Tannic Acid-Modified Decellularized Tendon Scaffold with Antioxidant and Anti-Inflammatory Activities for Tendon Regeneration.

Tendon regeneration is greatly influenced by the oxidant and the inflammatory microenvironment. Persistent inflammation during the tendon repair can cause matrix degradation, tendon adhesion, and excessive accumulation of reactive oxygen species (ROS), while excessive ROS affect extracellular matrix remodeling and tendon integration. Herein, we used tannic acid (TA) to modify a decellularized tendon slice (DTS) to fabricate a functional scaffold (DTS-TA) with antioxidant and anti-inflammatory properties for tendon repair. The characterizations and cytocompatibility of the scaffolds were examined in vitro. The antioxidant and anti-inflammatory activities of the scaffold were evaluated in vitro and further studied in vivo using a subcutaneous implantation model. It was found that the modified DTS combined with TA via hydrogen bonds and covalent bonds, and the hydrophilicity, thermal stability, biodegradability, and mechanical characteristics of the scaffold were significantly improved. Afterward, the results demonstrated that DTS-TA could effectively reduce inflammation by increasing the M2/M1 macrophage ratio and interleukin-4 (IL-4) expression, decreasing the secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), as well as scavenging excessive ROS in vitro and in vivo. In summary, DTS modified with TA provides a potential versatile scaffold for tendon regeneration.

Decellularized tendon scaffolds loaded with collagen targeted extracellular vesicles from tendon-derived stem cells facilitate tendon regeneration.

Stem cell-based treatment of tendon injuries remains to have some inherent issues. Extracellular vesicles derived from stem cells have shown promising achievements in tendon regeneration, though their retention in vivo is low. This study reports on the use of a collagen binding domain (CBD) to bind extracellular vesicles, obtained from tendon-derived stem cells (TDSCs), to collagen. CBD-extracellular vesicles (CBD-EVs) were coupled to decellularized bovine tendon sheets (DBTS) to fabricate a bio-functionalized scaffold (CBD-EVs-DBTS). Our results show that thus obtained bio-functionalized scaffolds facilitate the proliferation, migration and tenogenic differentiation of stem cells in vitro. Furthermore, the scaffolds promote endogenous stem cell recruitment to the defects, facilitate collagen deposition and improve the biomechanics of injured tendons, thus resulting in functional regeneration of tendons.

Constructing a highly bioactive tendon-regenerative scaffold by surface modification of tissue-specific stem cell-derived extracellular matrix.

Developing highly bioactive scaffold materials to promote stem cell migration, proliferation and tissue-specific differentiation is a crucial requirement in current tissue engineering and regenerative medicine. Our previous work has demonstrated that the decellularized tendon slices (DTSs) are able to promote stem cell proliferation and tenogenic differentiation in vitro and show certain pro-regenerative capacity for rotator cuff tendon regeneration in vivo. In this study, we present a strategy to further improve the bioactivity of the DTSs for constructing a novel highly bioactive tendon-regenerative scaffold by surface modification of tendon-specific stem cell-derived extracellular matrix (tECM), which is expected to greatly enhance the capacity of scaffold material in regulating stem cell behavior, including migration, proliferation and tenogenic differentiation. We prove that the modification of tECM could change the highly aligned surface topographical cues of the DTSs, retain the surface stiffness of the DTSs and significantly increase the content of multiple ECM components in the tECM-DTSs. As a result, the tECM-DTSs dramatically enhance the migration, proliferation as well as tenogenic differentiation of rat bone marrow-derived stem cells compared with the DTSs. Collectively, this strategy would provide a new way for constructing ECM-based biomaterials with enhanced bioactivity for in situ tendon regeneration applications.

Biomechanically and biochemically functional scaffold for recruitment of endogenous stem cells to promote tendon regeneration.

