Injection and Self‐Assembly of Bioinspired Stem Cell‐Laden Gelatin/Hyaluronic Acid Hybrid Microgels Promote Cartilage Repair In Vivo

2019 ◽  
Vol 29 (50) ◽  
pp. 1906690 ◽  
Author(s):  
Qi Feng ◽  
Qingtao Li ◽  
Hongji Wen ◽  
Jingxuan Chen ◽  
Minhua Liang ◽  
...  
Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 432
Author(s):  
Chin-Chean Wong ◽  
Shi-Da Sheu ◽  
Pei-Chun Chung ◽  
Yi-Yen Yeh ◽  
Chih-Hwa Chen ◽  
...  

The main aim of this study is to investigate the therapeutic efficacy of direct intra-articular injection of bone-marrow-derived stem/stromal cells (BMSCs) and the adjuvant role of hyaluronic acid (HA) in facilitating rabbit articular cartilage repair. First, rabbit BMSCs were treated with a medium containing different concentrations of HA. Later, HA’s influence on BMSCs’ CD44 expression, cell viability, extracellular glycosaminoglycan (GAG) synthesis, and chondrogenic gene expression was evaluated during seven-day cultivation. For the in vivo experiment, 24 rabbits were used for animal experiments and 6 rabbits were randomly allocated to each group. Briefly, chondral defects were created at the medial femoral condyle; group 1 was left untreated, group 2 was injected with HA, group 3 was transplanted with 3 × 106 BMSCs, and group 4 was transplanted with 3 × 106 BMSCs suspended in HA. Twelve weeks post-treatment, the repair outcome in each group was assessed and compared both macroscopically and microscopically. Results showed that HA treatment can promote cellular CD44 expression. However, the proliferation rate of BMSCs was downregulated when treated with 1 mg/mL (3.26 ± 0.03, p = 0.0002) and 2 mg/mL (2.61 ± 0.04, p =0.0001) of HA compared to the control group (3.49 ± 0.05). In contrast, 2 mg/mL (2.86 ± 0.3) of HA treatment successfully promoted normalized GAG expression compared to the control group (1.88 ± 0.06) (p = 0.0009). The type II collagen gene expression of cultured BMSCs was significantly higher in BMSCs treated with 2 mg/mL of HA (p = 0.0077). In the in vivo experiment, chondral defects treated with combined BMSC and HA injection demonstrated better healing outcomes than BMSC or HA treatment alone in terms of gross grading and histological scores. In conclusion, this study helps delineate the role of HA as a chondrogenic adjuvant in augmenting the effectiveness of stem-cell-based injection therapy for in vivo cartilage repair. From a translational perspective, the combination of HA and BMSCs is a convenient, ready-to-use, and effective formulation that can improve the therapeutic efficacy of stem-cell-based therapies.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.


2021 ◽  
Vol 17 (5) ◽  
pp. 901-909
Author(s):  
Long Han ◽  
Nanwei Xu ◽  
Songwei Lv ◽  
Jianjian Yin ◽  
Dong Zheng ◽  
...  

Alginate/Silk fibroin/hyaluronic acid (ALG/SF/HA) nanocomposites were synthesised using blending, inter-linking, and lyophilization methods. We investigated the physicochemical properties of the resulting nanocomposites, including their water retention, weight loss, porosity and cytocompatibility. The optimum ratios of the ALG/SF/HA scaffolding were 3:6.5:0.5. Nanocomposites with optimum ratios were then prepared by integrating pilose antler polypeptides (PAPS) to poly(lactic-co-glycolic acid) (PLGA) microspheres, and the performance was investigated. PAPS-ALG/SF/HA nanocomposites exhibited desirable adhesions and proliferations. Rabbit cartilage deficiencies was developed by the animal model. The cartilage repair effects deficiencies were detected and analyzed between PAPS-SF/ALG/ALG/SF/HA, and control activity classes. The deficiencies were virtually fully remedied after 13 weeks in the presence of PAPS-ALG/SF/HA class, suggesting that the PAPS-ALG/SF/HA nanocomposites had a positive effects on joint cartilage repair.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 593
Author(s):  
Kyungmin Lee ◽  
Gwangjun Go ◽  
Ami Yoo ◽  
Byungjeon Kang ◽  
Eunpyo Choi ◽  
...  

Recently, significant research efforts have been devoted toward the development of magnetically controllable drug delivery systems, however, drug fixation after targeting remains a challenge hindering long-term therapeutic efficacy. To overcome this issue, we present a wearable therapeutic fixation device for fixing magnetically controllable therapeutic agent carriers (MCTACs) at defect sites and its application to cartilage repair using stem cell therapeutics. The developed device comprises an array of permanent magnets based on the Halbach array principle and a wearable band capable of wrapping the target body. The design of the permanent magnet array, in terms of the number of magnets and array configuration, was determined through univariate search optimization and 3D simulation. The device was fabricated for a given rat model and yielded a strong magnetic flux density (exceeding 40 mT) in the region of interest that was capable of fixing the MCTAC at the desired defect site. Through in-vitro and in-vivo experiments, we successfully demonstrated that MCTACs, both a stem cell spheroid and a micro-scaffold for cartilage repair, could be immobilized at defect sites. This research is expected to advance precise drug delivery technology based on MCTACs, enabling subject-specific routine life therapeutics. Further studies involving the proposed wearable fixation device will be conducted considering prognostics under actual clinical settings.


2019 ◽  
Vol 7 (36) ◽  
pp. 5490-5501 ◽  
Author(s):  
Penggang Ren ◽  
Hua Zhang ◽  
Zhong Dai ◽  
Fang Ren ◽  
Yidong Wu ◽  
...  

Pluronic F127 diacrylate (F127DA) micelle-crosslinked methacrylated hyaluronic acid (MeHA) hydrogel with low-swelling and strong compressive properties was successfully synthesized for the regeneration of cartilages in vivo.


RSC Advances ◽  
2016 ◽  
Vol 6 (84) ◽  
pp. 80851-80866 ◽  
Author(s):  
A. Aravamudhan ◽  
D. M. Ramos ◽  
N. A. Jenkins ◽  
N. A. Dyment ◽  
M. M. Sanders ◽  
...  

This manuscript reports the characterization of molecularly self-assembled collagen nanofibers on a natural polymeric microporous structure and their ability to support stem cell differentiation in vitro and host tissue response in vivo.


Author(s):  
Wassif Kabir ◽  
Claudia Di Bella ◽  
Imkyeong Jo ◽  
Daniel Gould ◽  
Peter F.M. Choong

Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.


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