Meniscus heterogeneity and 3D-printed strategies for engineering anisotropic meniscus.

The meniscus is a fibrocartilaginous tissue of the knee joint that plays an important role in load transmission, shock absorption, joint stability maintenance, and contact stress reduction. Mild meniscal injuries can be treated with simple sutures, whereas severe injuries inevitably require meniscectomy. Meniscectomy destroys the mechanical microenvironment of the knee joint, leading to cartilage degeneration and osteoarthritis. Tissue engineering techniques, as a strategy with diverse sources and customizable and adjustable mechanical and biological properties, have emerged as promising approaches for the treatment of meniscal injuries and are represented by 3D printing. Notably, the heterogeneity of the meniscus, including its anatomical structure, cell phenotype, extracellular matrix, and biomechanical properties, is crucial for its normal function. Therefore, the construction of heterogeneous tissue-engineered menisci (TEM) has become a research hotspot in this field. In this review, we systematically summarize the heterogeneity of menisci and 3D-printed strategies for tissue-engineered anisotropic menisci. The manufacturing techniques, biomaterial combinations, surface functionalization, growth factors, and bioreactors related to 3D-printed strategies are introduced and a promising direction for the future research is proposed.

Comparison of the Clinical Outcomes of Revision and Primary ACL Reconstruction: A Matched-Pair Analysis With 3-5 Years of Follow-up.

BACKGROUND: There are limited studies designed by matching related factors to compare clinical outcomes and return to sport (RTS) between patients undergoing revision anterior cruciate ligament reconstruction (R-ACLR) and primary ACLR (P-ACLR). PURPOSE: (1) To compare the outcomes between R-ACLR and P-ACLR in a matched-pair analysis with 3- to 5-year follow-up and (2) to evaluate patient-reported factors for not returning to preinjury-level sport. STUDY DESIGN: Cohort study; Level of evidence, 4. METHODS: Patients who underwent R-ACLR between September 2016 and November 2018 were propensity matched by age, sex, body mass index, passive anterior tibial subluxation, and generalized hypermobility in a 1:1 ratio to patients who underwent P-ACLR during the same period. By combining in person follow-up at 2 years postoperatively and telemedicine interview at the final follow-up (January 2022), knee stability and clinical scores were compared, including International Knee Documentation Committee (IKDC), Lysholm, and Tegner. Status of RTS was requested, specifically whether the patient returned to preinjury level of sport. Patient-reported reasons for not returning were analyzed. RESULTS: There were 63 matched pairs in the present study. Knee stability was similar in terms of KT-2000 arthrometer, Lachman test, and pivot-shift test results between the groups at 2 years of follow-up. At the final follow-up, no significant difference was found between groups for postoperative clinical scores (IKDC, Tegner, and Lysholm) (P > .05). There was a significant difference in total RTS: 53 (84.1%) in the P-ACLR cohort and 41 (65.1%) in the R-ACLR cohort (P = .014). No significant difference was shown in terms of RTS at the same level: 35 (55.6%) in P-ACLR and 31 (49.2%) in R-ACLR (P = .476). Significantly more patients showed fear of reinjury: 26 of 32 (81.3%) in the R-ACLR group as compared with 15 of 28 (53.5%) in the P-ACLR group (P < .021). CONCLUSION: R-ACLR resulted in similar clinical scores (IKDC, Tegner, and Lysholm) but significantly lower RTS versus P-ACLR at 3 to 5 years of follow-up. Fear of reinjury was the most common factor that caused sport changes in patients with R-ACLR.

An immunomodulatory polypeptide hydrogel for osteochondral defect repair.

