Fibrous Scar Tissue Formation Research Articles

TSG6-Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model.

Intrauterine adhesion (IUA) is characterized by the formation of fibrous scar tissue within the uterine cavity, which significantly impacts female reproductive health and even leads to infertility. Unfortunately, severe cases of IUA currently lack effective treatments. This study presents a novel approach that utilizes tumor necrosis factor-(TNF) stimulated gene 6 (TSG6)-modified exosomes (Exos) in conjunction with an injectable thermosensitive hydrogel (CS/GP) to mitigate the occurrence of IUA by reducing endometrium fibrosis in a mouse IUA model. This study demonstrate that TSG6-modified Exos effectively inhibits the activation of inflammatory M1-like macrophages during the initial stages of inflammation and maintains the balance of macrophage phenotypes (M1/M2) during the repair phase. Moreover, TSG6 inhibits the interaction between macrophages and endometrial stromal fibroblasts, thereby preventing the activation of stromal fibroblasts into myofibroblasts. Furthermore, this research indicates that CS/GP facilitates the sustained release of TSG6-modified Exos, leading to a significant reduction in both the manifestations of IUA and the extent of endometrium fibrosis. Collectively, through the successful construction of CS/GP loaded with TSG6-modified Exos, a reduction in the occurrence and progression of IUA is achieved by mitigating endometrium fibrosis. Consequently, this approach holds promise for the treatment of IUA.

A Case of Myelopathy Due to Fibrous Scar Tissue Formation around the Lead of Spinal Cord Stimulation Placed in Cervical Portion

A Case of Myelopathy Due to Fibrous Scar Tissue Formation around the Lead of Spinal Cord Stimulation Placed in Cervical Portion

3D-Printed Auxetic Skin Scaffold for Decreasing Burn Wound Contractures at Joints.

For patients with severe burns that consist of contractures induced by fibrous scar tissue formation, a graft must adhere completely to the wound bed to enable wound healing and neovascularization. However, currently available grafts are insufficient for scar suppression owing to their nonuniform pressure distribution in the wound area. Therefore, considering the characteristics of human skin, which is omnidirectionally stretched via uniaxial stretching, we proposed an auxetic skin scaffold with a negative Poisson's ratio (NPR) for tight adherence to the skin scaffold on the wound bed site. Briefly, a skin scaffold with the NPR effect was fabricated by creating a fine pattern through 3D printing. Electrospun layers were also added to improve adhesion to the wound bed. Fabricated skin scaffolds displayed NPR characteristics (-0.5 to -0.1) based on pulling simulation and experiment. Finger bending motion tests verified the decreased marginal forces (<50%) and deformation (<60%) of the NPR scaffold. In addition, the filling of human dermal fibroblasts in most areas (>95%) of the scaffold comprising rarely dead cells and their spindle-shaped morphologies revealed the high cytocompatibility of the developed scaffold. Overall, the developed skin scaffold may help reduce wound strictures in the joints of patients with burns as it exerts less pressure on the wound margin.

Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice.

Poor tendon-bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon-bone integration, which may be ascribed to modulation of angiogenesis-osteogenesis crosstalk coupled by type H vessels.

Improved Muscle Regeneration into a Joint Prosthesis with Mechano-Growth Factor Loaded within Mesoporous Silica Combined with Carbon Nanotubes on a Porous Titanium Alloy.

Total joint replacement (TJR) is widely applied as a promising treatment for the reconstruction of serious joint diseases but is usually characterized by critical loss of skeletal muscle attachment to metal joint prostheses, resulting in fibrous scar tissue formation and subsequent motor dysfunction. Tissue engineering technology may provide a potential strategy for skeletal muscle regeneration into metal joint prostheses. Here, a porous titanium (Ti) alloy scaffold coated with carbon nanotubes (CNTs) and mesoporous silica nanoparticles (MSNs) through electrophoretic deposition (EPD) was designed as a mechano-growth factor (MGF) carrier. This two-layered coating exhibits a nanostructured topology, excellent MGF loading, and prolonged release performance via covalent bonding to improve myoblast adhesion, proliferation and myogenic differentiation in porous Ti alloy scaffolds without cytotoxicity. The Akt/mTOR signaling pathway plays a key role in this process. Furthermore, in vivo studies show that the scaffold promotes the growth of muscle, rather than fibrotic tissue, into the porous Ti alloy structure and improves muscle-derived mechanical properties, the migration of satellite cells, and possibly immunomodulation. In summary, this nanomaterial-coated scaffold provides a practical biomaterial platform to regenerate periprosthetic muscle tissue and restore comparable motor function to that of the natural joint.