Tendon regeneration highly relies on biomechanical and biochemical cues in the repair microenvironment. Herein, we combined the decellularized bovine tendon sheet (DBTS) with extracellular matrix (ECM) from tendon-derived stem cells (TDSCs) to fabricate a biomechanically and biochemically functional scaffold (tECM-DBTS), to provide a functional and stem cell ECM-based microenvironment for tendon regeneration. Our prior study showed that DBTS was biomechanically suitable to tendon repair. In this study, the biological function of tECM-DBTS was examined in vitro, and the efficiency of the scaffold for Achilles tendon repair was evaluated using immunofluorescence staining, histological staining, stem cell tracking, biomechanical and functional analyses. It was found that tECM-DBTS increased the content of bioactive factors and had a better performance for the proliferation, migration and tenogenic differentiation of bone marrow-derived stem cells (BMSCs) than DBTS. Furthermore, our results demonstrated that tECM-DBTS promoted tendon regeneration and improved the biomechanical properties of regenerated Achilles tendons in rats by recruiting endogenous stem cells and participating in the functionalization of these stem cells. As a whole, the results of this study demonstrated that the tECM-DBTS can provide a bionic microenvironment for recruiting endogenous stem cells and facilitating in situ regeneration of tendons.

Fabrication and characterization of a pro-angiogenic hydrogel derived from the human placenta.

Various hydrogels derived from the xenogeneic extracellular matrix (ECM) have been utilised to promote the repair and reconstruction of numerous tissues; however, there are few studies on hydrogels derived from allogeneic specimens. Human placenta derived hydrogels have been used in the therapy of ischaemic myocardium; however, their physicochemical properties and effects on cellular behaviour remain elusive. As the human placenta retains pro-angiogenic growth factors, it is hypothesized that the placenta hydrogels possess the potential to improve angiogenesis. In this study, a soluble decellularized human placenta matrix generated using a modified method could be stored in a powder form and could be used to form a hydrogel in vitro. Effective decellularization was evaluated by analysing the DNA content and histology images. The placenta hydrogel exhibited a fibrous porous morphology and was injectable. Fourier transform infrared (FTIR) spectroscopy revealed that the placenta hydrogel contained both collagen and sulfated glycosaminoglycans (GAGs). In addition, immunofluorescence imaging and enzyme-linked immunosorbent assay (ELISA) showed that the placenta hydrogel retained pro-angiogenic growth factors, including VEGF and bFGF, and transforming growth factor-ß1 (TGF-ß1). Further in vitro and in vivo analyses confirmed that the placenta hydrogel exerted better pro-angiogenic effects than a collagen type I hydrogel. Histological data also showed that the placenta hydrogels did not elicit a grave inflammatory response. In conclusion, the results suggest that placenta hydrogels may be deemed an attractive scaffold for regenerative medicine applications, especially in promoting vessel formation.

[Research progress of interfacial tissue engineering in rotator cuff repair].

OBJECTIVE: To summarize the research progress of interfacial tissue engineering in rotator cuff repair. METHODS: The recent literature at home and abroad concerning interfacial tissue engineering in rotator cuff repair was analysed and summarized. RESULTS: Interfacial tissue engineering is to reconstruct complex and hierarchical interfacial tissues through a variety of methods to repair or regenerate damaged joints of different tissues. Interfacial tissue engineering in rotator cuff repair mainly includes seed cells, growth factors, biomaterials, oxygen concentration, and mechanical stimulation. CONCLUSION: The best strategy for rotator cuff healing and regeneration requires not only the use of biomaterials with gradient changes, but also the combination of seed cells, growth factors, and specific culture conditions (such as oxygen concentration and mechanical stimulation). However, the clinical transformation of the relevant treatment is still a very slow process.

Enhancement of Migration and Tenogenic Differentiation of Macaca Mulatta Tendon-Derived Stem Cells by Decellularized Tendon Hydrogel.

Decellularized tendon hydrogel from human or porcine tendon has been manufactured and found to be capable of augmenting tendon repair in vivo. However, no studies have clarified the effect of decellularized tendon hydrogel upon stem cell behavior. In the present study, we developed a new decellularized tendon hydrogel (T-gel) from Macaca mulatta, and investigated the effect of T-gel on the proliferation, migration and tenogenic differentiation of Macaca mulatta tendon-derived stem cells (mTDSCs). The mTDSCs were first identified to have universal stem cell characteristics, including clonogenicity, expression of mesenchymal stem cell and embryonic stem cell markers, and multilineage differentiation potential. Decellularization of Macaca mulatta Achilles tendons was confirmed to be effective by histological staining and DNA quantification. The resultant T-gel exhibited highly porous structure or similar nanofibrous structure and approximately swelling ratio compared to the collagen gel (C-gel). Interestingly, stromal cell-derived factor-1 (SDF-1) and fibromodulin (Fmod) inherent in the native tendon extracellular matrix (ECM) microenvironment were retained and the values of SDF-1 and Fmod in the T-gel were significantly higher than those found in the C-gel. Compared with the C-gel, the T-gel was found to be cytocompatible with NIH-3T3 fibroblasts and displayed good histocompatibility when implanted into rat subcutaneous tissue. More importantly, it was demonstrated that the T-gel supported the proliferation of mTDSCs and significantly promoted the migration and tenogenic differentiation of mTDSCs compared to the C-gel. These findings indicated that the T-gel, with its retained nanofibrous structure and some bioactive factors of native tendon ECM microenvironment, represents a promising hydrogel for tendon regeneration.

