The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs...The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs were used. The right knee underwent mosaicplasty with tissue-engineered cartilage for treatment of focal osteochondral defects, while the left knee was repaired via single mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue was evaluated by magnetic resonance imaging (MRI) with the cartilage repair tissue (MOCART) scoring system and T2 mapping. Then, the results of MRI for 26 weeks were compared with findings of macroscopic and histologic studies. The MOCART scores showed that the repaired tissue of the tissue-engineered cartilage group was statistically better than that of controls (P 〈 0.001). A significant correlation was found between macroscopic and MOCART scores (P 〈 0.001). Comparable mean T2 values were found between adjacent cartilage and repair tissue in the experimental group (P 〉 0.05). For zonal T2 value evaluation, there were no significant zonal T2 differences for repair tissue in controls (P 〉 0.05). For the experimental group, zonal T2 variation was found in repair tissue (P 〈 0.05). MRI, macroscopy and histology showed better repair results and bony incorporation in mosaicplasty with the tissue-engi- neered cartilage group than those of the single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a promising approach to repair osteochodndral defects. Morphological MRI and T2 mapping provide a non-invasive method for monitoring the maturation and integration of cartilage repair tissue in vivo.展开更多
In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide...In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAAm-g-HA) has been synthesized as an injectable scaffold for cartilage tissue engineering. The aim of this study was to investigate the efficacy and cytocompatibility of PNIPAAm-g-HA to normal chondrocytes by using reverse transcription-polymerase chain reaction (RT-PCR) analysis and histochemical staining in preliminary in vitro and in vitro experiments. Hematoxylin and eosin staining showed homogeneous distribution of cells in the PNIPAAm-g-HA hydrogel in 3-dimensional in vitro cultivation. Alcian blue staining also indicated that abundant extracellular matrix formation, including acidic glycosaminoglycans, occurred in tissue-engineered cartilage over time in vitro. Cartilage-related gene expression patterns, which were tested in rabbit normal chondrocytes embedded in the hydrogel, were almost maintained for 4 weeks. Transforming growth factor-β1 (TGF-β1) stimulation enhanced the expression of SRY-related HMG box-containing gene 9 (Sox9) and type X collagen genes suggesting promotion of chondrogenic differentiation. Histochemical evaluation showed neocartilage formation following subcutaneous implantation of the chondrocyte-gel mixture in nude mice. Furthermore, TGF-β1 stimulation promoted production and maturation of the extracellular matrix of the in situ tissue engineered hyaline cartilage. These data suggested that PNIPAAm-g-HA could be a promising biomaterial, i.e., a self-assembling and injectable scaffold for cartilage tissue engineering.展开更多
For regenerative medicine, clarification of in vivo migration of transplanted cells is an important task to secure the safety of transplanted tissue. We had prepared tissue-engineered cartilage consisting of cultured ...For regenerative medicine, clarification of in vivo migration of transplanted cells is an important task to secure the safety of transplanted tissue. We had prepared tissue-engineered cartilage consisting of cultured chondrocytes with collagen hydrogel and a biodegradable porous polymer, and we clinically applied it for treatment of craniofacial anomaly. To verify the safety of this tissue-engineered cartilage, we had syngenically transplanted the tissue-engineered cartilage using chondrocytes harvested from EGFP-transgenic mice into subcutaneous pocket of wild type mice, and investigated localizations of transplanted chondrocytes in various organs including cerebrum, lung, liver, spleen, kidney, auricle, gastrocnemius, and femur. After 8 to 24 weeks of the transplantation, accumulation of cartilaginous matrices was observed in tissue-engineered cartilage, while EGFP-positive transplanted chondrocytes were localized in this area. Otherwise, no EGFP was immunohistochemically detected in each organ, suggesting that subcutaneously-transplanted chondrocytes do not migrate to other organs through the circulation. In cartilage tissue engineering using cultured chondrocytes, risk for migration and circulation of transplanted cells seemed negligible, and that ectopic growth of the cells was unlikely to occur, showing that this is safe technique with regard to the in vivo migration of transplanted cells.展开更多
The efficiency of substance exchange may be decreased when the thickness and volume of such a tissue-engineered cartilage that is composed of cultured cells and porous scaffold increase. Moreover, during the transport...The efficiency of substance exchange may be decreased when the thickness and volume of such a tissue-engineered cartilage that is composed of cultured cells and porous scaffold increase. Moreover, during the transport of this construct with complicated shapes, excessive and focal mechanical loading may cause deformation. The establishment of incubation and transport methods is necessary for the three-dimensional tissue-engineered cartilage. Therefore, we investigated the preparation of an agarose mold with a concavity similar to the shape of 3-dimensional tissue-engineered cartilage to prevent excessive and focal concentration of stress, while avoiding interference with substance exchange as much as possible. Firstly, we investigated the preparation at 1% - 4% agarose concentrations. Since the mechanical strength was insufficient at 1%, 2% was regarded as appropriate. Using 2% agarose, we prepared a mold with a 5 × 5 × 5 mm concavity to accommodate tissue-engineered cartilage (5 × 5 × 5 mm mixture of 1.5 × 107 cells and collagen gel), and stored the regenerative cartilage in it for 2 and 24 hours. On comparison with storage in a plastic mold with the same shape in which substance exchanged from side and bottom was impossible, although no significant differences were noted in the number or viability of cells after 2 hours, these were markedly reduced in the plastic mold after 24 hours. It was confirmed that favorable cell numbers and viability were maintained by immediately retaining the regenerative cartilage in the culture medium in the agarose mold and keeping the temperature at 37°C. Since this agarose mold also buffers against mechanical forces loaded on the three-dimensional regenerative tissue, it may be useful as a container for storage and transport of large-sized three-dimensional regenerative tissue.展开更多