Application of Stem Cell Therapy for ACL Graft Regeneration.

Graft regeneration after anterior cruciate ligament (ACL) reconstruction surgery is a complex three-stage process, which usually takes a long duration and often results in fibrous scar tissue formation that exerts a detrimental impact on the patients' prognosis. Hence, as a regeneration technique, stem cell transplantation has attracted increasing attention. Several different stem cell types have been utilized in animal experiments, and almost all of these have shown good capacity in improving tendon-bone regeneration. Various differentiation inducers have been widely applied together with stem cells to enhance specific lineage differentiation, such as recombinant gene transfection, growth factors, and biomaterials. Among the various different types of stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) have been investigated the most, while ligament stem progenitor cells (LDSCs) have demonstrated the best potential in generating tendon/ligament lineage cells. In the clinic, 4 relevant completed trials have been reported, but only one trial with BMSCs showed improved outcomes, while 5 relevant trials are still in progress. This review describes the process of ACL graft regeneration after implantation and summarizes the current application of stem cells from bench to bedside, as well as discusses future perspectives in this field.

Natural Biomineralization-Inspired Magnesium Silicate Composite Coating Upregulates Osteogenesis, Enabling Strong Anterior Cruciate Ligament Graft-Bone Healing In Vivo.

Artificial ligaments prepared from polyethylene terephthalate (PET) are widely accepted for clinical anterior cruciate ligament (ACL) reconstruction to recover the native function of knee joints. However, due to the chemical inertness and hydrophobicity of PET, improving its bioactivity and promoting graft-bone integration are still great challenges. Inspired by the natural biomineralization process on the surface of a historical stone, in this study, a bioactive organic/inorganic composite coating that is composed of poly(allylamine hydrochloride) and chondroitin sulfate with magnesium silicate (MgSiO3) doping is developed for surface modification of PET (MSPC-PET). This composite coating promotes adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs) and its bioactive inorganic components (MgSiO3) could induce osteogenic differentiation of BMSCs. Furthermore, an in vivo experiment indicated that this composite coating might afford superior graft-bone integration between MSPC-PET and the host bone tunnel, and fibrous scar tissue formation was also inhibited. More importantly, a biomechanical analysis proved that there was a strong integration between the MSPC-PET graft and the bone tunnel, which will improve biomechanical properties for the restoration of ACL function. This study shows that this bioactive composite coating-modified PET graft for the ACL reconstruction can effectively achieve good integration of ACL artificial grafts and bone tunnels and prevent surgical failure.

Fibrosis following Acute Skeletal Muscle Injury: Mitigation and Reversal Potential in the Clinic.

Skeletal muscle injuries occur often in athletics and in daily life. In minor injuries, muscles are able to regenerate completely and recover their functional capabilities. However, in the case of severe injuries, the injured muscle cannot recover to a functional level because of the formation of fibrous scar tissue. The physical barrier of scars is significantly challenged in both research and clinical treatment. Fibrous scar tissue not only limits cells' migration, but also contributes to normal tissue biomechanical properties. This scar formation creates an unsuitable environment for tissue structure resulting in frequent pain. Antifibrosis treatment is one of the major strategies used to augment muscle regeneration and accelerate its functional recovery. This review will discuss the currently available methods for improving muscle regeneration with a specific focus on antifibrosis applications. We also discussed several novel hypotheses and clinical applications in muscle fibrosis treatment currently in practice.

Effet de l’atélocollagène sur la cicatrisation des réparations de la racine méniscale médiale à l’aide du point Mason–Allen modifié

