RESUMO
Despite numerous studies on chondrogenesis, the repair of cartilage-particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-ß3 (TGF-ß3) into mesoporous silica nanoparticles (MSNs). Then, TGF-ß3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@µS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-ß3 amplified chondrogenesis and matrix formation. µS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.
RESUMO
Background: The utilization of decellularized extracellular matrix has gained considerable attention across numerous areas in regenerative research. Of particular interest is the human articular cartilage-derived extracellular matrix (hACECM), which presents as a promising facilitator for cartilage regeneration. Concurrently, the microfracture (MF) âtechnique, a well-established marrow stimulation method, has proven efficacious in the repair of cartilage defects. However, as of the current literature review, no investigations have explored the potential of a combined application of hACECM and the microfracture technique in the repair of cartilage defects within a sheep model. Hypothesis: The combination of hACECM scaffold and microfracture will result in improved repair of full-thickness femoral condyle articular cartilage defects compared to the use of either technique alone. Study design: Controlled laboratory study. Methods: Full-thickness femoral condyle articular cartilage defect (diameter, 7.0 âmm; debrided down to the subchondral bone plate) were created in the weight-bearing area of the femoral medial and lateral condyles (n â= â24). All of defected sheep were randomly divided into four groups: control, microfracture, hACECM scaffold, and hACECM scaffold â+ âmicrofracture. After 3, 6 and 12 months, the chondral repair was assessed for standardized (semi-) quantitative macroscopic, imaging, histological, immunohistochemical, mechanics, and biochemical analyses in each group. Result: At 3, 6 and 12 months after implantation, the gross view and pathological staining of regenerative tissues were better in the hACECM scaffold and hACECM scaffold â+ âmicrofracture groups than in the microfracture and control groups; Micro-CT result showed that the parameters about the calcified layer of cartilage and subchondral bone were better in the hACECM scaffold and hACECM scaffold â+ âmicrofracture groups than the others, and excessive subchondral bone proliferation in the microfracture group. The results demonstrate that human cartilage extracellular matrix scaffold alone is an efficient, safe and simple way to repair cartilage defects. Conclusion: hACECM scaffolds combined with/without microfracture facilitate chondral defect repair. The translational potential of this article: Preclinical large animal models represent an important adjunct and surrogate for studies on articular cartilage repair, while the sheep stifle joint reflects many key features of the human knee and are therefore optimal experimental model for future clinical application in human. In this study, we developed a human articular cartilage-derived extracellular matrix scaffold and to verify the viability of its use in sheep animal models. Clinical studies are warranted to further quantify the effects of hACECM scaffolds in similar settings.
RESUMO
The self-repair ability of cartilage defects is limited, and 3D printing technology provides hope for the repair and regeneration of cartilage defects. Although 3D printing technology and cartilage repair and regeneration have been studied for decades, there are still few articles specifically describing the relationship between 3D printing and cartilage defect repair and regeneration, and a bibliometric analysis has not been completed. To supplement, sort out and summarize the content in related fields, we analyzed the research status of 3D printing technology and cartilage repair and regeneration from 2002 to 2022. According to the set search strategy, the Web of Science Core Collection was used as the data source, and the literature search was completed on December 6, 2022. CiteSpace V and VOSviewer were used as bibliometric tools to complete the analysis of the research focus and direction of the published literature. Based on the analysis results, we focus on the occurrence and development of this field of combined medical and engineering research. Moreover, the current advantages and limitations of this field as well as future development prospects are discussed in depth. It will help to shape researchers' understanding of 3D printing and cartilage repair and regeneration, inspire researchers' research ideas, guide research directions, and promote related research results to clinical application.