Magnetic resonance imaging for non-invasive clinical evaluation of normal and regenerated cartilage

With the development of tissue engineering and regenerative medicine,it is much desired to establish bioimaging techniques to monitor the real-time regeneration efficacy in vivo in a non-invasive way.Herein,we tried magnetic resonance imaging(MRI)to evaluate knee cartilage regeneration after implanting a biomaterial scaffold seeded with chondrocytes,namely,matrix-induced autologous chondrocyte implantation(MACI).After summary of the T2 mapping and the T1-related delayed gadolinium-enhanced MRI imaging of cartilage(dGEMRIC)in vitro and in vivo in the literature,these two MRI techniques were tried clinically.In this study,18 patients were followed up for 1 year.It was found that there was a significant difference between the regeneration site and the neighboring normal site(control),and the difference gradually diminished with regeneration time up to 1 year according to both the quantitative T1 and T2 MRI methods.We further established the correlation between the quantitative evaluation of MRI and the clinical Lysholm scores for the first time.Hence,the MRI technique was confirmed to be a feasible semiquantitative yet non-invasive way to evaluate the in vivo regeneration of knee articular cartilage.

In vitro genotoxicity evaluation and metabolic study of residual glutaraldehyde in animal-derived biomaterials

Glutaraldehyde(GA)is an important additive that is mainly used in animal-derived biomaterials to improve their mechanical and antimicrobial capacities.However,GA chemical toxicity and the metabolic mechanism remain relatively unknown.Therefore,residual GA has always been a major health risk consideration for animal-derived medical devices.In this study,extracts of three biopatches were tested via the GA determination test and mouse lymphoma assay(MLA).The results showed that dissolved GA was a potential mutagen,which could induce significant cytotoxic and mutagenic effects in mouse lymphoma cells.These toxic reactions were relieved by the S9 metabolic activation(MA)system.Furthermore,we confirmed that GA concentration decreased and glutaric acid was generated during the catalytic process.We revealed GA could be oxidized via cytochrome P450 which was the main metabolic factor of S9.We found that even though GA was possibly responsible for positive reactions of animal-derived biomaterials’biocompatibility evaluation,it may not represent the real situation occurring in human bodies,owing to the presence of various detoxification mechanisms including the S9 system.Overall,in order to achieve a general balance between risk management and practical application,rational decisions based on comprehensive analyses must be considered.

Quantitatively relating magnetic resonance T_(1)and T_(2)to glycosaminoglycan and collagen concentrations mediated by penetrated contrast agents and biomacromolecule-bound water

Magnetic resonance imaging(MRI)is a promising non-invasive method to assess cartilage regeneration based on the quantitative relationship between MRI features and concentrations of the major components in the extracellular matrix(ECM).To this end,in vitro experiments are performed to investigate the relationship and reveal the underlying mechanism.A series of collagen(COL)and glycosaminoglycan(GAG)solutions at different concentrations are prepared,and T_(1)and T_(2)relaxation times are measured with or without a contrast agent(Gd-DTPA2−)by MRI.Fourier transform infrared spectrometry is also used to measure the contents of biomacromolecule-bound water and other water,allowing theoretical derivation of the relationship between biomacromolecules and the resulting T_(2)values.It has been revealed that the MRI signal in the biomacromolecule aqueous systems is mainly influenced by the protons in hydrogens of biomacromolecule-bound water,which we divide into inner-bound water and outer-bound water.We have also found that COL results in higher sensitivity of bound water than GAG in T_(2)mapping.Owing to the charge effect,GAG regulates the penetration of the contrast agent during dialysis and has a more significant effect on T_(1)values than COL.Considering that COL and GAG are the most abundant biomacromolecules in the cartilage,this study is particularly useful for the real-time MRI-guided assessment of cartilage regeneration.A clinical case is reported as an in vivo demonstration,which is consistent with our in vitro results.The established quantitative relation plays a critical academic role in establishing an international standard ISO/TS24560-1:2022‘Clinical evaluation of regenerative knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage(dGEMRIC)and T_(2)mapping’drafted by us and approved by International Standard Organization.

Tissue toxicity following the vaginal administration of nanosilver particles in rabbits

Nanosilver particles are used in various clinical settings because of their antibacterial properties.However,their safety evaluation when used for gynaecological disorders has not been established.Nanosilver particles were administrated in the vagina of New Zealand rabbits,and the pathological appearance of the surrounding tissue was examined by hematoxylin–eosin staining and transmission electron microscopy(TEM)after 1 and 3 days of treatment.The nanosilver content was assessed by plasma mass spectrometry,and the presence of particles in the hepatic portal vein blood was assessed by TEM.The results of our study show that the vaginal administration of nanosilver particles caused ultrastructural changes to the vaginal mucosa,urethra and rectum,with accumulation of particles in all tissues.These results demonstrate a new migration route of nanosilver particles following vaginal administration.They also demonstrate,for the first time,that the vaginal administration of nanosilver particles can enter the blood circulation system by examining the hepatic portal vein blood under the TEM which is the most direct visualized evidence.