Hyaline cartilage plays a critical role in maintaining joint function and pain.However,the lack of blood supply,nerves,and lymphatic vessels greatly limited the self-repair and regeneration of damaged cartilage,giving...Hyaline cartilage plays a critical role in maintaining joint function and pain.However,the lack of blood supply,nerves,and lymphatic vessels greatly limited the self-repair and regeneration of damaged cartilage,giving rise to various tricky issues in medicine.In the past 30 years,numerous treatment techniques and commercial products have been developed and practiced in the clinic for promoting defected cartilage repair and regeneration.Here,the current therapies and their relevant advantages and disadvantages will be summarized,particularly the tissue engineering strategies.Furthermore,the fabrication of tissue-engineered cartilage under research or in the clinic was discussed based on the traid of tissue engineering,that is the materials,seed cells,and bioactive factors.Finally,the commercialized cartilage repair products were listed and the regulatory issues and challenges of tissue-engineered cartilage repair products and clinical application would be reviewed.展开更多
BACKGROUND This case report highlights a rare instance of concurrent keloid and epidermal cyst development at an ear cartilage harvest site following rhinoplasty in a 25-year-old woman.Both conditions,which typically ...BACKGROUND This case report highlights a rare instance of concurrent keloid and epidermal cyst development at an ear cartilage harvest site following rhinoplasty in a 25-year-old woman.Both conditions,which typically stem from skin trauma,seldom occur together,demonstrating the exceptional characteristics of this case.CASE SUMMARY The patient underwent successful surgical removal of both the keloid and the epidermal cyst.Postoperative treatment included the use of silicone sheets,gel,and oral tranilast to reduce scarring.No recurrence was observed over a 6-mo follow-up period,indicating effective management of the condition.CONCLUSION The effective management of complex skin trauma cases underscores the need for individualized treatment strategies in plastic surgery.展开更多
BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate ...BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate magnetic resonance imaging(MRI)multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury.METHODS A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study.We analyzed the accuracy of conventional MRI sequences(T1-weighted imaging,T2-weighted imaging,proton density weighted imaging,and T2 star weighted image)and Three-Dimensional Coronary Imaging by Spiral Scanning(3D-CISS)in the diagnosis of elbow cartilage injury.Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy.RESULTS The diagnostic accuracy of 3D-CISS sequence was 89.34%±4.98%,the sensitivity was 90%,and the specificity was 88.33%,which showed the best performance among all sequences(P<0.05).The combined application of the whole sequence had the highest accuracy in all sequence combinations,the accuracy of mild injury was 91.30%,the accuracy of moderate injury was 96.15%,and the accuracy of severe injury was 93.33%(P<0.05).Compared with arthroscopy,the combination of all MRI sequences had the highest consistency of 91.67%,and the kappa value reached 0.890(P<0.001).CONCLUSION Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults.Multisequence MRI is recommended to ensure the best diagnosis and treatment.展开更多
BACKGROUND Endoscopic ear surgery(EES)provides a magnified,high-definition view of the otological surgical field.EES allows otologists to avoid surgical incisions and associated postoperative complications.It is an id...BACKGROUND Endoscopic ear surgery(EES)provides a magnified,high-definition view of the otological surgical field.EES allows otologists to avoid surgical incisions and associated postoperative complications.It is an ideal technique for the perfor-mance and teaching of tympanoplasty.AIM To examine the efficacy of total Endoscopic Push Through Tragal Cartilage Tympanoplasty(EPTTCT),at our institution over a 10-year period.METHODS A retrospective analysis of 168 cases of EPTTCT for closure of small to medium tympanic membrane perforations from 2013-2023 was conducted.Patient sex,age range(pediatric vs adult),etiology of injury,success rate,complications,and postoperative hearing status were collected.RESULTS Graft uptake results indicated success in 94%of patients,with less than a 2%complication rate.Postoperative pure tone audiometry demonstrated hearing status improvement in 69%of patients.CONCLUSION EPTTCT has been shown to be effective in tympanic membrane perforation closures with minimal complications.This study further demonstrates the efficacy and safety of these procedures in a single-center review.展开更多
The relentless pain and disability caused by osteoarthritis stem from the body’s own cartilage cells going rogue under inflammatory conditions.They secrete enzymes that devour the cushioning cartilage matrix,leading ...The relentless pain and disability caused by osteoarthritis stem from the body’s own cartilage cells going rogue under inflammatory conditions.They secrete enzymes that devour the cushioning cartilage matrix,leading to joint damage.Conventional drugs cannot effectively reach this inflammatory source within the dense cartilage.展开更多