Hierarchically Demineralized Cortical Bone Combined With Stem Cell-Derived Extracellular Matrix for Regeneration of the Tendon-Bone Interface.

BACKGROUND: Poor healing of the tendon-bone interface after rotator cuff repair is one of the main causes of surgical failure. Previous studies demonstrated that demineralized cortical bone (DCB) could improve healing of the enthesis. PURPOSE: To evaluate the outcomes of hierarchically demineralized cortical bone (hDCB) coated with stem cell-derived extracellular matrix (hDCB-ECM) in the repair of the rotator cuff in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: Tendon-derived stem cells (TDSCs) were isolated, cultured, and identified. Then, hDCB was prepared by the graded demineralization procedure. Finally, hDCB-ECM was fabricated via 2-week cell culture and decellularization, and the morphologic features and biochemical compositions of the hDCB-ECM were evaluated. A total of 24 rabbits (48 samples) were randomly divided into 4 groups: control, DCB, hDCB, and hDCB-ECM. All rabbits underwent bilateral detachment of the infraspinatus tendon, and the tendon-bone interface was repaired with or without scaffolds. After surgery, 8 rabbits were assessed by immunofluorescence staining at 2 weeks, and the others were assessed by micro-computed tomography (CT) examination, immunohistochemical staining, histological staining, and biomechanical testing at 12 weeks. RESULTS: TDSCs were identified to have universal stem cell characteristics including cell markers, clonogenicity, and multilineage differentiation. The hDCB-ECM contained 3 components (bone, partial DCB, and DCB coated with ECM) with a gradient of calcium and phosphorus elements, and the ECM had stromal cell-derived factor 1, biglycan, and fibromodulin. Macroscopic observations demonstrated the absence of infection and rupture around the enthesis. The results of immunofluorescence staining showed that hDCB-ECM promoted stromal cell recruitment. Results of micro-CT analysis, immunohistochemical staining, and histological staining showed that hDCB-ECM enhanced bone and fibrocartilage formation at the tendon-bone interface. Biomechanical analysis showed that the hDCB-ECM group had higher ultimate tensile stress and Young modulus than the DCB group. CONCLUSION: The administration of hDCB-ECM promoted healing of the tendon-bone interface. CLINICAL RELEVANCE: hDCB-ECM could provide useful information for the design of scaffolds to repair the tendon-bone interface, and further studies are needed to determine its effectiveness.

Segmentally Demineralized Cortical Bone With Stem Cell-Derived Matrix Promotes Proliferation, Migration and Differentiation of Stem Cells in vitro.

A recent study has shown that demineralized cortical bone (DCB) did not improve the healing of tendon-bone interface. Considering that there is a gradient of mineral content in the tendon-bone interface, we designed a segmentally demineralized cortical bone (sDCB) scaffold with two different regions: undemineralized cortical bone section within the scaffold (sDCB-B) and complete demineralized cortical bone section within the scaffold (sDCB-D), to mimic the natural structure of the tendon-bone interface. Furthermore, the extracellular matrix (ECM) from tendon-derived stem cells (TDSCs) was used to modify the sDCB-D region of sDCB to construct a novel scaffold (sDCB-ECM) for enhancing the bioactivity of the sDCB-D. The surface topography, elemental distribution, histological structure, and surface elastic modulus of the scaffold were observed using scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, histological staining and atomic force microscopy. Cell proliferation of bone marrow mesenchymal stem cells (BMSCs) and TDSCs cultured on scaffolds was evaluated using the Cell Counting kit-8, and cell viability was assessed by Live/Dead cell staining. Cell morphology was detected by fluorescent staining. The ability of the scaffolds to recruit stem cells was tested using transwell migration assay. The expression levels of bone-, cartilage- and tendon-related genes and proteins in stem cells were assessed by the polymerase chain reaction and western blotting. Our results demonstrated that there was a gradient of Ca and P elements in sDCB, and TDSC-derived ECM existed on the surface of the sDCB-D region of sDCB. The sDCB-ECM could promote stem cell proliferation and migration. Moreover, the sDCB-B region of sDCB-ECM could stimulate osteogenic and chondrogenic differentiation of BMSCs, and the sDCB-D-ECM region of sDCB-ECM could stimulate chondrogenic and tenogenic differentiation of TDSCs when compared to DCB. Our study indicated that sDCB-ECM might be a potential bioscaffold to enhance the tendon-bone interface regeneration.

Influence of the integrity of tendinous membrane and fascicle on biomechanical characteristics of tendon-derived scaffolds.

The biomechanical characteristics of tendon grafts is essential for tendon reconstructive surgery due to its great role in providing a good mechanical environment for tendon healing and regeneration. In our previous studies, the decellularized tendon slices (DTSs) and decellularized bovine tendon sheets (DBTSs) scaffolds were successfully developed. However, the influence of the integrity of tendinous membrane (endotenon and epitenon) and fascicle on biomechanical characteristics of these two scaffolds was not investigated. In this study, we assessed the integrity of tendinous membrane and fascicle of the tendon derived scaffolds and its effect on the biomechanical characteristics. The results of histological staining indicated that the DBTSs had complete endotenon and epitenon, while DTSs had no epitenon at all, only part of endotenon was remained. Furthermore, the DBTSs, and DTSs with thickness of 900 µm had complete fascicles, while DTSs with thickness less than 600 µm had almost no complete fascicles. The fibrous configuration of epitenon was well-preserved in the surface of the DBTSs but the surface ultrastructure of the DTSs was aligned collagen fibers based on scanning electron microscopy examination. The results of transmission electron microscopy showed that there was no significant difference between the DBTSs and DTSs. Mechanically, the DBTSs and DTSs with thickness of 900 µm showed similar ultimate tensile strength and stiffness to native tendon segments (NTSs). The strain at break and suture retention strength of the DBTSs showed much higher than that of the DTSs (p < 0.05). Additionally, the DBTSs showed higher ultimate load than the DTSs when these scaffolds were sutured with NTSs (p < 0.05) through the modified Kessler technique based on a uniaxial tensile test. This study demonstrated that DTSs may be used as a patch for reinforcing tendon repair, while DBTSs may be used as a bridge for reconstructing tendon defects.

A programmable, fast-fixing, osteo-regenerative, biomechanically robust bone screw.

The use of a screw for repairing defected bones is limited by the dilemma between stiffness, bioactivity and internal fixation ability in current products. For polymer bone screw, it is difficult to achieve the bone stiffness and osteo-induction. Polymer composites may enhance bioactivity and mechanical properties but sacrifice the shape memory properties enormously. Herein, we fabricated a programmable bone screw which is composed of shape memory polyurethane, hydroxyapatite and arginylglycylaspartic acid to resolve the above problem. This composite has significantly improved mechanical and shape-memory properties with a modulus of 250 MPa, a shape fixity ratio of ~90% and a shape recovery ratio of ~96%. Moreover, shape fixity and recovery ratios of the produced SMPC screw in the simulative biological condition were respectively ~80% and ~82%. The produced screw could quickly recover to its original shape in vitro within 20 s leading to easy internal fixation. Additionally, the composite could support mesenchymal stem cell survival, proliferation and osteogenic differentiation in vitro tests. It also promoted tissue growth and showed beneficial mechanical compatibility after implantation into a rabbit femoral intracondyle for 12 weeks with little inflammation. Such bone screw exhibited a fast-fixing, tightened fitting, enhanced supporting and boosted bioactivity simultaneously in the defective bone, which provides a solution to the long-standing problem for bone repairing. We envision that our composite material will provide valuable insights into the development of a new generation of bone screws with good fixation and osteogenic properties. STATEMENT OF SIGNIFICANCE: The main obstacles to a wider use of a bone screw are unsatisfied stiffness, inflammatory response and screw loosening issues. Herein, we report a programmable screw with mechanically robust, bioactive and fast-fixing performances. The shape memory polymer composite takes advantage of the component in the natural bone and possesses a stable bush-like structure inside through the covalent bonding, and thus achieve significantly improved mechanical and memory properties. Based on its shape memory effect, the produced screw was proved to offer a recovery force to surroundings and promote the bone regeneration effectively. Therefore, the composite realizes our expectations on functions through structure design and paves a practical and effective way for the development of a new generation of bone screws.

