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Articular cartilage regeneration is one of the challenges faced by orthopedic surgeons. Microcarrier applications have made great advances in cartilage tissue engineering in recent years and enable cost-effective cell expansion, thus providing permissive microenvironments for cells. In addition, microcarriers can be loaded with proteins, factors, and drugs for cartilage regeneration. Some microcarriers also have the advantages of injectability and targeted delivery. The application of microcarriers with these characteristics can overcome the limitations of traditional methods and provide additional advantages. In terms of the transformation potential, microcarriers have not only many advantages, such as providing sufficient and beneficial cells, factors, drugs, and microenvironments for cartilage regeneration, but also many application characteristics; for example, they can be injected to reduce invasiveness, transplanted after microtissue formation to increase efficiency, or combined with other stents to improve mechanical properties. Therefore, this technology has enormous potential for clinical transformation. In this review, we focus on recent advances in microcarriers for cartilage regeneration. We compare the characteristics of microcarriers with other methods for repairing cartilage defects, provide an overview of the advantages of microcarriers, discuss the potential of microcarrier systems, and present an outlook for future development. Translational potential of this article We reviewed the advantages and recent advances of microcarriers for cartilage regeneration. This review could give many scholars a better understanding of microcarriers, which can provide doctors with potential methods for treating patients with cartilage injure.

Objective The aim of the present paper was to evaluate the results of one‐stage total hip arthroplasty (THA) for patients with bilateral Crowe type IV developmental dysplasia of the hip (DDH). Methods Data for 58 patients (116 hips) with bilateral Crowe type IV DDH who had one‐stage THA performed by the same surgeon during the period of April 2008 to February 2019 were retrospectively reviewed. The mean age of the patients was 37.3 years; 5 were men and 53 were women. All patients underwent THA through the posterolateral approach using the Pinnacle acetabular cup, a ceramic‐on‐ceramic bearing, and the modular S‐ROM stem. Subtrochanteric shortening osteotomy was performed on 86/116 hips. Intraoperative conditions were recorded. Radiographic and functional outcomes were evaluated, and complications were recorded. Results All patients were followed up for an average of 71.3 ± 37.6 months (range, 12–140). The mean operative time was 276.5 ± 57.9 min (range, 175–540). The mean intraoperative blood loss was 933.6 ± 400.8 mL (range, 300–2000). The mean transfusion requirement was 1778 ± 798.0 mL (range, 575–4550). The mean length of hospital stay was 8.6 ± 3.7 days (range, 5–22). At the final follow‐up, no loosening of acetabular and femoral components was observed. No osteolysis and heterotopic ossification occurred. The mean Harris hip scores were improved from 55.4 ± 14.3 preoperatively to 91.3 ± 4.2 postoperatively (P, The study demonstrates that one‐stage bilateral THA for bilateral Crowe type IV DDH is feasible and can effectively restore hip function.

Purpose The aim of this study was to investigate the location characteristics of cystic lesions in a three-dimensional context and discuss the mechanism of formation. Methods A total of 155 femoral head computed tomography images from 94 patients diagnosed with stage II and III osteonecrosis of the femoral head were retrospectively reviewed. Three-dimensional structures of the femoral head including the cystic lesions and necrotic area were reconstructed. We divided each femoral head into eight regions to observe the positional relationship of the cystic lesions, normal areas, and necrotic areas. Results The regional distribution revealed 14 (13%), 35 (32%), 9 (8%), 25 (23%), 6 (6%), 15 (14%), 4 (4%), and 0 (0%) cystic lesions in regions Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅵ, Ⅶ, and Ⅷ, respectively. The anteromedial zone, A (Ⅰ ​+ ​Ⅲ), contained 22% of the lesions, anterolateral zone, B (Ⅱ ​+ ​Ⅳ), contained 54%, posteromedial zone, C (Ⅴ +Ⅶ), contained 9% of the lesions, and posterolateral zone, D (Ⅵ ​+ ​Ⅷ), contained 15% of the lesions. Most of the cystic lesions (78%) were located between the normal and necrotic areas; 18% of cystic lesions were in the necrotic area ​and 4% were in the normal area. Conclusions Cystic lesions most often occur at the junction of the necrotic ​and normal areas and are most commonly located in the anterolateral femoral head, which is similar to the distribution of the stress concentration region. The translational potential of this article The study showed the location characteristics of cystic lesions in osteonecrosis of femoral head, which suggested that the formation of cystic lesions may be related to stress and could accelerate the collapse of femoral head. The results can support further research on cystic lesions and provide a reference for doctors' treatment strategies for patients with osteonecrosis of femoral head.