Osteochondral injury is a common and frequent orthopedic disease that can lead to more serious degenerative joint disease. Tissue engineering is a promising modality for osteochondral repair, but the implanted scaffolds are often immunogenic and can induce unwanted foreign body reaction (FBR). Here, we prepare a polypept(o)ide-based PAA-RGD hydrogel using a novel thiol/thioester dual-functionalized hyperbranched polypeptide P(EG3Glu-co-Cys) and maleimide-functionalized polysarcosine under biologically benign conditions. The PAA-RGD hydrogel shows suitable biodegradability, excellent biocompatibility, and low immunogenicity, which together lead to optimal performance for osteochondral repair in New Zealand white rabbits even at the early stage of implantation. Further in vitro and in vivo mechanistic studies corroborate the immunomodulatory role of the PAA-RGD hydrogel, which induces minimum FBR responses and a high level of polarization of macrophages into the immunosuppressive M2 subtypes. These findings demonstrate the promising potential of the PAA-RGD hydrogel for osteochondral regeneration and highlight the importance of immunomodulation. The results may inspire the development of PAA-based materials for not only osteochondral defect repair but also various other tissue engineering and bio-implantation applications.

Immunomodulatory PEG-CRGD Hydrogels Promote Chondrogenic Differentiation of PBMSCs.

Cartilage damage is a common injury. Currently, tissue engineering scaffolds with composite seed cells have emerged as a promising approach for cartilage repair. Polyethylene glycol (PEG) hydrogels are attractive tissue engineering scaffold materials as they have high water absorption capacity as well as nontoxic and nutrient transport properties. However, PEG is fundamentally bio-inert and lacks intrinsic cell adhesion capability, which is critical for the maintenance of cell function. Cell adhesion peptides are usually added to improve the cell adhesion capability of PEG-based hydrogels. The suitable cell adhesion peptide can not only improve cell adhesion capability, but also promote chondrogenesis and regulate the immune microenvironment. To improve the interactions between cells and PEG hydrogels, we designed cysteine-arginine-glycine-aspartic acid (CRGD), a cell adhesion peptide covalently cross-linked with PEG hydrogels by a Michael addition reaction, and explored the tissue-engineering hydrogels with immunomodulatory effects and promoted chondrogenic differentiation of mesenchymal stem cells (MSCs). The results indicated that CRGD improved the interaction between peripheral blood mesenchymal stem cells (PBMSCs) and PEG hydrogels. PEG hydrogels modified with 1 mM CRGD had the optimal capacity to promote chondrogenic differentiation, and CRGD could induce macrophage polarization towards the M2 phenotype to promote tissue regeneration and repair. PEG-CRGD hydrogels combined with PBMSCs have the potential to be suitable scaffolds for cartilage tissue engineering.

Kartogenin-Conjugated Double-Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair.

The effectiveness of existing tissue-engineering cartilage (TEC) is known to be hampered by weak integration of biocompatibility, biodegradation, mechanical strength, and microenvironment supplies. The strategy of hydrogel-based TEC holds considerable promise in circumventing these problems. Herein, a non-toxic, biodegradable, and mechanically optimized double-network (DN) hydrogel consisting of polyethylene glycol (PEG) and kartogenin (KGN)-conjugated chitosan (CHI) is constructed using a simple soaking strategy. This PEG-CHI-KGN DN hydrogel possesses favorable architectures, suitable mechanics, remarkable cellular affinity, and sustained KGN release, which can facilitate the cartilage-specific genes expression and extracellular matrix secretion of peripheral blood-derived mesenchymal stem cells (PB-MSCs). Notably, after tracing the transplanted cells by detecting the rabbit sex-determining region Y-linked gene sequence, the allogeneic PB-MSCs are found to survive for even 3 months in the regenerated cartilage. Here, the long-term release of KGN is able to efficiently and persistently activate multiple genes and signaling pathways to promote the chondrogenesis, chondrocyte differentiation, and survival of PB-MSCs. Thus, the regenerated tissues exhibit well-matched histomorphology and biomechanical performance such as native cartilage. Consequently, it is believed this innovative work can expand the choice for developing the next generation of orthopedic implants in the loadbearing region of a living body.

A Tumor Accelerator Based on Multicomponent Bone Scaffolds and Cancer Cell Homing.