Human placenta-derived stem cells (hPDSCs) were isolated by trypsinization and further induced into cartilage cells in vitro.The engineered cartilage was constructed by combining hPDSCs with collagen sponge and the ca...Human placenta-derived stem cells (hPDSCs) were isolated by trypsinization and further induced into cartilage cells in vitro.The engineered cartilage was constructed by combining hPDSCs with collagen sponge and the cartilage formation was observed by implantation into nude mice.Results showed that hPDSCs featured mesenchymal stem cells and maintained proliferation in vitro for over 30 passages while remaining undifferentiated.All results indicated that hPDSCs have the potential to differentiate into functional cartilage cells in vitro when combined with collagen sponge,which provided experimental evidence for prospective clinical application.展开更多
The limited ability of cartilage tissue to repair itself poses a functionally impairing health problem. While many treatment methods are available, full restoration of the tissue to its original state is rare. Often, ...The limited ability of cartilage tissue to repair itself poses a functionally impairing health problem. While many treatment methods are available, full restoration of the tissue to its original state is rare. Often, complete joint replacement surgery is required to obtain long-term relief. Tissue engineering approaches, however, provide new opportunities for cartilage replacement. They seek to provide mechanisms to repair or replace lost tissue or function. A theoretical method is presented here for regenerating hyaline cartilage in vitro using a chondrocyte-seeded three-dimensional biomimetic engineered scaffold with mechanical properties similar to those occurring naturally. The scaffold composition, type II collagen, aggrecan, hyaluronan, hyaluronan binding protein (for link protein), and BMP-7, were chosen to encourage synthesis of hyaline cartilage by providing a more native environment and signaling cue for the seeded chondrocytes. The scaffold components mimic the macrofibrillar collagen network found in articular cartilage. Type II collagen provides tensile strength, and aggrecan, the predominant proteoglycan, provides compressive strength.展开更多
Articular cartilage serves as a low-friction,load-bearing tissue without the support with blood vessels,lymphatics and nerves,making its repair a big challenge.Transforming growth factor-beta 3(TGF-β3),a vital member...Articular cartilage serves as a low-friction,load-bearing tissue without the support with blood vessels,lymphatics and nerves,making its repair a big challenge.Transforming growth factor-beta 3(TGF-β3),a vital member of the highly conserved TGF-βsuperfamily,plays a versatile role in cartilage physiology and pathology.TGF-β3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses,including cell survival,proliferation,migration,and differentiation.Since TGF-β3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy,its regulatory role is especially important to cartilage development.Increased TGF-β3 plays a dual role:in healthy tissues,it can facilitate chondrocyte viability,but in osteoarthritic chondrocytes,it can accelerate the progression of disease.Recently,TGF-β3 has been recognized as a potential therapeutic target for osteoarthritis(OA)owing to its protective effect,which it confers by enhancing the recruitment of autologous mesenchymal stem cells(MSCs)to damaged cartilage.However,the biological mechanism of TGF-β3 action in cartilage development and OA is not well understood.In this review,we systematically summarize recent progress in the research on TGF-β3 in cartilage physiology and pathology,providing up-to-date strategies for cartilage repair and preventive treatment.展开更多
Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor a...Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.展开更多
The anterior disc displacement(ADD)leads to temporomandibular joint osteoarthritis(TMJOA)and mandibular growth retardation in adolescents.To investigate the potential functional role of fibrocartilage stem cells(FCSCs...The anterior disc displacement(ADD)leads to temporomandibular joint osteoarthritis(TMJOA)and mandibular growth retardation in adolescents.To investigate the potential functional role of fibrocartilage stem cells(FCSCs)during the process,a surgical ADDTMJOA mouse model was established.From 1 week after model generation,ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis(OA)-like joint cartilage degeneration,manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis.Lineage tracing using Gli1^(-)CreER^(+);Tm^(fl/-)mice and Sox9-CreER^(+);Tm^(fl/-)mice showed that ADD interfered with the chondrogenic capacity of Gli1+FCSCs as well as osteogenic differentiation of Sox9+lineage,mainly in the middle zone of TMJ cartilage.Then,a surgically induced disc reposition(DR)mouse model was generated.The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice.And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment.In conclusion,ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage,resulting in cartilage degeneration and loss of subchondral bone homeostasis,finally causing TMJ growth retardation.DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.展开更多
This study is designed to determine whether the outermost layer of articular cartilage is deficient in Osteoarthritis (OA). Phospholipids present in healthy and osteoarthritis (OA) synovial fluid show significant diff...This study is designed to determine whether the outermost layer of articular cartilage is deficient in Osteoarthritis (OA). Phospholipids present in healthy and osteoarthritis (OA) synovial fluid show significant differences in their concentration. While examining the surface properties of OA joints, we found that OA PLs molecules cannot support lubrication, and increased friction was observed. Our lubrication mechanism was based on a surface active phospholipids (SAPL) multibilayer which in OA condition was deactivated and removed from the cartilage surface under OA conditions. Cartilage wettability study clearly demonstrated a significant decrease in hydrophobicity, the contact angle, θ (theta), dropping from 103° from bovine healthy cartilage to 65° in surface partially depleted and 35.1° for completely depleted surface. These results are discussed in the context that surface active phospholipid (SAPL) and lubricin, each has specific roles in a lamellar-repulsive lubrication system. However, deactivated phospholipid molecules are major indicator of cartilage wear (model) introduced in this study.展开更多