Background The dedifferentiation of chondrocytes and the unstable chondrogenic differentiation status of pluripotent mesenchymal stem cells (MSCs) are immense issues in cell-based articular cartilage repair and regenerative strategies. Here, to improve the cartilage characteristics of seed cells, a double biomimetic acellular cartilage extracellular matrix (ACECM)-oriented scaffold was used to mimic the cartilage microenvironment for human umbilical cord Wharton’s jelly-derived MSCs (hWJMSCs) and primary cartilage cells (pACs) to regenerate hyaline cartilage. Methods A double biomimetic ACECM-oriented scaffold was created from the cartilage extracellular matrix of pig articular cartilage using pulverization decellularization freeze-drying procedures. hWJMSCs and pACs were co-cultured at ratios of 50:50 (co-culture group, ACCC), 0:100 (ACAC group) and 100:0 (ACWJ group) in the ACECM-oriented scaffold, and the co-culture system was implanted in a caprine model for 6 months or 9 months to repair full-thickness articular cartilage defects. The control groups, which had no cells, comprised the blank control (BC) group and the ACECM-oriented scaffold (AC) group. Gross morphology and magnetic resonance imaging (MRI) as well as histological and biomechanical evaluations were used to characterize the cartilage of the repair area. Results Relative to the control groups, both the gross morphology and histological staining results demonstrated that the neotissue of the ACCC group was more similar to native cartilage and better integrated with the surrounding tissue. Measurements of glycosaminoglycan content and Young’s modulus showed that the repair areas had more abundant cartilage-specific content and significantly higher mechanical strength in the ACCC group than in the control groups, especially at 9 months. On MRI, the T2-weighted signal of the repair area was homogeneous, and the oedema signal disappeared almost completely in the ACCC group at 9 months. HLA-ABC immunofluorescence staining demonstrated that hWJMSCs participated in the repair and regeneration of articular cartilage and escaped surveillance and clearance by the caprine immune system. Conclusion The structure and components of double biomimetic ACECM-oriented scaffolds provided a cartilage-like microenvironment for co-cultured seed cells and enhanced the biomechanics and compositions of neotissue. This co-culture system has the potential to overcome the dedifferentiation of passage chondrocytes and the unstable chondrogenic differentiation status of MSCs.

Osteonecrosis of the femoral head, an intractable but common disease that eventually triggers collapse of the femoral head, is characterized by increased osteoclast activity and markedly decreased osteoblast activity in the necrotic region of the femoral head. MicroRNA (miRNA)-214 (miR-214) may play important roles in vertebrate skeletal development by inhibiting osteoblast function by targeting activating transcription factor 4 (ATF4) and promoting osteoclast function via phosphatase and tensin homolog (PTEN). This study revealed significantly increased levels of miR-214 in necrotic regions, with commensurate changes in the numbers of its target cells (both osteoblasts and osteoclasts). To investigate whether targeting miR-214 could prevent femoral head collapse, we constructed an adeno-associated virus (AAV)-associated anti-miR-214 (AAV-anti-miR-214) and evaluated its function in vivo. AAV-anti-miR-214 promoted osteoblast activity and diminished osteoclast activity, effectively preventing collapse of the femoral head in a rat model of osteonecrosis. Keywords: miRNA-214, osteonecrosis of the femoral head, osteoblast activity, osteoclast activity

Objective: Our study reports the optimization of electrospray human bone marrow stromal cell (hBMSCs)–embedded alginate–gelatin (Alg-Gel, same as following) microspheres for the purpose of their assembly in 3D-printed poly(ε-caprolactone) (PCL) scaffold for the fabrication of a mechanically stable and biological supportive tissue engineering cartilage construct. Methods: The fabrication of the Alg-Gel microspheres using an electrospray technique was optimized in terms of polydispersity, yield of microspheres and circularity and varying fabrication conditions. PCL scaffolds were designed and printed by melt extrusion. Then, four groups were set: Alg-hBMSC microspheres cultured in the 2D well plate (Alg-hBMSCs+2D) group, Alg-Gel-hBMSC microspheres cultured in the 2D well plate (Alg-Gel-hBMSCs+2D) group, Alg-Gel-hBMSC microspheres embedded in PCL scaffold cultured in the 2D well plate (Alg-Gel-hBMSCs+2D) group and Alg-Gel-hBMSCs microspheres cultured in the 3D bioreactor (Alg-Gel-hBMSCs+3D) group. Cell viability, proliferation and chondrogenic differentiation were evaluated, and mechanical test was performed. Results: Nonaggregated, low polydispersity and almost spherical microspheres of average diameter of 200–300 μm were produced with alginate 1.5 w: v%, gelatin (Type B) concentration of 0.5 w: v % and CaCl2 coagulating bath concentration of 3.0 w: v %, using 30G needle size and 8 kV and 0.6 bar voltage and air pressure, respectively. Alginate with gelatin hydrogel improved viability and promoted hBMSC proliferation better than alginate microspheres. Interestingly, hBMSCs embedded in microspheres assembled in 3D-printed PCL scaffold and cultured in a 3D bioreactor were more proliferative in comparison to the previous two groups (p