Bone tissue attracts cancer cell homing biologically, mechanically, or chemically. It is difficult and time consuming to identify their complex cross-talk using existed methods. In this study, a multi-component bone matrix was fabricated using gelatin, hydroxyapatite (HAp), and epidermal growth factor (EGF) as raw materials to investigate how "acellular" bone matrix affects cancer cell homing in bone. Then, EGF-responsive cancer cells were cultured with the scaffold in a dynamical bioreactor. For different culture periods, the effects of HAp, gelatin, and EGF on the cell adhesion, proliferation, 3D growth, and migration of cancer were evaluated. The results indicated that a small amount of calcium ion released from the scaffolds accelerated cancer MDA-MB-231 adhesion on the surface of inner pores. Moreover, degradable gelatin key caused cancer cell growth on the scaffold surface to turn into a 3D aggregation. Despite this, the formation of cancer spheroids was slow, and required 14 days of dynamic culture. Thankfully, EGF promoted cancer cell adhesion, proliferation, and migration, and cancer spheroids were observed only after 3-day culture. We concluded that the combination of the multiple components in this scaffold allows cancer cells to meet multiple requirements of cancer dynamic progression.

Integrated Analysis of lncRNA and mRNA Expression Profiles Indicates Age-Related Changes in Meniscus.

Little has been known about the role of long non-coding RNA (lncRNA) involves in change of aged meniscus. Microarray analyses were performed to identify lncRNAs and mRNAs expression profiles of meniscus in young and aging adults and apple bioinformatics methods to analyse their potential roles. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by qRT-PCR. A total of 1608 DE lncRNAs and 1809 DE mRNAs were identified. Functional and pathway enrichment analyses of all DE mRNAs showed that DE mRNAs were mainly involved in the TGF-beta, Wnt, Hippo, PI3K-Akt signaling pathway. The expressions of TNFRSF11B and BMP2 were significantly upregulated in aging group. LASSO logistic regression analysis of the DE lncRNAs revealed four lncRNAs (AC124312.5, HCG11, POC1B-AS1, and AP001011.1) that were associated with meniscus degradation. CNC analysis demonstrated that AP001011 inhibited the expression of TNFRSF11B and AC1243125 upregulated the expression of TNFRSF11B. CeRNA analysis suggested that POC1B-AS1 regulates the expression of BMP2 by sponging miR 130a-3p, miR136-5p, miR 18a-3p, and miR 608. Furthermore, subcellular localization and m6A modification sites prediction analysis of these four lncRNAs was performed. These data lay a foundation for extensive studies on the role of lncRNAs in change of aged meniscus.

Physical therapy and orthopaedic equipment-induced reduction in the biomechanical risk factors related to knee osteoarthritis: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

OBJECTIVE: Are physical therapy or orthopaedic equipment efficacious in reducing the biomechanical risk factors in people with tibiofemoral osteoarthritis (OA)? Is there a better therapeutic intervention than others to improve these outcomes? DESIGN: Systematic review with network meta-analysis (NMA) of randomised trials. DATA SOURCES: PubMed, Web of Science, Cochrane Library, Embase and MEDLINE were searched through January 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomised controlled trials exploring the benefits of using physical therapy or orthopaedic equipment in reducing the biomechanical risk factors which included knee adduction moment (KAM) and knee adduction angular impulse (KAAI) in individuals with tibiofemoral OA. DATA EXTRACTION AND SYNTHESIS: Two authors extracted data independently and assessed risk of bias. We conducted an NMA to compare multiple interventions, including both direct and indirect evidences. Heterogeneity was assessed (sensitivity analysis) and quantified (I2 statistic). Grading of Recommendations Assessment, Development and Evaluation assessed the certainty of the evidence. RESULTS: Eighteen randomised controlled trials, including 944 participants, met the inclusion criteria, of which 14 trials could be included in the NMA. Based on the collective probability of being the overall best therapy for reducing the first peak KAM, lateral wedge insoles (LWI) plus knee brace was closely followed by gait retraining, and knee brace only. Although no significant difference was observed among the eight interventions, variable-stiffness shoes and neuromuscular exercise exhibited an increase in the first peak KAM compared with the control condition group. And based on the collective probability of being the overall best therapy for reducing KAAI, gait retraining was followed by LWI only, and lower limb exercise. CONCLUSION: The results of our study support the use of LWI plus knee brace for reducing the first peak KAM. Gait retraining did not rank highest but it influenced both KAM and KAAI and therefore it was the most recommended therapy for reducing the biomechanical risk factors.