Cartilage is a nonedible byproduct with little saleable value.However,previous studies have proposed the possibility of producing peptides from cartilage with immune function modulation potential.The current study aim...Cartilage is a nonedible byproduct with little saleable value.However,previous studies have proposed the possibility of producing peptides from cartilage with immune function modulation potential.The current study aimed to investigate the potential anti-inflammatory activity of peptides derived from sturgeon(Acipenser schrenckii)cartilage in lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.Five peptide sequences,including four novel peptides,were identified from ethanol-soluble cartilage hydrolysates.Among these five peptides,LTGP,LLLE,LLEL and VGPAGPAGP reduced the production of nitric oxide(NO)and interleukin-6(IL-6)while increasing interleukin-10(IL-10)excretion.Transcriptome analysis suggested the inhibition of activated mitogen-activated protein kinase(MAPK)and interleukin-17(IL-17)signaling pathways after LLEL intervention.MAPK,which is involved in the IL-17 signaling pathway,was further proved to be blocked by downregulating the phosphorylation of p38,extracellular-signal regulated protein kinase(ERK),and c-jun N-terminal kinase(JNK).This novel peptide offers an attractive approach to develop functional foods.展开更多
Articular cartilage damage caused by trauma or degenerative pathologies such as osteoarthritis can result in significant pain,mobility issues,and disability.Current surgical treatments have a limited capacity for effi...Articular cartilage damage caused by trauma or degenerative pathologies such as osteoarthritis can result in significant pain,mobility issues,and disability.Current surgical treatments have a limited capacity for efficacious cartilage repair,and long-term patient outcomes are not satisfying.Three-dimensional bioprinting has been used to fabricate biochemical and biophysical environments that aim to recapitulate the native microenvironment and promote tissue regeneration.However,conventional in vitro bioprinting has limitations due to the challenges associated with the fabrication and implantation of bioprinted constructs and their integration with the native cartilage tissue.In situ bioprinting is a novel strategy to directly deliver bioinks to the desired anatomical site and has the potential to overcome major shortcomings associated with conventional bioprinting.In this review,we focus on the new frontier of robotic-assisted in situ bioprinting surgical systems for cartilage regeneration.We outline existing clinical approaches and the utilization of robotic-assisted surgical systems.Handheld and robotic-assisted in situ bioprinting techniques including minimally invasive and non-invasive approaches are defined and presented.Finally,we discuss the challenges and potential future perspectives of in situ bioprinting for cartilage applications.展开更多
At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional...At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic implants.This study explored the combination of 3D printing and tissue engineering to precisely reconstruct the auricle.First,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle reconstruction.In vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage fragments.In vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle reconstruction.The results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in vitro.After three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in vivo.The autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.展开更多
Due to the limited self healing capacity of human cartilage,the repair of defects gives rise to a challenging clinical problem.Cartilage tissue engineering provides a new method to solve cartilage repair.However,the s...Due to the limited self healing capacity of human cartilage,the repair of defects gives rise to a challenging clinical problem.Cartilage tissue engineering provides a new method to solve cartilage repair.However,the search for a suitable biological vector material has long been the focus of research interest in this regard.In this paper,the present situation of cartilage tissue engineering vector materials is reviewed.展开更多
基金supported by the National Natural Science Foundation ofChina(No.81000800)
文摘The aim of this study was to evaluate the efficacy of mosaicplasty with tissue-engineered cartilage for the treatment of osteochondral defects in a pig model with advanced MR technique. Eight adolescent miniature pigs were used. The right knee underwent mosaicplasty with tissue-engineered cartilage for treatment of focal osteochondral defects, while the left knee was repaired via single mosaicplasty as controls. At 6, 12, 18 and 26 weeks after surgery, repair tissue was evaluated by magnetic resonance imaging (MRI) with the cartilage repair tissue (MOCART) scoring system and T2 mapping. Then, the results of MRI for 26 weeks were compared with findings of macroscopic and histologic studies. The MOCART scores showed that the repaired tissue of the tissue-engineered cartilage group was statistically better than that of controls (P 〈 0.001). A significant correlation was found between macroscopic and MOCART scores (P 〈 0.001). Comparable mean T2 values were found between adjacent cartilage and repair tissue in the experimental group (P 〉 0.05). For zonal T2 value evaluation, there were no significant zonal T2 differences for repair tissue in controls (P 〉 0.05). For the experimental group, zonal T2 variation was found in repair tissue (P 〈 0.05). MRI, macroscopy and histology showed better repair results and bony incorporation in mosaicplasty with the tissue-engi- neered cartilage group than those of the single mosaicplasty group. Mosaicplasty with the tissue-engineered cartilage is a promising approach to repair osteochodndral defects. Morphological MRI and T2 mapping provide a non-invasive method for monitoring the maturation and integration of cartilage repair tissue in vivo.