Heterogeneity of mesenchymal stem cells (MSCs) influences the cell therapy outcome and the application in tissue engineering. Also, the application of subpopulations of MSCs in cartilage regeneration remains poorly characterized. CD146+ MSCs are identified as the natural ancestors of MSCs and the expression of CD146 are indicative of greater pluripotency and self-renewal potential. Here, we sorted a CD146+ subpopulation from adipose-derived mesenchymal stem cells (ADSCs) for cartilage regeneration. Methods: CD146+ ADSCs were sorted using magnetic activated cell sorting (MACS). Cell surface markers, viability, apoptosis and proliferation were evaluated in vitro. The molecular signatures were analyzed by mRNA and protein expression profiling. By intra-articular injections of cells in a rat osteochondral defect model, we assessed the role of the specific subpopulation in cartilage microenvironment. Finally, CD146+ ADSCs were combined with articular cartilage extracellular matrix (ACECM) scaffold for long term (3, 6 months) cartilage repair. Results: The enriched CD146+ ADSCs showed a high expression of stem cell and pericyte markers, good viability, and immune characteristics to avoid allogeneic rejection. Gene and protein expression profiles revealed that the CD146+ ADSCs had different cellular functions especially in regulation inflammation. In a rat model, CD146+ ADSCs showed a better inflammation-modulating property in the early stage of intra-articular injections. Importantly, CD146+ ADSCs exhibited good biocompatibility with the ACECM scaffold and the CD146+ cell-scaffold composites produced less subcutaneous inflammation. The combination of CD146+ ADSCs with ACECM scaffold can promote better cartilage regeneration in the long term. Conclusion: Our data elucidated the function of the CD146+ ADSC subpopulation, established their role in promoting cartilage repair, and highlighted the significance of cell subpopulations as a novel therapeutic for cartilage regeneration.

Background: The repair of large bone defects remains challenging for orthopaedic surgeons. Bone grafting remains the method of choice; such grafts fill spaces and enhance bone repair. Therapeutic agents also aid bone healing. The objective of this study is to develop a composite bioactive scaffold composed of polylactide-coglycolide (PLGA) and tricalcium phosphate (TCP) (the basic carrier) incorporating osteogenic, bioactive magnesium metal powder (Mg). Method: Porous PLGA/TCP scaffolds incorporating Mg were fabricated using a low-temperature rapid-prototyping process. We term the PLGA/TCP/Mg porous scaffold (hereafter, PPS). PLGA/TCP lacking Mg served as the control material when evaluating the efficacy of PPS. A total of 36 New Zealand white rabbits were randomly divided into blank, PLGA/TCP (P/T) and PPS group, with 12 rabbits in each group. We established bone defects 15 mm in length in rabbit radii to evaluate the in vivo osteogenic potential of the bioactive scaffold in terms of the direct controlled release of osteogenic Mg ion during in vivo scaffold degradation. Radiographs of the operated radii were taken immediately after implantation and then at 2, 4, 8 and 12 weeks. Micro-computed tomography of new bone formation and remaining scaffold and histological analysis were performed at 4, 8, 12 weeks after operation. Results: X-ray imaging performed at weeks 4, 8 and 12 post-surgery revealed more newly formed bone within defects implanted with PPS and PLGA/TCP scaffolds than blank group (p < 0.05). And micro-computed tomography performed at weeks 4 and 8 after surgery revealed more newly formed bone within defects implanted with PPS scaffolds than PLGA/TCP scaffolds (p

In situ tissue regeneration by homing endogenous reparative cells to the injury site has been extensively researched as a promising alternative strategy to facilitate tissue repair. In this study, a promising scaffolding system DCM-RAD/SKP, which integrated a decellularized cartilage matrix (DCM)-derived scaffold with a functionalized self-assembly Ac-(RADA)4-CONH2/Ac-(RADA)4GGSKPPGTSS-CONH2 (RAD/SKP) peptide nanofiber hydrogel, was designed for repairing rabbit osteochondral defect. In vitro experiments showed that rabbit bone marrow stem cells migrated into and have higher affinity toward the functional scaffolding system DCM-RAD/SKP than the control scaffolds. One week after in vivo implantation, the functional scaffolding system DCM-RAD/SKP facilitated the recruitment of endogenous mesenchymal stem cells within the defect site. Moreover, gene expression analysis indicated that the DCM-RAD/SKP promoted chondrogenesis of the recruited cells. In vivo results showed that the DCM-RAD/SKP achieved superior ...

Objectives The incidence of acute Achilles tendon rupture appears to be increasing. The aim of this study was to summarize various therapies for acute Achilles tendon rupture and discuss their relative merits. Methods A PubMed search about the management of acute Achilles tendon rupture was performed. The search was open for original manuscripts and review papers limited to publication from January 2006 to July 2017. A total of 489 papers were identified initially and finally 323 articles were suitable for this review. Results The treatments of acute Achilles tendon rupture include operative and nonoperative treatments. Operative treatments mainly consist of open repair, percutaneous repair, mini-open repair, and augmentative repair. Traditional open repair has lower re-rupture rates with higher risks of complications. Percutaneous repair and mini-open repair show similar re-rupture rates but lower overall complication rates when compared with open repair. Percutaneous repair requires vigilance against nerve damage. Functional rehabilitation combining protected weight-bearing and early controlled motion can effectively reduce re-rupture rates with satisfactory outcomes. Biological adjuncts help accelerating tendon healing by adhering rupture ends or releasing highly complex pools of signalling factors. Conclusion The optimum treatment for complete rupture remains controversial. Both mini-open repair and functional protocols are attractive alternatives, while biotherapy is a potential future development. Cite this article: X. Yang, H. Meng, Q. Quan, J. Peng, S. Lu, A. Wang. Management of acute Achilles tendon ruptures: A review. Bone Joint Res 2018;7:561–569. DOI: 10.1302/2046-3758.710.BJR-2018-0004.R2.

Background Centrifugation is used to remove the color interference by erythrocytes in blood-synovial fluid samples before leukocyte esterase (LE) strip testing. However, the impact of centrifugation requires further study. Methods From April 2016 to October 2017, 133 (53 infected and 80 noninfected) patients were included in this study. One drop of synovial fluid was applied to LE strips before and after centrifugation in 110 cases. The other 23 cases could not be read without centrifugation due to the color disturbance caused by blood contamination. The results were recorded after approximately 3 minutes according to different color grades on a color chart, including grade 3 (++), grade 2 (+), and grade 1 (others). Results After centrifugation, almost every sample was lighter in color than before. Although most results changed inconspicuously and remained in the same grade, 18.6% (8/43) and 17.9% (12/67) of cases were downgraded in the periprosthetic joint infection and non-periprosthetic joint infection groups, respectively. Before centrifugation, when grade 3 (++) was used as the positive threshold, the sensitivity and specificity were 97.7% (86.2%-99.9%) and 100% (94.3%-100%), respectively. After centrifugation, when grades 2 and 3 (+ and ++, respectively) were used as the positive threshold, the sensitivity and specificity were 92.5% (80.9%-97.6%) and 100% (94.3%-100%), respectively. Conclusions The influence of centrifugation should be considered when interpreting the LE strip test results. For cases without centrifugation, we recommended using ++ as the positive threshold, while for cases using centrifugation, the threshold should be reduced to both ++ and +.

Articular cartilage defects have very limited self-repair potential, and traditional bone marrow-stimulating therapy is not effective. Cartilage tissue engineering using bone marrow mesenchymal stem cells (BMSCs) and adipose tissue-derived mesenchymal stem cells (ADSCs) is considered an attractive treatment for cartilage lesions and osteoarthritis. However, studies proved that both BMSCs and ADSCs have their own advantages and shortcomings, including their sources, isolation methods, characterizations and differentiation potential. Understanding the properties and differences between ADSCs and BMSCs is important for clinical application in cartilage regeneration. This review provides an overview of BMSCs and ADSCs based on their characterization, isolation. Then, we summarized their differentiation potential in different experimental conditions. Finally, we discuss the applications of BMSCs and ADSCs in scaffold-free and scaffold-based cartilage tissue engineering. Based on different properties of BMSCs and ADSCs, and patient's physical condition, a more suitable therapeutic strategy can be selected.

Even small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP). We hypothesized that increased recruitment of endogenous stem cells by the composite scaffold could enhance cartilage regeneration. Methods: To test our hypothesis, in vitro proliferation, attachment and chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) were tested to confirm the bioactivities of the functionalized peptide hydrogel. The composite scaffold was then implanted into full-thickness cartilage defects on rabbit knee joints for cartilage repair, in comparison with microfracture or other sample groups. Stem cell recruitment was monitored by dual labeling with CD29 and CD90 under confocal microcopy at 1 week after implantation, followed by chondrogenic differentiation examined by qRT-PCR. Repaired tissue of the cartilage defects was evaluated by histological and immunohistochemistry staining, microcomputed tomography (micro-CT) and magnetic resonance imaging (MRI) at 3 and 6 months post-surgery. Macroscopic and histological scoring was done to evaluate the optimal in vivo repair outcomes of this composite scaffold. Results: The functionalized SAP hydrogels could stimulate rabbit MSC proliferation, attachment and chondrogenic differentiation during in vitro culture. At 7 days after implantation, increased recruitment of MSCs based on CD29+ /CD90+ double-positive cells was found in vivo in the composite hydrogel scaffold, as well as upregulation of cartilage-associated genes (aggrecan, Sox9 and type II collagen). After 3 and 6 months post-surgery, the articular cartilage defect in the composite scaffold-treated group was fully covered with cartilage-like tissue with a smooth surface, which was similar to the surrounding native cartilage, according to the results of histological and immunohistochemistry staining, micro-CT and MRI analysis. Macroscopic and histological scoring confirmed that the quality of cartilage repair was significantly improved with implantation of the composite scaffold at each timepoint, in comparison with microfracture or other sample groups. Conclusion: Our findings demonstrated that the composite scaffold could enhance endogenous stem cell homing and chondrogenic differentiation and significantly improve the therapeutic outcome of chondral defects. The present study provides a promising approach for in vivo cartilage repair without cell transplantation. Optimization of this strategy may offer great potential and benefits for clinical application in the future.

Background Spontaneous recovery from articular cartilage injury is difficult, and the ongoing progression of disease can eventually lead to osteoarthritis. Currently, there is no effective non-surgical treatment for articular cartilage injury. Arthroscopic debridement and microfracture surgery are performed for fibrocartilage repair. But fibrocartilage is different from normal articular cartilage, and functional recovery is not satisfactory. Therefore, it is necessary to develop more effective techniques for articular cartilage repair. Progress in material science, cell biology, biomechanics, and bioreactor technology has allowed the development of biomimetic, tissue-engineered osteochondral composites that have shown potential for the repair of damaged cartilage. We prepared biomimetic, tissue-engineered cartilage scaffolds optimized for biochemical composition and structural characteristics. Based on the experience of our pre-clinical studies on animals, a human articular cartilage acellular matrix scaffold was prepared and is in clinical use. The combination of autologous chondrocytes and scaffolds has shown satisfactory results in repairing cartilage defects in preliminary experiments. Methods This is a prospective randomized controlled trial. One hundred patients with full-thickness cartilage injury of the knee will be randomly divided into two groups to receive treatment with either tissue-engineered cartilage constructed using biomimetic cartilage extracellular-matrix-oriented scaffolds combined with autologous chondrocytes, or arthroscopic debridement and microfracture surgery. There will be five visiting time points: at baseline, then at 3, 6, 12, and 18 months postoperatively. The primary outcome will be therapeutic efficacy as assessed by the Lysholm score at 12 months postoperatively. The secondary outcomes will be the International Knee Documentation Committee score, Visual Analog Scale score, and cartilage injury and repair as assessed by magnetic resonance imaging as well as the incidence of postoperative adverse events. Discussion This trial will attempt to verify the use of tissue-engineered cartilage constructed using autologous chondrocytes combined with allogeneic, acellular cartilage matrix for the repair of cartilage defects, thereby providing favorable evidence for its use in clinical practice. Trial registration ClinicalTrials.gov, identifier: NCT02770209. Registered on 11 May 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2251-6) contains supplementary material, which is available to authorized users.

Background Knee osteoarthritis (KOA) is the most prevalent form of knee joint disease and characterized by the progressive degeneration of articular cartilage. Although pathology of KOA remains unknown, genetic factors are considered to be the major cause. Asporin is a group of biologically active components of extracellular matrix (ECM) in articular cartilage, and asporin gene (ASPN) D-repeat polymorphism was reported to be associated with KOA. Thus, our meta-analysis is aimed at investigation of the association between asporin D-repeat polymorphism and susceptibility of KOA. Methods We gathered data from MEDLINE, Embase, OVID, and ScienceDirect to search relevant published epidemiological studies through April 2017. Compared with previous studies, our meta-analysis is the first study to investigate the association of ASPN D15, D16, and D17 alleles and KOA susceptibility by ethnic- and sex-stratified subgroup analysis. Results We found no significant association between D15 allele and susceptibility to KOA (OR = 1.05, 95% CI 0.95–1.17) in overall population. The same results were observed in the analysis of D16 (OR = 1.01, 95% CI 0.80–1.28) and D17 alleles (OR = 1.28, 95% CI 0.91–1.80). The ethnic- and sex-subgroup analyses did not alter the ORs. However, significant association was detected in the sensitivity analysis of D17 in overall population (OR = 1.05, 95% CI 0.95–1.17) and Asian population (OR = 1.78, 95% CI 1.02–3.11, P

Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering.

Freeze-dried and irradiated allograft bone (FIAB) is more easily impacted than fresh-frozen allograft bone (FAB), but has weaker incorporation efficiency. We combined FIAB with fresh autologous coagula to enhance donor-host incorporation after impaction during hip revision.Thirty adult male Sprague-Dawley (SD) rats were sacrificed for bone allograft harvesting, and nine male rats were subjected to ectopic bone allograft implantation. For each rat, the container on the left (study) side was filled with freeze-dried allograft bone powder and fresh autologous blood coagula, whereas the right (control) side was filled with freeze-dried allograft bone powder and physiological saline. The extent of angiogenesis (VEGFα) was investigated at postoperative weeks 1, 4, and 8. The deformability of the material was evaluated by performing a confined-impaction mechanical test.At postoperative weeks 4 and 8, angiogenesis within FIAB on the left side was more pronounced than that on the right side. At postoperative week 1, the left side showed significantly higher VEGFα expression than that on the right side. The delta ratios of compression of the allografts were found to be influenced by bone height and impaction frequency, but not by stiffness or elastic modulus (EM).Supplementation with fresh autologous coagula promoted angiogenesis within the FIABs. Moreover, FIABs were equivalent to FABs in terms of deformability.

The crosstalk between vascularization and nerve regeneration in the peripheral nervous system has recently been suggested to play an important role in the treatment of peripheral nerve injury. Regenerative strategies via synergistic delivery of multiple biochemical cues have received growing attention, especially the combination of pro-angiogenic factors and neurotrophic factors. Here we developed a self-assembling peptide nanofiber hydrogel dual-functionalized with vascular endothelial growth factor (VEGF)- and brain-derived neurotrophic factor (BDNF)-mimetic peptide epitopes for peripheral nerve reconstruction. It could simultaneously present VEGF- and BDNF-mimetic peptide epitopes and provides a three-dimensional (3D) neurovascular microenvironment for endothelial cell and neural cell growth. In vitro cellular experiments showed that the functionalized peptide hydrogel scaffold effectively promoted the pro-myelination of Schwann cell, as well as the adhesion and proliferation of endothelial cell compared with scaffolds presenting VEGF- or BDNF-mimetic peptide epitope alone. When implanted in a rat model to bridge a critical-size sciatic nerve gap in vivo, the functionalized peptide hydrogel significantly improved the number of newly formed blood vessels, the density of regenerating axons, the morphometric analysis of the regenerated muscles and the electrophysiological findings, indicating the synergistic effect of the two bioactive motifs on peripheral nerve regeneration. Collectively, constructing an artificial neurovascular microenvironment in the lesion area by using the functionalized self-assembling peptide nanofiber hydrogel may have a great potential for promoting nerve tissue engineering and regeneration in other tissues.

Axonal degeneration is an early hallmark of nerve injury and many neurodegenerative diseases. The discovery of the Wallerian degeneration slow mutant mouse, in which axonal degeneration is delayed, revealed that Wallerian degeneration is an active progress and thereby illuminated the mechanisms underlying axonal degeneration. Nicotinamide mononucleotide adenylyltransferase 2 and sterile alpha and armadillo motif-containing protein 1 play essential roles in the maintenance of axon integrity by regulating the level of nicotinamide adenine dinucleotide, which seems to be the key molecule involved in the maintenance of axonal health. However, the function of nicotinamide mononucleotide remains debatable, and we discuss two apparently conflicting roles of nicotinamide mononucleotide in Wallerian degeneration. In this article, we focus on the roles of these molecules in the initiation phase of Wallerian degeneration to improve our understanding of the mechanisms underpinning this phenomenon.

Bone defects are very common, and there has been a great deal of research in the field of orthopedics to find ideal materials to repair such defects. Nanohydroxyapatite is a good bone substitute material; it has a number of structural similarities to natural bone, can promote new bone formation, is noncytotoxic, and has good biodegradability and biocompatibility. The use of composite and polymeric biomaterials can overcome the problems associated with the brittleness and weak mechanical properties of nanohydroxyapatite. Nanohydroxyapatite and its composite biomaterials were confirmed to play important roles in bone defect repair. This review presents a comparison of research regarding use of nanohydroxyapatite and its composite biomaterials in repairing bone defects. The goal is to identify the artificial bone substitute materials with the best biocompatibility and clinical repairing effects for various individuals and clinical situations.

Osteoarthritis (OA) is a type of chronic joint disease that is characterized by the degeneration and loss of articular cartilage and hyperplasia of the synovium and subchondral bone. There is reasonable knowledge about articular cartilage physiology, biochemistry, and chondrocyte metabolism. However, the etiology and pathogenesis of OA remain unclear and need urgent clarification to guide the early diagnosis and treatment of OA. Extracellular vesicles (EVs) are small membrane-linking particles that are released from cells. In recent decades, several special biological properties have been found in EV, especially in terms of cartilage. Autophagy plays a critical role in the regulation of cellular homeostasis. Likewise, more and more research has gradually focused on the effect of autophagy on chondrocyte proliferation and function in OA. The synthesis and release of EV are closely associated with autophagy. At the same time, both EV and autophagy play a role in OA development. Based on the mechanism of EV and autophagy in OA development, EV may be beneficial in the early diagnosis of OA; on the other hand, the combination of EV and autophagy-related regulatory drugs may provide insight into possible OA therapeutic strategies.

Gene therapy constitutes a promising strategy for the treatment of osteoarthritis (OA). We assessed the use of electroporation (EP) of non-viral gene vectors, and compared its efficacy with that of adeno-associated virus (AAV) vectors. EP- and AAV-mediated delivery of human interleukin-1 receptor antagonist (hIL-1Ra) was localized performed in the joints of rats following induction of OA. mRNA levels for hIL-1Ra, IL-1β, TNF-α, MMP-13 and ADAMTS-4 in the cartilage and synovial tissues were analyzed. Structural analyses of the subchondral bone at the medial femoral condyle were performed by Micro-CT after treatment. Knee joint specimens were staining with hematoxylin and eosin and Saffron O. Induction of hIL-1Ra by both EP and AAV inhibited inflammatory-induced sub-chondral bone reconstruction, and effectively suppressed IL-1β activity, as evidenced by decreased expression of MMP-13 and ADAMTS-4. Histological analyses revealed significant protection of cartilage, proteoglycan by EP and AAV. hIL-1Ra expression was similar in both the EP and AAV groups. Notably, this gene is not easier degraded transduced by EP compared with AAV. Taken together, these results show that EP offers transfection efficiency comparable to that of AAV, with the potential for longer gene expression, making EP a promising candidate for efficient non-viral delivery of OA gene therapy.

The extracellular matrix, which includes collagens, laminin, or fibronectin, plays an important role in peripheral nerve regeneration. Recently, a Schwann cell-derived extracellular matrix with classical biomaterial was used to mimic the neural niche. However, extensive clinical use of Schwann cells remains limited because of the limited origin, loss of an autologous nerve, and extended in vitro culture times. In the present study, human umbilical cord-derived mesenchymal stem cells (hUCMSCs), which are easily accessible and more proliferative than Schwann cells, were used to prepare an extracellular matrix. We identified the morphology and function of hUCMSCs and investigated their effect on peripheral nerve regeneration. Compared with a non-coated dish tissue culture, the hUCMSC-derived extracellular matrix enhanced Schwann cell proliferation, upregulated gene and protein expression levels of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor in Schwann cells, and enhanced neurite outgrowth from dorsal root ganglion neurons. These findings suggest that the hUCMSC-derived extracellular matrix promotes peripheral nerve repair and can be used as a basis for the rational design of engineered neural niches.

Flexible nerve guide conduits (NGCs) are desired in peripheral nerve reconstruction near the joints. Inspired by the engineered structure of the helical tube, we addressed the problems of conventional NGCs often mentioned in clinical feedback. We developed a type of helix-flexible NGC (HF-NGC) and evaluated its mechanical properties as well as its flexibility, and it performed excellently during in vitro tests. During the in vivo tests, HF-NGCs and conventional nonflexible NGCs (NF-NGCs) were implanted in a rat sciatic nerve defect model. A short-term investigation showed that Schwan cells (SCs) infiltrated into the helical groove, and most of them belonged to the activated SC type. Compared with NF-NGCs, HF-NGCs had fewer apoptotic SCs. In the long term investigation, HF-NGCs maintained flexibility in vivo after 3 months. Analyses of the morphometric parameters of nerve fibers and the static sciatic index showed that the HF-NGCs had similar regeneration outcomes to those of traditional NF-NGCs. Therefore, this style of HF-NGC could be used to repair peripheral nerve damage in a cross-joint region with less tension during operation and easy to postoperative rehabilitation. We believe that the HF-NGC is a potentially valuable candidate for clinical use.

Background Bone marrow is an important source of stem cells, which can promote bone fracture healing. Methods We investigated the optimal time to inject bone marrow mesenchymal stem cells (BMSCs) in a C57 murine unilateral, transverse, femur fracture model. BMSCs transfected with red fluorescent protein (RFP-BMSCs) were injected via the tail vein on day 1, 7, or 14 post-fracture. AMD3100 (inhibitor of stromal cell-derived factor 1 [SDF-1]) was also injected before RFP-BMSCs in one group for comparison; a control group received saline injections. RFP-BMSC migration and fracture healing were evaluated by in vivo fluorescence assay. Micro-CT was performed and mechanical testing and histological analysis. Chemokine levels were evaluated by quantitative real-time PCR and western blotting. Results Following injection on day 7 post-fracture, RFP-BMSCs more frequently homed to the fracture site and remained for a longer duration. Bone volume and bone mineral density were increased when BMSCs were injected on day 7 post-fracture (P

Background: Benefits of yoga practice in patients with knee osteoarthritis and rheumatoid arthritis remains controversial. This study performs a meta-analysis to quantify the efficiency of yoga exercise for patients pain reduction, functional recovery, and general wellbeing. Methods: A computerized search of PubMed and Embase was performed to identify relevant studies. The outcome measures were pain, stiffness, and physical function. Two investigators identified eligible studies and extracted data independently. The quality of citations was measured using Jadad score. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for pain, musculoskeletal impairment, quality of life, general wellbeing, and mental wellbeing. Results: A total of 13 clinical trials involving 1557 patients with knee osteoarthritis and rheumatoid arthritis were included in final meta-analysis with the average Jadad score 2.8. The SMD was −0.98 (95% CI −1.18, −0.78, P

To observe the feasibility of acellular cartilage extracellular matrix (ACECM) oriented scaffold combined with chondrocytes to construct tissue engineered cartilage.Chondrocytes from the healthy articular cartilage tissue of pig were isolated, cultured, and passaged. The 3rd passage chondrocytes were labeled by PKH26. After MTT demonstrated that PKH26 had no influence on the biological activity of chondrocytes, labeled and unlabeled chondrocytes were seeded on ACECM oriented scaffold and cultivated. The adhesion, growth, and distribution were evaluated by gross observation, inverted microscope, and fluorescence microscope. Scanning electron microscope was used to observe the cellular morphology after cultivation for 3 days. Type Ⅱ collagen immunofluorescent staining was used to check the secretion of extracellular matrix. In addition, the complex of labeled chondrocytes and ACECM oriented scaffold (cell-scaffold complex) was transplanted into the subcutaneous tissue of nude mouse. After transplantation, general physical conditions of nude mouse were observed, and the growth of cell-scaffold complex was observed by molecular fluorescent living imaging system. After 4 weeks, the neotissue was harvested to analyze the properties of articular cartilage tissue by gross morphology and histological staining (Safranin O staining, toluidine blue staining, and typeⅡcollagen immunohistochemical staining).After chondrocytes that were mainly polygon and cobblestone like shape were seeded and cultured on ACECM oriented scaffold for 7 days, the neotissue was translucency and tenacious and cells grew along the oriented scaffold well by inverted microscope and fluorescence microscope. In the subcutaneous microenvironment, the cell-scaffold complex was cartilage-like tissue and abundant cartilage extracellular matrix (typeⅡcollagen) was observed by histological staining and typeⅡcollagen immunohistochemical staining.ACECM oriented scaffold is benefit to the cell adhesion, proliferation, and oriented growth and successfully constructes the tissue engineered cartilage in nude mouse model, which demonstrates that the ACECM oriented scaffold is promise to be applied in cartilage tissue engineering.探讨脱细胞软骨细胞外基质（acellular cartilage extracellular matrix, ACECM）取向支架复合软骨细胞构建组织工程软骨的可行性。.取市售猪关节软骨组织，分离培养关节软骨细胞并传代。取第 3 代软骨细胞行 PKH26 荧光标记，MTT 检测标记对细胞增殖无影响后，分别取标记及未标记的软骨细胞复合 ACECM 取向支架并体外培养后，大体观察支架形态，倒置显微镜、荧光显微镜观察软骨细胞在支架中的黏附、生长和分布情况，扫描电镜观察支架中细胞形态，Ⅱ型胶原免疫荧光染色观察软骨细胞外基质分泌情况。将 PKH26 标记的软骨细胞-支架复合物植入裸鼠背部皮下腔隙，术后观察裸鼠一般情况，4 周后分子荧光活体成像系统无创伤性评估细胞-支架复合物生长情况，取材行大体观察以及番红 O、甲苯胺蓝、Ⅱ型胶原免疫组织化学染色观察，评价形成软骨组织的能力。.细胞-支架复合物体外培养 7 d，大体观察呈半透明并具有一定硬度；倒置显微镜和荧光显微镜观察软骨细胞在支架上能良好黏附生长，并沿支架管道方向生长，分泌Ⅱ型胶原。细胞-支架复合物植入裸鼠皮下后，分子荧光活体成像系统观察示细胞均存活；术后 4 周，大体观察见复合物呈类软骨样组织，组织学染色及Ⅱ型胶原免疫组织化学染色示细胞周围软骨细胞外基质分泌，可见“陷窝”样结构形成。.ACECM 取向支架有利于软骨细胞的黏附、增殖及取向性分布类似于正常软骨结构，并在裸鼠皮下成功异位构建组织工程软骨。.