Association between cyclic variation in the heart rate index and biomarkers of neurodegenerative diseases in obstructive sleep apnea syndrome: A pilot study.

PURPOSE: Obstructive sleep apnea syndrome (OSAS) has mostly been examined using in-laboratory polysomnography (Lab-PSG), which may overestimate severity. This study compared sleep parameters in different environments and investigated the association between the plasma levels of neurochemical biomarkers and sleep parameters. METHODS: Thirty Taiwanese participants underwent Lab-PSG while wearing a single-lead electrocardiogram patch. Participants' blood samples were obtained in the morning immediately after the recording. Participants wore the patch for the subsequent three nights at home. Sleep disorder indices were calculated, including the apnea-hypopnea index (AHI), chest effort index, and cyclic variation of heart rate index (CVHRI). The 23 eligible participants' derived data were divided into the normal-to-moderate (N-M) group and the severe group according to American Association of Sleep Medicine (AASM) guidelines (Lab-PSG) and the recommendations of a previous study (Rooti Rx). Spearman's correlation was used to examine the correlations between sleep parameters and neurochemical biomarker levels. RESULTS: The mean T-Tau protein level was positively correlated with the home-based CVHRI (r = 0.53, p < 0.05), whereas no significant correlation was noted between hospital-based CVHRI and the mean T-tau protein level (r = 0.25, p = 0.25). The home-based data revealed that the mean T-Tau protein level in the severe group was significantly higher than that in the N-M group (severe group: 24.75 ± 6.16 pg/mL, N-M group: 19.65 ± 3.90 pg/mL; p < 0.05). Furthermore, the mean in-hospital CVHRI was higher than the mean at-home values (12.16 ± 13.66 events/h). CONCLUSION: Severe OSAS patients classified by home-based CVHRI demonstrated the higher T-Tau protein level, and CVHRI varied in different sleep environments.

Machine learning approaches for screening the risk of obstructive sleep apnea in the Taiwan population based on body profile.

(a) Objective: Obstructive sleep apnea syndrome (OSAS) is typically diagnosed through polysomnography (PSG). However, PSG incurs high medical costs. This study developed new models for screening the risk of moderate-to-severe OSAS (apnea-hypopnea index, AHI ≥15) and severe OSAS (AHI ≥30) in various age groups and sexes by using anthropometric features in the Taiwan population.(b) Participants: Data were derived from 10,391 northern Taiwan patients who underwent PSG.(c) Methods: Patients' characteristics - namely age, sex, body mass index (BMI), neck circumference, and waist circumference - was obtained. To develop an age- and sex-independent model, various approaches - namely logistic regression, k-nearest neighbor, naive Bayes, random forest (RF), and support vector machine - were trained for four groups based on sex and age (men or women; aged <50 or ≥50 years). Dataset was separated independently (training:70%; validation: 10%; testing: 20%) and Cross-validated grid search was applied for model optimization. Models demonstrating the highest overall accuracy in validation outcomes for the four groups were used to predict the testing dataset.(d) Results: The RF models showed the highest overall accuracy. BMI was the most influential parameter in both types of OSAS severity screening models.(e) Conclusion: The established models can be applied to screen OSAS risk in the Taiwan population and those with similar craniofacial features.

Fabrication of Injectable Chitosan-Chondroitin Sulfate Hydrogel Embedding Kartogenin-Loaded Microspheres as an Ultrasound-Triggered Drug Delivery System for Cartilage Tissue Engineering.