IntroductionAddition of collagen during medial meniscal root repair (MMRR) may improve meniscal root healing minimizing fibrous scar tissue formation. The purpose of this study was to verify the effect of atelocollagen on MMRR using the modified Mason–Allen stitch when compared with that of the conventional pull-out repair by assessing the clinical and radiological outcomes. HypothesisIt was hypothesized that atelocollagen would enhance the healing effect on the meniscal root following MMRR. Moreover, we presumed that MMRR with atelocollagen application might reduce meniscal extrusion by promoting healing. Materials and methodsA total of 47 patients who underwent MMRR using the modified Mason–Allen stitch between 2015 and 2016 were included, and they were divided into group A (atelocollagen application; n=25) and group R (MMRR without atelocollagen application; n=22). The postoperative clinical outcomes, radiological outcomes, and meniscal root healing and medial compartment cartilage status on follow-up magnetic resonance imaging (MRI) were compared between the two groups. ResultsMean follow-up duration was 26.4±4.8 months in group A and 27.1±5.2 months in group R (p=0.598). Mean duration from surgery to follow-up MRI was 12.5±1.4 months in group A and 12.7±1.2 months in group R (p=0.604). The subjective knee scores improved significantly in both groups at the last follow-up (all, p<0.001). The Kellgren–Lawrence (K-L) grade progressed in 16% and 22.7% in group A and group R, respectively (p=0.351). Follow-up MRI showed progression of cartilage loss in the medial compartment in 28% and 40.9% in group A and group R, respectively (p=0.355). In terms of meniscal root healing, 18 (72%) and 12 (54.5%) patients had complete healing, and 6 (24%) and 8 (36.4%) patients had partial healing in groups A and R, respectively. The mean value of the intrameniscal signal intensity (IMSI) of the meniscal root based on MRI in group A was significantly lower than that in group R (p<0.001). The medial meniscal extrusion in groups A and R decreased by 0.2±0.1mm and 0.1±0.3mm following MMRR without significant differences (p=0.056 and p=0.229, respectively). The IMSI presented significant negative correlations with the root healing status and significant positive correlations with K-L grade progression (p<0.05). DiscussionAtelocollagen application during MMRR yielded lower IMSIs, suggesting better healing, than did conventional pull-out root repair. However, this technique could not demonstrate beneficial effects on meniscal extrusion. Level of evidenceIII, retrospective case-control study.

Effect of atelocollagen on the healing status after medial meniscal root repair using the modified Mason–Allen stitch

IntroductionAddition of collagen during medial meniscal root repair (MMRR) may improve meniscal root healing minimising fibrous scar tissue formation. The purpose of this study was to verify the effect of atelocollagen on MMRR using the modified Mason–Allen stitch when compared with that of the conventional pullout repair by assessing the clinical and radiological outcomes. HypothesisIt was hypothesised that atelocollagen would enhance the healing effect on the meniscal root following MMRR. Moreover, we presumed that MMRR with atelocollagen application might reduce meniscal extrusion by promoting healing. Materials and methodsA total of 47 patients who underwent MMRR using the modified Mason–Allen stitch between 2015 and 2016 were included, and they were divided into group A (atelocollagen application; n=25) and group R (MMRR without atelocollagen application; n=22). The postoperative clinical outcomes, radiological outcomes, and meniscal root healing and medial compartment cartilage status on follow-up magnetic resonance imaging (MRI) were compared between the two groups. ResultsMean follow-up duration was 26.4±4.8 months in group A and 27.1±5.2 months in group R (p=0.598). Mean duration from surgery to follow-up MRI was 12.5±1.4 months in group A and 12.7±1.2 months in group R (p=0.604). The subjective knee scores improved significantly in both groups at the last follow-up (all, p<0.001). The Kellgren–Lawrence (K–L) grade progressed in 16% and 22.7% in group A and group R, respectively (p=0.351). Follow-up MRI showed progression of cartilage loss in the medial compartment in 28% and 40.9% in group A and group R, respectively (p=0.355). In terms of meniscal root healing, 18 (72%) and 12 (54.5%) patients had complete healing, and 6 (24%) and 8 (36.4%) patients had partial healing in groups A and R, respectively. The mean value of the intra-meniscal signal intensity (IMSI) of the meniscal root based on MRI in group A was significantly lower than that in group R (p<0.001). The medial meniscal extrusion in groups A and R decreased by 0.2±0.1mm and 0.1±0.3mm following MMRR without significant differences (p=0.056 and p=0.229, respectively). The IMSI presented significant negative correlations with the root healing status and significant positive correlations with K–L grade progression (p<0.05). DiscussionAtelocollagen application during MMRR yielded lower IMSIs, suggesting better healing, than did conventional pullout root repair. However, this technique could not demonstrate beneficial effects on meniscal extrusion. Level of evidenceIII, retrospective case-control study.

Systematic Review of Literature on the Efficiency of Using PRP in Arthroscopic Rotator Cuff Repair

Abstract Rotator cuff tears are one of the most common shoulder problems and the incidence of this condition is increasing along with an aging population. Despite satisfactory results for rotator cuff repair the quality and speed of healing remain problematic. Several studies have demonstrated that native tendon-bone insertions were not restored after tendon to bone repair. Healing of repaired tendons occurred via fibrous scar tissue formation rather than via the regeneration of a histologically normal insertion, and thus repaired tendons have inferior mechanical properties and are more susceptible to retear. Presumably, this is the most significant reason that account for tendon repair failure. Despite recent biomechanical advances in fixation, rates of retear are still high. Tendons consume little energy, and as a consequence healing is slow after injury. Increasing the speed of healing would allow earlier return to work, sport, and activities of daily living, which would be helpful for both the elite athlete and general public. Platelet rich plasma was first popularized in maxillofacial and plastic surgery, but now is thought to enhance and accelerate the repair and regeneration of a variety of tissues, such as bone, cartilage, tendon, ligament, and muscle. This systematic review reporting the effect of PRP after arthroscopic rotator cuff repair.

Accelerated Wound Healing by a Topical Wound Healing Lipogel in Patients Undergoing Catheter De-placement - Evidence from a Randomized, Controlled Clinical Study

Objective: The purpose of this clinical study was to assess a novel wound model and to compare the wound healing properties of a topical wound healing hydroactive lipogel (MediGel®) promoting moist wound environment versus standard treatment by a standard plaster und dry environmental conditions in patients undergoing catheter de-placement as a model for non-acute wounds affecting all skin layers in real life conditions (moist environment does improve granulation & epithelialization supported by Lipogel – the MEDIGEL trial). Methods: Patients (n=69) admitted to the dialysis ward of a tertiary care institution with acute or chronic renal insufficiency and in need for dialysis were enrolled into a prospective, observer-blind, randomized, controlled, inter-individual experimental comparison study. Patients enrolled were undergoing placement of Sheldon multi-lumen catheter (11 French diameter) in the external jugular vein at the neck by Seldinger technique to enable access for hemodialysis. One group of patients which had catheter displaced after one session of hemodialysis was regarded as acute wound group. A different group of patients had catheter withdrawn after 14 (+/- 2 days) and was classified as non-acute wound group. Topical treatments were randomly allocated, i.e. traditional care with standard plaster (control group) or investigational product (promoting moist environment) beneath a standard plaster (investigational product). Wound healing was assessed (digital photography, visual scoring) and analyzed via comparison of area under curve at day 0, 3 and 7 after displacement of catheter. Results: Evaluation showed significantly faster wound healing results for the investigational product in comparison to standard (all time points) and with significant AUC difference in both patient groups, acute and non-acute. Visible re-epithelialization was recorded from day 3 to day 7 in acute wounds, delayed in non-acute wounds. Standard plaster-treated wounds remained open and had markedly larger wound area. Formation of fibrous scar tissue was minimal but less prominent in patients treated with the hydroactive lipogel in the non-acute group due to faster epithelialization promoted by moist environment. Conclusion: Clinically relevant accelerated epithelialization and faster wound healing were observed for the investigational product compared to traditional treatment indicating superiority of moist wound environmental conditions both in acute and non-acute wounds after displacement of catheter placed into the jugular vein for 5 hours or 2 weeks in patients undergoing hemodialysis. The model is an innovative approach to study acute and non-acute wounds affecting all three skin layers and should be further investigated.

Native Enthesis Preservation Versus Removal in Rotator Cuff Repair in a Rabbit Model

The purpose of this study was to explore whether preservation of native enthesis during rotator cuff repair (RCR) results in a histologically and biomechanically better rotator cuff-greater tuberosity (RC-GT) connection in an animal model. Thirty-six New Zealand white rabbits were used in this study. The supraspinatus tendons were cut from the footprint to create a rotator cuff tear (RCT) on both shoulders, followed by immediate repair, with a 1mm thick tendon stump remaining on the footprint. On one side, RCR was performed by attaching the medial rotator cuff to the GT over the footprint stump layer (enthesis preservation [EP] approach). On the other side, the footprint stump and enthesis were fully removed and the footprint was decorticated. The repair was performed by attaching the medial rotator cuff onto the spongy bone surface in the footprint area (enthesis removal [ER] approach). Twelve rabbits were sacrificed at 4, 8, and 12weeks, of which 6 were used for histological analysis and 6 for biomechanical evaluation. Histological examination revealed that in the EP group, the native enthesis healed well with the reattached cuff tendon, and continuous collagen crossed the tendon-tendon interface area at 12weeks. However, in the ER group, there was only fibrous scar tissue formation at the tendon-bone interface. Biomechanical testing revealed a significantly higher load to failure (P= .001) of the RC-GT structure in the EP group than that in the ER group at 12weeks. For acute RCT with remnant enthesis, EP-RCR incorporates the native enthesis functionally in the restored RC-GT connection and enhances the RC-GT connection when compared with ER-RCR at 12weeks in a rabbit model. This finding justifies a human trial because in RCR with a remnant footprint, the EP technique may be adopted for a better RC-GT connection.