[A rapid histological preparation method for observation of morphology and composition distribution of tendon collagen fascicle and endotendinium].

OBJECTIVE: To explore a rapid histological preparation method to observe morphology and composition distribution of tendon collagen fascicle and endotendinum. METHODS: Taking porcine superflexor tendon of foot as an example, tendons were sliced into sections with 6 µm by frozen section technology, after which general observation of the section integrity was carried out. After fixed with 10% neutral buffered formalin and performed with HE staining, the tissue integrity and ice crystal formation were observed under microscope. Sections were then divided into 5 groups by different methods of dyeing. Group A: Priodic acid-Shiff (PAS) staining; group B: Masson staining; group C: reticular fibers staining; group D: immunohistochemical and immunofluorescent staining of type Ⅲ collagen; group E: the sections were baked at 65℃ for 10 minutes and stained with Masson. The composition distribution of tendon collagen fascicle and endotendinum in different groups were observed. RESULTS: From general observation, the frozen section of tendon tissue was complete and continuous. Although the tissue integrity in the tendon sections could be seen and no ice crystal was formed, the composition distribution could not be identified by HE staining. The entire tendons in groups A, B, and C were dyed, and the composition distribution of collagen fascicle and endotendinum could not be identified. The endotendinum in group D was stained weakly positive for type Ⅲ collagen alone, and the two components were differentiated dyed but the contrast was not obvious. In group E, the collagen fascicle and endotendinium were differentiated dyed and the two components in tendon tissue were clearly visible. CONCLUSION: The morphology and the composition distribution of tendon collagen fascicle and endotendinum can be characterized rapidly and accurately, using a combination of baking at 65℃ for 10 minutes and Masson staining after porcine superflexor tendons were sliced by frozen section technology.

The cytoptrotection of small intestinal submucosa-derived gel in HL-1 cells during hypoxia/reoxygenation-induced injury.

Small intestinal submucosa (SIS)-derived gel injected into infarcted myocardium has been shown to promote repair and regeneration after myocardial infarction (MI); however, the specific impact of SIS gel on cardiomyocytes remained unknown. The aim of this study was to characterise SIS gel function in hypoxia-reoxygenation (H/R)-induced cardiomyocyte damage and its potential mechanism. HL-1 cardiomyocytes seeded on SIS matrix-coated plates, SIS gel, and uncoated plates were subjected to H/R, cell viability, apoptosis, expression of caspase-3, Bcl-2, and Bax were investigated. SIS gel and SIS matrix as coating substrates markedly improved cell viability, preventing cell apoptosis compared with uncoated plates, with SIS gel yielding the best cytoprotective effects. SIS gel down-regulated expression of pro-inflammatory cytokines (TNF-α, CCL2, and IL-6) by inhibiting the JNK-mitogen-activated protein kinase (MAPK)/NF-κB pathways. Furthermore, SIS gel protected cardiomyocytes from apoptosis by activating protein kinase B (AKT) and extracellular-signal-regulated kinase (ERK) pathways, and markedly up-regulated antiapoptotic Bcl-2 expression but inhibited that of proapoptotic Bax and c-caspase 3. Together, these findings show that SIS gel could decrease H/R-induced cell apoptosis through a mechanism potentially related to its ability to regulate expression of inflammatory cytokines and antiapoptosis signalling pathways to prevent cell apoptosis. Our findings thereby shed light on the mechanism related to SIS gel therapeutic efficacy for MI.

Production and Characterization of Composite Chitosan Hydrogel Containing Extracellular Matrix Particles for Tissue Engineering Applications.

Chitosan-based hydrogels have been extensively used for tissue regeneration due to the excellent biocompatibility and biodegradability. For lack of endogenous extracellular biomacromolecules, its application is obviously limited. Because of robust biological activity, porcine small intestinal submucosa (SIS) has been considered as promising candidates to increase the bioactivity of hydrogels. Herein, a facile method for the fabrication of SIS powders (SISP)/chitosan chloride (CSCl)-ß-glycerol phosphate (GP)-hydroxyethyl cellulose (HEC) hydrogel was developed. FTIR imaging results demonstrated that SISP and CSCl could be well mixed to form porous three-dimensional SISP/CSCl composite, which underwent sol-gel phage transition from solution to non-flowing hydrogel at 37 °C. Interestingly, the sustained release of VEGF and b-FGF within the composite hydrogel was determined and no initial burst release was observed. SISP/CSCl composite supported the survival and proliferation of NIH 3T3 cells in vitro and good biocompatibility in the SD rats subcutis up to 8 weeks. Furthermore, incorporated with SISP into CSCl delayed the degradation of SISP in vivo, as characterized by histological and High-Frequency Ultrasound (HFUS) measurement. Thus, all the findings suggested that the newlydeveloped injectable and thermosensitive SISP/CSCl composite was a promising and attractive candidate for soft tissue regeneration in the minimally-invasive way.

Effects of hydrogen peroxide on biological characteristics and osteoinductivity of decellularized and demineralized bone matrices.

Due to the similar collagen composition and closely physiological relationship with soft connective tissues, demineralized bone matrices (DBMs) were used to repair the injured tendon or ligament. However, the osteoinductivity of DBMs would be a huge barrier of these applications. Hydrogen peroxide (H2 O2 ) has been proved to reduce the osteoinductivity of DBMs. Nevertheless, the biological properties of H2 O2 -treated DBMs have not been evaluated completely, while the potential mechanism of H2 O2 compromising osteoinductivity is also unclear. Hence, the purpose of this study was to characterize the biological properties of H2 O2 -treated DBMs and search for the proof that H2 O2 could compromise osteoinductivity of DBMs. Decellularized and demineralized bone matrices (DCDBMs) were washed by 3% H2 O2 for 12 h to fabricate the H2 O2 -treated DCDBMs (HPTBMs). Similar biological properties including collagen, biomechanics, and biocompatibility were observed between DCDBMs and HPTBMs. The immunohistochemistry staining of bone morphogenetic protein 2 (BMP-2) was negative in HPTBMs. Furthermore, HPTBMs exhibited significantly reduced osteoinductivity both in vitro and in vivo. Taken together, these findings suggest that the BMP-2 in DCDBMs could be the target of H2 O2 . HPTBMs could be expected to be used as a promising scaffold for tissue engineering. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

Enhancement of tenogenic differentiation of rat tendon-derived stem cells by biglycan.

Biglycan (BGN) has been identified as one of the critical components of the tendon-derived stem cells (TDSCs) niche and may be related to tendon formation. However, so far, no study has demonstrated whether the soluble BGN could induce the tenogenic differentiation of TDSCs in vitro. The aim of this study was to investigate the effect of BGN on the tenogenic differentiation of TDSCs. The proliferation and tenogenic differentiation of TDSCs exposed to different concentrations of BGN (0, 50, 100, and 500 ng/ml) were determined by the live/dead cell staining assay, CCK-8 assay, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. The BGN signaling pathway of TDSCs (with and without 50 ng/ml of BGN) was determined by western blot analysis and qRT-PCR analysis. At a concentration of 50 ng/ml, BGN increased the expression of the tenogenic markers THBS-4 and TNMD at both the messenger RNA (mRNA) and protein levels. Meanwhile, 50 ng/ml of BGN inhibited the expression of the chondrogenic and osteogenic markers SOX9, ACN, and RUNX2 at both the mRNA and protein levels. Moreover, BGN (50 ng/ml) affected the expression of the components of the extracellular matrix of TDSCs. Additionally, BGN activated the Smad1/5/8 pathway as indicated by an increase in phosphorylation and demonstrated by inhibition experiments. Upregulation in the gene expression of BMP-associated receptors (BMPRII, ActR-IIa, and BMPR-Ib) and Smad pathway components (Smad4 and 8) was observed. Taken together, BGN regulates tenogenic differentiation of TDSCs via BMP7/Smad1/5/8 pathway and this regulation may provide a basic insight into treating tendon injury.

Mechanically Robust Shape Memory Polyurethane Nanocomposites for Minimally Invasive Bone Repair.

Shape memory polymers (SMPs) have great potential utility in the area of minimally invasive surgery; however, insufficient mechanical properties hinder their applications for bone defect repair, particularly in high load-bearing locations. In this study, hydroxyapatite (HA)/reduced graphene oxide (rGO) nanofillers were incorporated into a shape memory polyurethane (SMPU) to enhance its mechanical properties. Then the nanocomposite was further modified using arginyl-glycyl-aspartic acid (RGD peptide) to improve its cellular adhesion toward promoting neotissue formation and integration with surrounding bone tissue. The physical and biological properties in terms of their chemical structure, surface wettability, mechanical behaviors, shape memory performance, and cell adhesion were systematically investigated. The results demonstrated that the multimodified SMPU/HA/rGO/RGD nanocomposite significantly enhanced mechanical properties (e.g., ∼200% increase in Young's modulus and >300% enhancement in tensile strength compared with the unmodified SMPU), which might be attributed to the intercalated structure and metal affinity inside the nanocomposite. Adhesion of rabbit bone mesenchymal stem cells was clearly demonstrated on an RGD-immobilized SMPU nanocomposite surface. With an excellent shape memory behavior (e.g., 97.3% of shape fixity ratio and 98.2% of shape recovery ratio), we envision that our SMPU/HA/rGO/RGD nanocomposite can be implanted into a bone defect with a minimally invasive surgery.

Stem Cell Extracellular Matrix-Modified Decellularized Tendon Slices Facilitate the Migration of Bone Marrow Mesenchymal Stem Cells.

It is highly desirable to develop a novel scaffold that can induce stem cell migration in tendon tissue engineering and regeneration. The objective of this study is to assess the effect of stem cell extracellular matrix-modified decellularized tendon slices (ECM-DTSs) on bone marrow mesenchymal stem cells (BMSCs) migration and explore the possible molecular mechanisms. Native ECM produced by BMSCs and tendon-derived stem cells (TDSCs) was deposited on DTSs, denoted as bECM-DTSs and tECM-DTSs, respectively, and the migration of BMSCs treated with the extracts from ECM-DTSs was studied. Almost all the seeded stem cells were removed from the stem cell-DTS composites, while ECM produced by stem cells completely covered the surface of the DTSs. Significantly higher levels of chemokines, including stromal cell-derived factor-1 (SDF-1) and monocyte chemotactic protein-1 (MCP-1) were released by ECM-DTSs than by bare DTSs (p < 0.05), according to ELISA, and tECM-DTSs exhibited the highest release within 72 h. bECM-DTSs and tECM-DTSs markedly improved BMSCs migration compared to bare DTSs, with tECM-DTSs yielding the best recruitment effects. The ECM-DTSs led to early cytoskeletal changes compared to bare DTSs (p < 0.05). Migration-related gene and protein expression was significantly up-regulated in BMSCs treated with ECM-DTSs via the PI3K/AKT signaling pathway (p < 0.05), indicating that ECM-DTSs could enhance BMSCs migration via the PI3K/AKT signal pathway, and the effect of tECM-DTSs on BMSCs migration is superior to that of bECM-DTSs. This may provide the experimental and theoretical evidence for using stem cell-derived ECM-modified scaffold as a novel approach to recruit stem cells.

Combined use of Kirschner wires and hinged external fixator for capitellar and trochlear fractures: a minimum 24-month follow-up.

BACKGROUND: Open reduction and internal fixation is the adequate treatment for capitellar and trochlear fractures. Given the low incidence of this type of fractures, it is difficult to constitute a universally accepted method for fixation. Thus, we hypothesised that combined use of Kirschner wires (K-wires), absorbable rods and sutures for fixation and post-operative hinged external fixator for early rehabilitation exercise can restore elbow joint function well. METHODS: This retrospective study included 20 patients with a mean age of 48.3 (range 16-76) years. According to the Dubberley classification, fractures were classified on plain radiographs, computed tomography images and intra-operative findings. All patients were evaluated by the range of motion of the elbow and the Broberg-Morrey score. RESULTS: All fractures had healed without non-union, and the average time was 13.6 (range 8-17) weeks. The mean follow-up was 42.5 (range 24-80) months. The mean flexion was 117.1° (range 90°-135°), and the mean extension was 17.5° (range 0°-45°). The mean pronation was 74.4° (range 45°-85°), and the mean supination was 84.3° (range 60°-90°). The average Broberg-Morrey score was 86.2 (range 68-98) points with 10 excellent, 7 good and 3 fair results. CONCLUSION: K-wires, absorbable rods and sutures combined with hinged external fixator are feasible for fixation of capitellar and trochlear fractures. However, due to the absence of a control group (such as Herbert screw fixation), comparative studies are still needed to demonstrate the safety and reliability of K-wires for fixation.