Ultrasound-responsive microspheres (MPs) derived from natural polysaccharides and injectable hydrogels have been widely investigated as a biocompatible, biodegradable, and controllable drug delivery system and cell scaffolds for tissue engineering. In this study, kartogenin (KGN) loaded poly (lactide-co-glycolic acid) (PLGA) MPs (MPs@KGN) were fabricated by premix membrane emulsification (PME) method which were sonicated by an ultrasound transducer. Furthermore, carboxymethyl chitosan-oxidized chondroitin sulfate (CMC-OCS) hydrogel were prepared via the Schiff' base reaction-embedded MPs to produce a CMC-OCS/MPs scaffold. In the current work, morphology, mechanical property, porosity determination, swelling property, in vitro degradation, KGN release from scaffolds, cytotoxicity, and cell bioactivity were investigated. The results showed that MPs presented an obvious collapse after ultrasound treatment. The embedded PLGA MPs could enhance the compressive elastic modulus of soft CMC-OCS hydrogel. The cumulative release KGN from MPs exhibited a slow rate which would display an appropriate collapse after ultrasound, allowing KGN to maintain a continuous concentration for at least 28 days. Moreover, the composite CMC-OCS@MPs scaffolds exhibited faster gelation, lower swelling ratio, and lower in vitro degradation. CCK-8 and LIVE/DEAD staining showed these scaffolds did not influence rabbit bone marrow mesenchymal stem cells (rBMMSCs) proliferation. Then these scaffolds were cultured with rBMMSCs for 2 weeks, and the immunofluorescent staining of collagen II (COL-2) showed that CMC-OCS hydrogel embedded with MPs@KGN (CMC-OCS@MPs@KGN) with ultrasound had the ability to increase the COL-2 synthesis. Overall, due to the improved mechanical property and the ability of sustained KGN release, this injectable hydrogel with ultrasound-responsive property is a promising system for cartilage tissue engineering.

Principles for establishment of the stem cell bank and its applications on management of sports injuries.

BACKGROUND: The stem cells of the stem cell banks have prominent problems for insufficient sources, easy contamination, unstable biological characteristics after serial subcultivations, and high cost. METHODS: After collecting the construction processes of the existing stem cell banks and suggestions from authoritative experts in the past 10 years, 230 reference principles were obtained, and finally, the principles of "5C" for the establishment of modern standardized stem cell banks were summarized, and their related applications on the management of sports injuries were reviewed as well. RESULTS: The basic principles of "5C" for the establishment of modern standardized stem cell banks include (1) principle of informed consent, (2) confidentiality principle, (3) conformity principle, (4) contamination-free principle, and (5) commonweal principle. The applications of stem cells on repairs, reconstructions, and regenerations of sports injuries were also reviewed, especially in tissue-engineered cartilage, tissue-engineered meniscus, and tissue-engineered ligament. CONCLUSIONS: The proposal of the basic principles of "5C" is conducive to relevant stem cell researchers and clinical medical experts to build modern stem cell banks in a more standardized and efficient manner while avoiding some major mistakes or problems that may occur in the future. On this basis, stem cells from stem cell banks would be increasingly used in the management of sports injuries. More importantly, these days, getting stem cell samples are difficult in a short time, and such banks with proper legal consent may help the scientific community.

MicroRNA-210-3p Promotes Chondrogenic Differentiation and Inhibits Adipogenic Differentiation Correlated with HIF-3α Signalling in Bone Marrow Mesenchymal Stem Cells.

Cartilage injury of the knee joint is very common. Due to the limited self-healing ability of articular cartilage, osteoarthritis is very likely to occur if left untreated. Bone marrow mesenchymal stem cells (BMMSCs) are widely used in the study of cartilage injury due to their low immunity and good amplification ability, but they still have disadvantages, such as heterogeneous undifferentiated cells. MicroRNAs can regulate the chondrogenic differentiation ability of MSCs by inhibiting or promoting mRNA translation and degradation. In this research, we primarily investigated the effect of microRNA-210-3p (miR-210-3p) on chondrogenic and adipogenic differentiation of BMMSCs in vitro. Our results demonstrate that miR-210-3p promoted chondrogenic differentiation and inhibited adipogenic differentiation of rat BMMSCs, which was related to the HIF-3α signalling pathway. Additionally, miR-210-3p promotes mRNA and protein levels of the chondrogenic expression genes COLII and SOX9 and inhibits mRNA and protein levels of the adipogenic expression genes PPARγ and LPL. Thus, miR-210-3p combined with BMMSCs is a candidate for future clinical applications in cartilage regeneration and could represent a promising new therapeutic target for OA.