文摘In order to contribute to the development of minimally invasive surgery techniques for autologous chondrocyte implantation, a novel self-assembling biomaterial consisting of thermoresponsive poly(N-isopropylacrylamide)-grafted hyaluronan (PNIPAAm-g-HA) has been synthesized as an injectable scaffold for cartilage tissue engineering. The aim of this study was to investigate the efficacy and cytocompatibility of PNIPAAm-g-HA to normal chondrocytes by using reverse transcription-polymerase chain reaction (RT-PCR) analysis and histochemical staining in preliminary in vitro and in vitro experiments. Hematoxylin and eosin staining showed homogeneous distribution of cells in the PNIPAAm-g-HA hydrogel in 3-dimensional in vitro cultivation. Alcian blue staining also indicated that abundant extracellular matrix formation, including acidic glycosaminoglycans, occurred in tissue-engineered cartilage over time in vitro. Cartilage-related gene expression patterns, which were tested in rabbit normal chondrocytes embedded in the hydrogel, were almost maintained for 4 weeks. Transforming growth factor-β1 (TGF-β1) stimulation enhanced the expression of SRY-related HMG box-containing gene 9 (Sox9) and type X collagen genes suggesting promotion of chondrogenic differentiation. Histochemical evaluation showed neocartilage formation following subcutaneous implantation of the chondrocyte-gel mixture in nude mice. Furthermore, TGF-β1 stimulation promoted production and maturation of the extracellular matrix of the in situ tissue engineered hyaline cartilage. These data suggested that PNIPAAm-g-HA could be a promising biomaterial, i.e., a self-assembling and injectable scaffold for cartilage tissue engineering.
文摘For regenerative medicine, clarification of in vivo migration of transplanted cells is an important task to secure the safety of transplanted tissue. We had prepared tissue-engineered cartilage consisting of cultured chondrocytes with collagen hydrogel and a biodegradable porous polymer, and we clinically applied it for treatment of craniofacial anomaly. To verify the safety of this tissue-engineered cartilage, we had syngenically transplanted the tissue-engineered cartilage using chondrocytes harvested from EGFP-transgenic mice into subcutaneous pocket of wild type mice, and investigated localizations of transplanted chondrocytes in various organs including cerebrum, lung, liver, spleen, kidney, auricle, gastrocnemius, and femur. After 8 to 24 weeks of the transplantation, accumulation of cartilaginous matrices was observed in tissue-engineered cartilage, while EGFP-positive transplanted chondrocytes were localized in this area. Otherwise, no EGFP was immunohistochemically detected in each organ, suggesting that subcutaneously-transplanted chondrocytes do not migrate to other organs through the circulation. In cartilage tissue engineering using cultured chondrocytes, risk for migration and circulation of transplanted cells seemed negligible, and that ectopic growth of the cells was unlikely to occur, showing that this is safe technique with regard to the in vivo migration of transplanted cells.
文摘The efficiency of substance exchange may be decreased when the thickness and volume of such a tissue-engineered cartilage that is composed of cultured cells and porous scaffold increase. Moreover, during the transport of this construct with complicated shapes, excessive and focal mechanical loading may cause deformation. The establishment of incubation and transport methods is necessary for the three-dimensional tissue-engineered cartilage. Therefore, we investigated the preparation of an agarose mold with a concavity similar to the shape of 3-dimensional tissue-engineered cartilage to prevent excessive and focal concentration of stress, while avoiding interference with substance exchange as much as possible. Firstly, we investigated the preparation at 1% - 4% agarose concentrations. Since the mechanical strength was insufficient at 1%, 2% was regarded as appropriate. Using 2% agarose, we prepared a mold with a 5 × 5 × 5 mm concavity to accommodate tissue-engineered cartilage (5 × 5 × 5 mm mixture of 1.5 × 107 cells and collagen gel), and stored the regenerative cartilage in it for 2 and 24 hours. On comparison with storage in a plastic mold with the same shape in which substance exchanged from side and bottom was impossible, although no significant differences were noted in the number or viability of cells after 2 hours, these were markedly reduced in the plastic mold after 24 hours. It was confirmed that favorable cell numbers and viability were maintained by immediately retaining the regenerative cartilage in the culture medium in the agarose mold and keeping the temperature at 37°C. Since this agarose mold also buffers against mechanical forces loaded on the three-dimensional regenerative tissue, it may be useful as a container for storage and transport of large-sized three-dimensional regenerative tissue.
文摘Hyaline cartilage plays a critical role in maintaining joint function and pain.However,the lack of blood supply,nerves,and lymphatic vessels greatly limited the self-repair and regeneration of damaged cartilage,giving rise to various tricky issues in medicine.In the past 30 years,numerous treatment techniques and commercial products have been developed and practiced in the clinic for promoting defected cartilage repair and regeneration.Here,the current therapies and their relevant advantages and disadvantages will be summarized,particularly the tissue engineering strategies.Furthermore,the fabrication of tissue-engineered cartilage under research or in the clinic was discussed based on the traid of tissue engineering,that is the materials,seed cells,and bioactive factors.Finally,the commercialized cartilage repair products were listed and the regulatory issues and challenges of tissue-engineered cartilage repair products and clinical application would be reviewed.
文摘BACKGROUND This case report highlights a rare instance of concurrent keloid and epidermal cyst development at an ear cartilage harvest site following rhinoplasty in a 25-year-old woman.Both conditions,which typically stem from skin trauma,seldom occur together,demonstrating the exceptional characteristics of this case.CASE SUMMARY The patient underwent successful surgical removal of both the keloid and the epidermal cyst.Postoperative treatment included the use of silicone sheets,gel,and oral tranilast to reduce scarring.No recurrence was observed over a 6-mo follow-up period,indicating effective management of the condition.CONCLUSION The effective management of complex skin trauma cases underscores the need for individualized treatment strategies in plastic surgery.
文摘BACKGROUND Due to frequent and high-risk sports activities,the elbow joint is susceptible to injury,especially to cartilage tissue,which can cause pain,limited movement and even loss of joint function.AIM To evaluate magnetic resonance imaging(MRI)multisequence imaging for improving the diagnostic accuracy of adult elbow cartilage injury.METHODS A total of 60 patients diagnosed with elbow cartilage injury in our hospital from January 2020 to December 2021 were enrolled in this retrospective study.We analyzed the accuracy of conventional MRI sequences(T1-weighted imaging,T2-weighted imaging,proton density weighted imaging,and T2 star weighted image)and Three-Dimensional Coronary Imaging by Spiral Scanning(3D-CISS)in the diagnosis of elbow cartilage injury.Arthroscopy was used as the gold standard to evaluate the diagnostic effect of single and combination sequences in different injury degrees and the consistency with arthroscopy.RESULTS The diagnostic accuracy of 3D-CISS sequence was 89.34%±4.98%,the sensitivity was 90%,and the specificity was 88.33%,which showed the best performance among all sequences(P<0.05).The combined application of the whole sequence had the highest accuracy in all sequence combinations,the accuracy of mild injury was 91.30%,the accuracy of moderate injury was 96.15%,and the accuracy of severe injury was 93.33%(P<0.05).Compared with arthroscopy,the combination of all MRI sequences had the highest consistency of 91.67%,and the kappa value reached 0.890(P<0.001).CONCLUSION Combination of 3D-CISS and each sequence had significant advantages in improving MRI diagnostic accuracy of elbow cartilage injuries in adults.Multisequence MRI is recommended to ensure the best diagnosis and treatment.
文摘BACKGROUND Endoscopic ear surgery(EES)provides a magnified,high-definition view of the otological surgical field.EES allows otologists to avoid surgical incisions and associated postoperative complications.It is an ideal technique for the perfor-mance and teaching of tympanoplasty.AIM To examine the efficacy of total Endoscopic Push Through Tragal Cartilage Tympanoplasty(EPTTCT),at our institution over a 10-year period.METHODS A retrospective analysis of 168 cases of EPTTCT for closure of small to medium tympanic membrane perforations from 2013-2023 was conducted.Patient sex,age range(pediatric vs adult),etiology of injury,success rate,complications,and postoperative hearing status were collected.RESULTS Graft uptake results indicated success in 94%of patients,with less than a 2%complication rate.Postoperative pure tone audiometry demonstrated hearing status improvement in 69%of patients.CONCLUSION EPTTCT has been shown to be effective in tympanic membrane perforation closures with minimal complications.This study further demonstrates the efficacy and safety of these procedures in a single-center review.
文摘The relentless pain and disability caused by osteoarthritis stem from the body’s own cartilage cells going rogue under inflammatory conditions.They secrete enzymes that devour the cushioning cartilage matrix,leading to joint damage.Conventional drugs cannot effectively reach this inflammatory source within the dense cartilage.
文摘Human placenta-derived stem cells (hPDSCs) were isolated by trypsinization and further induced into cartilage cells in vitro.The engineered cartilage was constructed by combining hPDSCs with collagen sponge and the cartilage formation was observed by implantation into nude mice.Results showed that hPDSCs featured mesenchymal stem cells and maintained proliferation in vitro for over 30 passages while remaining undifferentiated.All results indicated that hPDSCs have the potential to differentiate into functional cartilage cells in vitro when combined with collagen sponge,which provided experimental evidence for prospective clinical application.
文摘The limited ability of cartilage tissue to repair itself poses a functionally impairing health problem. While many treatment methods are available, full restoration of the tissue to its original state is rare. Often, complete joint replacement surgery is required to obtain long-term relief. Tissue engineering approaches, however, provide new opportunities for cartilage replacement. They seek to provide mechanisms to repair or replace lost tissue or function. A theoretical method is presented here for regenerating hyaline cartilage in vitro using a chondrocyte-seeded three-dimensional biomimetic engineered scaffold with mechanical properties similar to those occurring naturally. The scaffold composition, type II collagen, aggrecan, hyaluronan, hyaluronan binding protein (for link protein), and BMP-7, were chosen to encourage synthesis of hyaline cartilage by providing a more native environment and signaling cue for the seeded chondrocytes. The scaffold components mimic the macrofibrillar collagen network found in articular cartilage. Type II collagen provides tensile strength, and aggrecan, the predominant proteoglycan, provides compressive strength.
基金National Natural Science Foundation of China(81771047 to J.X.,81670978 and 81870754 to X.Z.)Sichuan Science&Technology Innovation Talent Project(2022JDRC0044)。
文摘Articular cartilage serves as a low-friction,load-bearing tissue without the support with blood vessels,lymphatics and nerves,making its repair a big challenge.Transforming growth factor-beta 3(TGF-β3),a vital member of the highly conserved TGF-βsuperfamily,plays a versatile role in cartilage physiology and pathology.TGF-β3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses,including cell survival,proliferation,migration,and differentiation.Since TGF-β3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy,its regulatory role is especially important to cartilage development.Increased TGF-β3 plays a dual role:in healthy tissues,it can facilitate chondrocyte viability,but in osteoarthritic chondrocytes,it can accelerate the progression of disease.Recently,TGF-β3 has been recognized as a potential therapeutic target for osteoarthritis(OA)owing to its protective effect,which it confers by enhancing the recruitment of autologous mesenchymal stem cells(MSCs)to damaged cartilage.However,the biological mechanism of TGF-β3 action in cartilage development and OA is not well understood.In this review,we systematically summarize recent progress in the research on TGF-β3 in cartilage physiology and pathology,providing up-to-date strategies for cartilage repair and preventive treatment.
基金National Key R&D Program of China(2022YFA1103200,2017YFA0106400,2021YFA1100900)Ministry of Science and Technology of China(2020YFC2002804)+3 种基金National Natural Science Foundation of China(91749124,81772389,82070108)Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004)Fundamental Research Funds for the Central Universities(22120190149 and kx0200020173386)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai。
文摘Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.
基金supported by the National Natural Science Foundation of China(NSFC)No.82071139(to S.Z.),81873720(to B.Y.),82270999(to R.B.)Key R&D Program of Sichuan Provincial Department of Science and Technology No.23ZDYF2130(to S.Z.)+2 种基金Sichuan Science and Technology Program No.2022NSFSC1382(to Y.H.)‘From Zero to One’Innovative Research Program of Sichuan University No.2022SCUH0022(to R.B.)Clinical Research Program of West China Hospital of Stomatology,LCYJ2023-DL-5。
文摘The anterior disc displacement(ADD)leads to temporomandibular joint osteoarthritis(TMJOA)and mandibular growth retardation in adolescents.To investigate the potential functional role of fibrocartilage stem cells(FCSCs)during the process,a surgical ADDTMJOA mouse model was established.From 1 week after model generation,ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis(OA)-like joint cartilage degeneration,manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis.Lineage tracing using Gli1^(-)CreER^(+);Tm^(fl/-)mice and Sox9-CreER^(+);Tm^(fl/-)mice showed that ADD interfered with the chondrogenic capacity of Gli1+FCSCs as well as osteogenic differentiation of Sox9+lineage,mainly in the middle zone of TMJ cartilage.Then,a surgically induced disc reposition(DR)mouse model was generated.The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice.And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment.In conclusion,ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage,resulting in cartilage degeneration and loss of subchondral bone homeostasis,finally causing TMJ growth retardation.DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.
文摘This study is designed to determine whether the outermost layer of articular cartilage is deficient in Osteoarthritis (OA). Phospholipids present in healthy and osteoarthritis (OA) synovial fluid show significant differences in their concentration. While examining the surface properties of OA joints, we found that OA PLs molecules cannot support lubrication, and increased friction was observed. Our lubrication mechanism was based on a surface active phospholipids (SAPL) multibilayer which in OA condition was deactivated and removed from the cartilage surface under OA conditions. Cartilage wettability study clearly demonstrated a significant decrease in hydrophobicity, the contact angle, θ (theta), dropping from 103° from bovine healthy cartilage to 65° in surface partially depleted and 35.1° for completely depleted surface. These results are discussed in the context that surface active phospholipid (SAPL) and lubricin, each has specific roles in a lamellar-repulsive lubrication system. However, deactivated phospholipid molecules are major indicator of cartilage wear (model) introduced in this study.
基金supported by the China Agriculture Research System(CARS-46),China.
文摘Cartilage is a nonedible byproduct with little saleable value.However,previous studies have proposed the possibility of producing peptides from cartilage with immune function modulation potential.The current study aimed to investigate the potential anti-inflammatory activity of peptides derived from sturgeon(Acipenser schrenckii)cartilage in lipopolysaccharide(LPS)-stimulated RAW264.7 macrophages.Five peptide sequences,including four novel peptides,were identified from ethanol-soluble cartilage hydrolysates.Among these five peptides,LTGP,LLLE,LLEL and VGPAGPAGP reduced the production of nitric oxide(NO)and interleukin-6(IL-6)while increasing interleukin-10(IL-10)excretion.Transcriptome analysis suggested the inhibition of activated mitogen-activated protein kinase(MAPK)and interleukin-17(IL-17)signaling pathways after LLEL intervention.MAPK,which is involved in the IL-17 signaling pathway,was further proved to be blocked by downregulating the phosphorylation of p38,extracellular-signal regulated protein kinase(ERK),and c-jun N-terminal kinase(JNK).This novel peptide offers an attractive approach to develop functional foods.
基金the funding provided by the United Kingdom(UK)Engineering and Physical Sciences Research Council(EPSRC)Doctoral Prize Fellowship(EP/R513131/1)。
文摘Articular cartilage damage caused by trauma or degenerative pathologies such as osteoarthritis can result in significant pain,mobility issues,and disability.Current surgical treatments have a limited capacity for efficacious cartilage repair,and long-term patient outcomes are not satisfying.Three-dimensional bioprinting has been used to fabricate biochemical and biophysical environments that aim to recapitulate the native microenvironment and promote tissue regeneration.However,conventional in vitro bioprinting has limitations due to the challenges associated with the fabrication and implantation of bioprinted constructs and their integration with the native cartilage tissue.In situ bioprinting is a novel strategy to directly deliver bioinks to the desired anatomical site and has the potential to overcome major shortcomings associated with conventional bioprinting.In this review,we focus on the new frontier of robotic-assisted in situ bioprinting surgical systems for cartilage regeneration.We outline existing clinical approaches and the utilization of robotic-assisted surgical systems.Handheld and robotic-assisted in situ bioprinting techniques including minimally invasive and non-invasive approaches are defined and presented.Finally,we discuss the challenges and potential future perspectives of in situ bioprinting for cartilage applications.
基金supported by the National Natural Science Foundation of China(No.81171731)the Project of Chengdu Science and Technology Bureau(Nos.2021-YF05-01619-SN and 2021-RC05-00022-CG)+2 种基金the Science and Technology Project of Tibet Autonomous Region(Nos.XZ202202YD0013C and XZ201901-GB-08)the Sichuan Science and Technology Program(No.2022YFG0066)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Nos.ZYJC21026,ZYGD21001 and ZYJC21077).
文摘At present,the clinical reconstruction of the auricle usually adopts the strategy of taking autologous costal cartilage.This method has great trauma to patients,poor plasticity and inaccurate shaping.Three-dimensional(3D)printing technology has made a great breakthrough in the clinical application of orthopedic implants.This study explored the combination of 3D printing and tissue engineering to precisely reconstruct the auricle.First,a polylactic acid(PLA)polymer scaffold with a precisely customized patient appearance was fabricated,and then auricle cartilage fragments were loaded into the 3D-printed porous PLA scaffold to promote auricle reconstruction.In vitro,gelatin methacrylamide(GelMA)hydrogels loaded with different sizes of rabbit ear cartilage fragments were studied to assess the regenerative activity of various autologous cartilage fragments.In vivo,rat ear cartilage fragments were placed in an accurately designed porous PLA polymer ear scaffold to promote auricle reconstruction.The results indicated that the chondrocytes in the cartilage fragments could maintain the morphological phenotype in vitro.After three months of implantation observation,it was conducive to promoting the subsequent regeneration of cartilage in vivo.The autologous cartilage fragments combined with 3D printing technology show promising potential in auricle reconstruction.
文摘Due to the limited self healing capacity of human cartilage,the repair of defects gives rise to a challenging clinical problem.Cartilage tissue engineering provides a new method to solve cartilage repair.However,the search for a suitable biological vector material has long been the focus of research interest in this regard.In this paper,the present situation of cartilage tissue engineering vector materials is reviewed.