement for cartilage repair.This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration.Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed.The recent advances in novel(bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs(e.g.adhesion,migration,proliferation,differentiation,matrix production,and remodeling)for cartilage repair are summarized.Finally,this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.展开更多
基金supported by grants from the AO Foundation (AOOCD Consortium TA1711481)Areas of Excellence Scheme from the University Grant Council of Hong Kong (Ao E/M-402/20)+1 种基金Theme-based Research Scheme from the University Grant Council of Hong Kong (T13-402/17-N)Key-Area Research and Development Program of Guangdong Province (2019B010941001)
文摘Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.
基金supported by the Areas of Excellence Scheme from University Grant Council of Hong Kong(AoE/M-402/20)the AO Foundation,Switzerland(AO-OCD Consortium TA1711481)+1 种基金the Theme-based Research Scheme from University Grant Council of Hong Kong(T13-402/17-N)the Mainland-Hong Kong Joint Funding Scheme of Innovation and Technology Fund:ITF MHKJFS(MHP/011/20).
文摘As a highly specialized shock-absorbing connective tissue,articular cartilage(AC)has very limited self-repair capacity after traumatic injuries,posing a heavy socioeconomic burden.Common clinical therapies for small-to medium-size focal AC defects are well-developed endogenous repair and cell-based strategies,including microfracture,mosaicplasty,autologous chondrocyte implantation(ACI),and matrix-induced ACI(MACI).However,these treatments frequently result in mechanically inferior fibrocartilage,low cost-effectiveness,donor site morbidity,and short-term durability.It prompts an urgent need for innovative approaches to pattern a pro-regenerative microenvironment and yield hyaline-like cartilage with similar biomechanical and biochemical properties as healthy native AC.Acellular regenerative biomaterials can create a favorable local environment for AC repair without causing relevant regulatory and scientific concerns from cell-based treatments.A deeper understanding of the mechanism of endogenous cartilage healing is furthering the(bio)design and application of these scaffolds.Currently,the utilization of regenerative biomaterials to magnify the repairing effect of joint-resident endogenous stem/progenitor cells(ESPCs)presents an evolving improvement for cartilage repair.This review starts by briefly summarizing the current understanding of endogenous AC repair and the vital roles of ESPCs and chemoattractants for cartilage regeneration.Then several intrinsic hurdles for regenerative biomaterials-based AC repair are discussed.The recent advances in novel(bio)design and application regarding regenerative biomaterials with favorable biochemical cues to provide an instructive extracellular microenvironment and to guide the ESPCs(e.g.adhesion,migration,proliferation,differentiation,matrix production,and remodeling)for cartilage repair are summarized.Finally,this review outlines the future directions of engineering the next-generation regenerative biomaterials toward ultimate clinical translation.