Tibial Tubercle Osteotomy May Not Provide Additional Benefit in Treating Patellar Dislocation With Increased Tibial Tuberosity-Trochlear Groove Distance: A Systematic Review.

PURPOSE: To examine the indications and outcomes of medial patellofemoral ligament reconstruction (MPFLR) with or without tibial tubercle osteotomy (TTO) in treating recurrent or habitual patellar dislocation with an increased tibial tuberosity-trochlear groove (TT-TG) distance. METHODS: We performed a literature search of the established medical databases Cochrane Central, PubMed-MEDLINE, EMBASE, and Web of Science. The inclusion criteria were as follows: skeletally mature patients with recurrent or habitual patellar dislocation and an increased TT-TG distance, treatment with MPFLR combined with a TTO procedure or isolated MPFLR, and reporting of clinical outcomes and complications. Each study was assessed for quality and the level of evidence. The general characteristics, indications, surgical techniques, TT-TG distance, clinical results, imaging evaluation findings, and complications of each study were recorded. RESULTS: Nine studies consisting of 288 knees met the inclusion criteria. The average Coleman score was 71.56 (range, 55-83). The threshold for an increased TT-TG distance ranged from 16 to 20 mm in the included studies. Similar good postoperative outcomes were reported in patients with an increased TT-TG distance treated with MPFLR with versus without a TTO procedure. The mean postoperative Lysholm score ranged from 75.0 to 94.7 (I2 = 87.6%) in the isolated MPFLR group and from 85.0 to 87.6 (I2 = 16.3%) in the TTO-with-MPFLR group. Similar postoperative congruence angles were reported in both groups. The postoperative redislocation rate ranged from 0% to 4.2% in the TTO-with-MPFLR group, and no redislocation was found in the isolated MPFLR group. The postoperative apprehension sign was only reported in isolated MPFLR patients. CONCLUSIONS: The outcomes of MPFLR with or without TTO to treat recurrent or habitual patellar dislocation with an increased TT-TG distance appeared similar. However, this study was limited by the considerable heterogeneity, variety of techniques, variety of TT-TG distances, and variability in patella alta and trochlear dysplasia among the included studies. LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

Scaffold-Based Tissue Engineering Strategies for Osteochondral Repair.

Over centuries, several advances have been made in osteochondral (OC) tissue engineering to regenerate more biomimetic tissue. As an essential component of tissue engineering, scaffolds provide structural and functional support for cell growth and differentiation. Numerous scaffold types, such as porous, hydrogel, fibrous, microsphere, metal, composite and decellularized matrix, have been reported and evaluated for OC tissue regeneration in vitro and in vivo, with respective advantages and disadvantages. Unfortunately, due to the inherent complexity of organizational structure and the objective limitations of manufacturing technologies and biomaterials, we have not yet achieved stable and satisfactory effects of OC defects repair. In this review, we summarize the complicated gradients of natural OC tissue and then discuss various osteochondral tissue engineering strategies, focusing on scaffold design with abundant cell resources, material types, fabrication techniques and functional properties.

Function and Mechanism of RGD in Bone and Cartilage Tissue Engineering.

Bone and cartilage injury is common, tissue engineered scaffolds are potential means to repair. Because most of the scaffold materials used in bone and cartilage tissue engineering are bio-inert, it is necessary to increase the cellular adhesion ability of during tissue engineering reconstruction. The Arginine - Glycine - Aspartic acid (Arg-Gly-Asp, RGD) peptide family is considered as a specific recognition site for the integrin receptors. Integrin receptors are key regulators of cell-cell and cell-extracellular microenvironment communication. Therefore, the RGD polypeptide families are considered as suitable candidates for treatment of a variety of diseases and for the regeneration of various tissues and organs. Many scaffold material for tissue engineering and has been approved by US Food and Drug Administration (FDA) for human using. The application of RGD peptides in bone and cartilage tissue engineering was reported seldom. Only a few reviews have summarized the applications of RGD peptide with alloy, bone cements, and PCL in bone tissue engineering. Herein, we summarize the application progress of RGD in bone and cartilage tissue engineering, discuss the effects of structure, sequence, concentration, mechanical stimulation, physicochemical stimulation, and time stimulation of RGD peptide on cells differentiation, and introduce the mechanism of RGD peptide through integrin in the field of bone and cartilage tissue engineering.