Application of arthroscopy in treatment of sports traumatic ankle arthritis

To introduce the methods and experience of arthroscopy treating different types of sports traumatic ankle arthritis.Methods The study involved 25 patents with spots traumatic ankle arthritis treated under ankle arthroscopy from January 2008 to October 2010.American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scoring system was applied to make functional evaluation before and after operation.Also,anterior drawer stress radiographs were used to assess the stability of joint.All patients had arthroscopic examination and received corresponding treatments,including synovial scar tissue resection,cartilage surface trimming,and microfracture management.Five patients underwent stage Ⅰ extramalleolus ligament repair.Results Arthroscopy showed simple synovitis in four patients,impingement syndrome developed from synovitis with fibrous scar tissue formation in 10,tibial or talus cartilage lesions in 11 and congestion of fresh injury of fibular end in four.A total of 23 cases were followed up for average 13.5 months (range,6-24 months).The ankle-hindfoot score was increased from preoperative (54.3 ± 6.2) points to (81.5 ± 7.9) points at 1 month,(82.9 ± 2.5) points at 3 months,( 83.1 + 2.1 ) points at 6 months and ( 83.5 ± 3.9 ) points at 12 months,with statistical differences ( t =13.01,20.58,21.10,19.11 respectively,P＜0.05).The anterior drawer stress radiographs showed that the anterior translation of talus improved from preoperative ( 15.2 ± 2.5 ) mm to postoperative (3.5 ± 0.2 ) mm,with statistical difference ( t =9.33,P ＜ 0.05 ).The anterior drawer test and talus tilt test were both negative for all patients.Concluslons Ankle arthroscopy is characterized by micro trauma and fast recovery.Symptomatic treatment under arthroscopy can obviously relieve the uncomfortable symptoms following sports traumatic ankle arthritis. Key words: Ankle joint; Arthroscopy; Sports traumatic ankle arthritis

The Effect of Platelet-Rich Fibrin Matrix on Rotator Cuff Healing in a Rat Model (SS-62)

Healing following a rotator cuff repair occurs via fibrous scar tissue formation that is structurally and biomechanically different from native tissue. Failure to recapitulate the normal morphology of the tendon-bone enthesis has been theorized to contribute to structural failure of repairs. Platelets have long been shown to play an instrumental role in the normal healing response via the local secretion of growth factors and recruitment of reparative cells. The use of autologous platelet-rich fibrin matrix (PRFM) provides a sustained vehicle of growth factor delivery to augment tendon-bone healing post-surgical repair.

Differential gene expression analysis in fracture callus of patients with regular and failed bone healing

ObjectiveAlthough several systemic and local factors are known to impair fracture healing, there is still no explanation, why some patients with sufficient fracture stability, showing none of the existing risk factors, still fail to heal normally. An investigation of local gene expression patterns in the fracture gap of patients with non-unions could decisively contribute to a better understanding of the pathophysiology of impaired fracture healing. For the first time, this study compares the expression of a large variety of osteogenic and chondrogenic genes in patients with regular and failed fracture healing. MethodsBetween March 2006 and May 2007, a total of 130 patients who were surgically treated at the Berufsgenossenschaftliche Unfallklink Ludwigshafen were screened for the study. Tissue samples of patients with normal and failed fracture healing were collected intraoperatively. Patients were divided into groups depending on the fracture date, and only patients with fractures two to four weeks old and patients with non-unions more than 9 months old were included in the final analysis. For the gene expression analysis, a customised cDNA array – containing 226 genes involved in osteo- and chondrogenesis – was used. ResultsIn the cDNA array analysis, the expression of eight genes was significantly elevated two-fold or more in the group with failed fracture healing relative to the normal controls. Conversely, no genes were found to be expressed at a higher level in the control group. The identified genes are supposed to be involved in extracellular matrix assembly, cytoskeletal structure, and differentiative and proliferative processes. ConclusionsThe differences in gene expression pattern indicate a change in the composition and structure of the extracellular matrix, and a possible turn in the healing programme towards fibrous scar tissue formation, leading to non-union.

Injury induces a change in the functional characteristics of cells recovered from equine tendon.

Injury initiates a repair process characterized by influx of fibroblasts and the rapid formation of fibrous scar tissue and subsequent tissue contraction. The response to injury and behavior of the different tendon fibroblast populations, however, has been poorly characterized. We hypothesized that the fibroblasts recovered from tendon with acute injury would exhibit different cell properties relating to adhesion, migration and tensegrity. To test this hypothesis we evaluated the ability of fibroblasts recovered from normal and injured equine superficial digital flexor tendons (SDFTs). The injured tendon-derived cells showed greater contraction of the collagen gel but poorer adhesion to pepsin-digested collagen, and migration over extracellular matrix proteins compared to normal SDFT-derived fibroblasts. Thus, the cells present within the tendon after injury display different behavior related to wound healing.

Xenopus Laevisas a Novel Model to Study Long Bone Critical-Size Defect Repair by Growth Factor-Mediated Regeneration

We used the tarsus of an adult Xenopus laevis frog as an in vivo load-bearing model to study the regeneration of critical-size defects (CSD) in long bones. We found the CSD for this bone to be about 35% of the tarsus length. To promote regeneration, we implanted biocompatible 1,6 hexanediol diacrylate scaffolds soaked with bone morphogenetic proteins-4 and vascular endothelial growth factors. In contrast to studies that use scaffolds as templates for bone formation, we used scaffolds as a growth factor delivery vehicle to promote cartilage-to-bone regeneration. Defects in control frogs were filled with scaffolds lacking growth factors. The limbs were harvested at a series of time points ranging from 3 weeks to 6 months after implantation and evaluated using micro-computed tomography and histology. In frogs treated with growth factor-loaded scaffolds, we observed a cartilage-to-bone regeneration in the skeletal defect. Five out of eight defects were completely filled with cartilage by 6 weeks. Blood vessels had invaded the cartilage, and bone was beginning to form in ossifying centers. By 3 months, these processes were well advanced, and extensive ossification was observed in 6-month samples. In contrast, the defects in control frogs showed only formation of fibrous scar tissue. This study demonstrates the utility of a Xenopus model system for tissue engineering research and that the normal in vivo mechanism of endochondral bone development and fracture repair can be mimicked in the repair of CSD with scaffolds used as growth factor delivery mechanisms.

Late onset cervical myelopathy secondary to fibrous scar tissue formation around the spinal cord stimulation electrode

Case report. To report the late onset of cervical myelopathy secondary to fibrous scar tissue formation around an epidural electrode implanted for spinal cord stimulation (SCS). Department of Orthopaedic Surgery, Hoshigaoka Koseinenkin Hospital, Osaka, Japan. A 49-year-old man who had an electrode implanted for SCS 5 years ago was referred to our department on 2 March 2005, complaining of difficulty using chopsticks and walking. A computed tomography scan with myelography revealed severe spinal cord compression around the epidural electrode. Surgical removal of the electrode was not effective. Removal of fibrous scar tissue during a second surgery significantly improved his neurological symptoms. Late onset cervical myelopathy secondary to fibrous scar tissue formation around the epidural electrode should be considered a possible event associated with SCS therapy.

Presurgical and Postsurgical Orthodontics in Patients With Cleft Lip and Palate

Patients with cleft lip and palate (CLP) usually have skeletal Class III malocclusion with maxillary deficiency due to the cleft itself and fibrous scar tissue formation caused by the reconstructive surgery. In adult CLP patients with excessive jaw discrepancies, orthognathic surgery is often indicated to correct their functional and esthetic problems. However, CLP patients have different inherent structures that may require a strategic approach compared with noncleft Class III patients. Main differences in skeletal and dental findings of lateral cephalograms between CLP and noncleft Class III surgical patients are to be demonstrated. Furthermore, a strategic approach with various mechanics in the presurgical orthodontic stage will be applied to suit the distinct characteristic of the case. Successful clinical outcome was critically dependent on the close communication among the related specialists.