Advances in the Application of Supramolecular Hydrogels for Stem Cell Delivery and Cartilage Tissue Engineering.

Cartilage defects pose a great threat to the health of the aging population. Cartilage has limited self-regeneration ability because it lacks blood vessels, nerves and lymph. To achieve efficient cartilage regeneration, supramolecular hydrogels are used in medical applications and tissue engineering as they are tunable and reversible in nature. Moreover, they possess supramolecular interactions which allow the incorporation of cells. These hydrogels present great potential for tissue engineering-based therapies. This review presents advances in the development of stem cell-laden supramolecular hydrogels. We discuss new possibilities for stem cell therapy and their uses in cartilage tissue engineering. Gray areas and future perspectives are discussed.

Facile Strategy on Hydrophilic Modification of Poly(ε-caprolactone) Scaffolds for Assisting Tissue-Engineered Meniscus Constructs In Vitro.

Poly(ε-caprolactone) (PCL) derived scaffolds have been extensively explored in the field of tissue-engineered meniscus (TEM) originating from their good biosafety and biomechanical properties. However, the poor intrinsic hydrophobicity severely hindered their wide applications for the scaffold-assisted tissue regeneration. Herein, we developed a simple strategy on surface modification of three-dimensional (3D) PCL scaffolds via a simply soaking treatment of sodium hydroxide (NaOH) solutions to increase the hydrophilicity and roughness of scaffolds' surfaces. We investigated the effect of hydrolysis degree mediated by NaOH solutions on mechanical properties of 3D scaffolds, considering the importance of scaffolds' resistance to internal force. We also investigated and analyzed the biological performances of mesenchymal stromal cells (MSCs) and meniscal fibrocartilage cells (MFCs) onto the scaffolds treated or untreated by NaOH solutions. The results indicated that hydrophilic modification could improve the proliferation and attachment of cells on the scaffolds. After careful screening process condition, structural fabrication, and performance optimization, these modified PCL scaffolds possessed roughened surfaces with inherent hierarchical pores, enhanced hydrophilicity and preferable biological performances, thus exhibiting the favorable advantages on the proliferation and adhesion of seeded cells for TEM. Therefore, this feasible hydrophilic modification method is not only beneficial to promote smarter biomedical scaffold materials but also show great application prospect in tissue engineering meniscus with tunable architectures and desired functionalities.

Advances of Stem Cell-Laden Hydrogels With Biomimetic Microenvironment for Osteochondral Repair.

Osteochondral damage from trauma or osteoarthritis is a general joint disease that can lead to an increased social and economic burden in the modern society. The inefficiency of osteochondral defects is mainly due to the absence of suitable tissue-engineered substrates promoting tissue regeneration and replacing damaged areas. The hydrogels are becoming a promising kind of biomaterials for tissue regeneration. The biomimetic hydrogel microenvironment can be tightly controlled by modulating a number of biophysical and biochemical properties, including matrix mechanics, degradation, microstructure, cell adhesion, and intercellular interactions. In particular, advances in stem cell-laden hydrogels have offered new ideas for the cell therapy and osteochondral repair. Herein, the aim of this review is to underpin the importance of stem cell-laden hydrogels on promoting the development of osteochondral regeneration, especially in the field of manipulation of biomimetic microenvironment and utilization growth factors with various delivery methods.

The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review.

BACKGROUND: Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and in vivo safety remain unclear. METHODS: PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage in vivo were selected for analysis. RESULTS: A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair in vivo without serious adverse events. CONCLUSION: Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration in vivo are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans.