Management of Laryngotracheal trauma: A review of current trends and future Directions.

Laryngotracheal trauma is rare but can pose serious threats to one's life. Presenting symptoms vary according to the severity of injury. Immediate Airway control is first step in the management, intubation should be considered by a senior member of the trauma team if the injury is minor while tracheostomy should be reserved for more severe injuries. Evaluation by a fibre-optic laryngoscopy and CT scan should be done whenever possible. Reconstruction is done according to the site involved using suture, titanium miniplates and stents. Tissue engineering has added a new horizon in this management but up till now complete laryngotracheal regeneration is very far-fetched, but tissue regeneration at individual sites have shown some positive results. More work needs to be done in this less explored field including laryngeal transplantation.

The combination of microfracture with induction of Wnt / ß- Catenin pathway, leads to enhanced cartilage regeneration.

INTRODUCTION: Microfracture does not lead to complete healing of full-thickness cartilage defects. The aim of this study was to evaluate the effect of modifying Wnt/ß-catenin signaling following microfracture, on the restoration of a full-thickness cartilage defect in a rabbit model. The modification of the canonical Wnt pathway was achieved through per os administration of lithium carbonate, which is an intracellular inhibitor of glycogen synthase kinase 3-ß (Gsk3-ß) and therefore induces Wnt/ß-catenin signaling. MATERIALS AND METHODS: Full-thickness cartilage defects of 4 mm in diameter were created in the patellar groove of the right femurs of 18 male New Zealand white rabbits. The rabbits were divided into three groups of six (n = 6) based on post-surgery treatment differences, as follows: microfracture only (group 1), microfracture plus lithium carbonate 7 mM in the drinking water for 1 week (group 2), microfracture plus lithium carbonate 7 mM in the drinking water for 4 weeks (group 3). All animals were sacrificed 9 weeks after surgery. The outcome was assessed histologically, by using the International Cartilage Repair Society (ICRS) visual histological scale. Immunohistochemistry for type II collagen was also conducted. RESULTS: Statistical analysis of the histological ICRS scores showed that group 3 was significantly superior to group 1 in four out of six ICRS categories, while group 2 was superior to 1 in only two out of six. CONCLUSION: The combination of microfracture and systematic administration of lithium carbonate 7 mM for 4 weeks shows statistically significant superiority in four out of six ICRS categories compared with microfracture only for the treatment of full-thickness cartilage defects in a rabbit experimental model.

Trypsin Pre-Treatment Combined With Growth Factor Functionalized Self-Assembling Peptide Hydrogel Improves Cartilage Repair in Rabbit Model.

The objective of this study was to improve cartilage repair and integration using self-assembling KLD hydrogel functionalized with platelet-derived growth factor-BB and heparin-binding insulin-like growth factor-1 with associated enzymatic trypsin pre-treatment of the native cartilage. Bilateral osteochondral defects were created at the central portion of the femoral trochlear groove of 48 skeletally mature, white New Zealand rabbits. One limb received a randomly assigned treatment and the contralateral limb served as the control. Treated defects were exposed to trypsin for 2 min and filled with self-assembling KLD hydrogel only, or associated to growth factors. All control limbs received KLD hydrogel alone or received only trypsin but not hydrogel. Ninety days post-defect creation, the rabbits were euthanized and magnetic resonance imaging, radiography, macroscopic evaluation, histology, and immunohistochemistry of the joint and repaired tissue were performed. Mixed model analyses of variance were utilized to assess the outcome parameters and individual comparisons were performed using Least Square Means procedure and differences with p-value < 0.05 were considered significant. Trypsin enzymatic pre-treatment improved cellular morphology, cluster formation and subchondral bone reconstitution. Platelet-derived growth factor-BB improved subchondral bone healing and basal integration. Heparin-binding insulin-like growth factor-1 associated with platelet-derived growth factor improved tissue and cell morphology. The authors conclude that self-assembling KLD hydrogel functionalized with platelet-derived growth factor and heparin-binding insulin-like growth factor-1 with associated enzymatic pre-treatment of the native cartilage with trypsin resulted in an improvement on the cartilage repair process. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2307-2315, 2019.

Plasma rico en plaquetas: ¿mito o realidad? / Platelet-rich plasma: myth or reality?

El plasma rico en plaquetas (PRP) es un preparado con fines terapéuticos cada vez más aceptado en diversas patologías musculoesqueléticas, debido a su teórico potencial para reparar tejidos con baja capacidad curativa. Se han realizado diversos ensayos clínicos aleatorizados que investigan la capacidad del PRP para la reparación de tendones, ligamentos, músculos y cartílago. Hasta la fecha existe evidencia 1A que apoya su uso para la epicondilitis lateral, la osteoartritis de rodilla, la fascitis plantar y tendinopatías del manguito rotador, y evidencia 1B en la tendinopatía del tendón rotuliano y la osteoartritis de cadera. Estudios retrospectivos, de cohortes y series de casos describen resultados prometedores del PRP para el tratamiento de otras patologías musculoesqueléticas. Al ser sus efectos secundarios menores que los de los grupos controles hacen que sea un tratamiento considerado como prácticamente inocuo y cada vez más usado. Son necesarios nuevos ensayos clínicos aleatorizados para establecer futuras indicaciones y confirmar su efectividad y seguridad

Platelet-rich plasma (PRP) is a preparation for therapeutic purposes that is increasingly accepted for various musculoskeletal disorders, due to its theoretical potential to repair tissues with poor healing capacity. Several randomised clinical trials have investigated the capacity of PRP to repair tendons, ligaments, muscles and cartilage, and to date there is level 1a evidence to support its use for lateral epicondylitis, osteoarthritis of the knee, plantar fasciitis and rotator cuff tendinopathy; and level 1b for patellar tendinopathy and osteoarthritis of the hip. Retrospective cohort studies and case series describe promising results with PRP for treating other musculoskeletal disorders. Since its side effects are fewer than those of the control groups, the treatment is considered practically harmless and is being increasingly used. Further randomised clinical trials are necessary to establish future indications, and to confirm effectiveness and safety

In situ repair of bone and cartilage defects using 3D scanning and 3D printing.

Three-dimensional (3D) printing is a rapidly emerging technology that promises to transform tissue engineering into a commercially successful biomedical industry. However, the use of robotic bioprinters alone is not sufficient for disease treatment. This study aimed to report the combined application of 3D scanning and 3D printing for treating bone and cartilage defects. Three different kinds of defect models were created to mimic three orthopedic diseases: large segmental defects of long bones, free-form fracture of femoral condyle, and International Cartilage Repair Society grade IV chondral lesion. Feasibility of in situ 3D bioprinting for these diseases was explored. The 3D digital models of samples with defects and corresponding healthy parts were obtained using high-resolution 3D scanning. The Boolean operation was used to achieve the shape of the defects, and then the target geometries were imported in a 3D bioprinter. Two kinds of photopolymerized hydrogels were synthesized as bioinks. Finally, the defects of bone and cartilage were restored perfectly in situ using 3D bioprinting. The results of this study suggested that 3D scanning and 3D bioprinting could provide another strategy for tissue engineering and regenerative medicine.

Microfracture combined with functional pig peritoneum-derived acellular matrix for cartilage repair in rabbit models.

Due to avascular and hypocellular nature of cartilage, repair of articular cartilage defects within synovial joints still poses a significant clinical challenge. To promote neocartilage properties, we established a functional scaffold named APM-E7 by conjugating a bone marrow-derived mesenchymal stem cell (BM-MSC) affinity peptide (E7) onto the acellular peritoneum matrix (APM). During in vitro culture, the APM-E7 scaffold can support better proliferation as well as better differentiation into chondrocytes of BM-MSCs. After implanting into cartilage defects in rabbits for 24weeks, compared with microfracture and APM groups, the APM-E7 scaffolds exhibited superior quality of neocartilage without transplant rejection, according to general observations, histological assessment, synovial fluid analysis, magnetic resonance imaging (MRI) and nanomechanical properties. This APM-E7 scaffold provided a scaffold for cell attachment, which was crucial for cartilage regeneration. Overall, the APM-E7 is a promising biomaterial with low immunogenicity for one-step cartilage repair by promoting autologous connective tissue progenitor (CTP) attachment. STATEMENT OF SIGNIFICANCE: We report the one-step transplantation of functional acellular peritoneum matrix (APM-E7) with specific mesenchymal stem cell recruitment to repair rabbit cartilage injury. The experimental results illustrated that the APM-E7 scaffold was successfully fabricated, which could specifically recruit MSCs and fill the cartilage defects in the femoral trochlear of rabbits at 24weeks post-surgery. The repaired tissue was hyaline cartilage, which exhibited ideal mechanical stability. The APM-E7 biomaterial could provide scaffold for MSCs and improve cell homing, which are two key factors required for cartilage tissue engineering, thereby providing new insights into cartilage tissue engineering.

Cost-effectiveness of Early Surgery versus Conservative Treatment with Optional Delayed Meniscectomy for Patients over 45†years with non-obstructive meniscal tears (ESCAPE study): protocol of a randomised controlled trial.

INTRODUCTION: Recent studies show similar outcome between surgery and conservative treatment in patients with non-obstructive meniscal tears. However, surgery is still often preferred over conservative treatment. When conservative treatment is non-inferior to surgery, shifting the current standard treatment choice to conservative treatment alone could save over €30 millions of direct medical costs on an annual basis. Economic evaluation studies comparing surgery to conservative treatment are lacking. METHODS AND ANALYSIS: A multicentre randomised controlled trial (RCT) with an economic evaluation alongside was performed to assess the (cost)-effectiveness of surgery and conservative treatment for meniscal tears. We will include 402 participants between 45 and 70 years with an MRI-confirmed symptomatic, non-obstructive meniscal tears to prove non-inferiority of conservative treatment. Block randomisation will be web-based. The primary outcome measure is a physical function, measured by the International Knee Documentation Committee 'Subjective Knee Form'. Furthermore, we will perform a cost-effectiveness and cost-utility analysis from societal perspective and a budget impact analysis from a societal, government and insurer perspective. Secondary outcomes include general health, quality of life, activity level, knee pain, physical examination, progression of osteoarthritis and the occurrence of adverse events. ETHICS AND DISSEMINATION: This RCT will be performed in accordance with the Declaration of Helsinki and has been approved by the Ethics Committee (number NL44188.100.13). The results of this study will be reported in peer-reviewed journals and at international conferences. We further aim to disseminate our results to guideline committees. TRIAL REGISTRATION NUMBER: NCT01850719.

Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury.

Cartilage tissue engineering is the hotspot of cartilage repair. The allogenic chondrocytes appear to be a promising source of seed cells in cartilage tissue engineering. In this study, we aimed to transplant allogenic chondrocytes with chitosan hydrogel (CS)-demineralized bone matrix (DBM) hybrid scaffold (CS/DBM) to repair rabbit cartilage injury with one-step operation. After the CS/DBM scaffold was successfully fabricated, it showed that the porous CS filled the large pores of DBM, which improved the distribution of seed cells in the CS/DBM scaffold. The allogenic chondrocytes at second passage were transplanted with different scaffolds to repair rabbit cartilage injury. Twenty-four weeks after surgery, the cartilage defect in the CS/DBM group was successfully filled as shown by MRI. Moreover, the histological score of CS/DBM group was significantly higher than that of the other groups. On the aspect of biomechanical property, the regenerated cartilage in the CS/DBM group were superior to those in the other groups as determined by nanoindentation. Meanwhile, no obvious inflammatory response was observed after the transplantation of allogenic chondrocytes at 24 weeks post-surgery. Furtherly, gene expression profile for cells within the repair tissue was compared with the allogenic chondrocytes before transplantation using Agilent microarray and RT-qPCR. The results showed that some genes beneficial to cartilage regeneration, such as BMP-7, HGF, and IGF-1, were upregulated one month after transplantation. Consequently, our study demonstrated that the transplantation of allogenic chondrocytes with CS/DBM scaffold successfully repaired rabbit cartilage injury with only one-step operation, thereby providing new insights into cartilage tissue engineering.

Delayed gadolinium-enhanced MRI of cartilage and T2 mapping for evaluation of reparative cartilage-like tissue after autologous chondrocyte implantation associated with Atelocollagen-based scaffold in the knee.

OBJECTIVE: To elucidate the quality of tissue-engineered cartilage after an autologous chondrocyte implantation (ACI) technique with Atelocollagen gel as a scaffold in the knee in the short- to midterm postoperatively, we assessed delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and T2 mapping and clarified the relationship between T1 and T2 values and clinical results. MATERIALS AND METHODS: In this cross-sectional study, T1 and T2 mapping were performed on 11 knees of 8 patients (mean age at ACI, 37.2 years) with a 3.0-T MRI scanner. T1implant and T2implant values were compared with those of the control cartilage region (T1control and T2control). Lysholm scores were also assessed for clinical evaluation. The relationships between the T1 and T2 values and the clinical Lysholm score were also assessed. RESULTS: There were no significant differences in the T1 values between the T1implant (386.64 ± 101.78 ms) and T1control (375.82 ± 62.89 ms) at the final follow-up. The implants showed significantly longer T2 values compared to the control cartilage (53.83 ± 13.89 vs. 38.21 ± 4.43 ms). The postoperative Lysholm scores were significantly higher than the preoperative scores. A significant correlation was observed between T1implant and clinical outcomes, but not between T2implant and clinical outcomes. CONCLUSION: Third-generation ACI implants might have obtained an almost equivalent glycosaminoglycan concentration compared to the normal cartilage, but they had lower collagen density at least 3 years after transplantation. The T1implant value, but not the T2 value, might be a predictor of clinical outcome after ACI.

Articular Cartilage Injury and Potential Remedies.

Osteoarthritis affects millions of people worldwide, is associated with joint stiffness and pain, and often causes significant disability and loss of productivity. Osteoarthritis is believed to occur as a result of ordinary "wear and tear" on joints during the course of normal activities of daily living. Posttraumatic osteoarthritis is a particular subset of osteoarthritis that occurs after a joint injury. Developing clinically relevant animal models will allow investigators to delineate the causes of posttraumatic osteoarthritis and develop means to slow or prevent its development after joint injury. Chondroprotectant compounds, which attack the degenerative pathways at a variety of steps, are being developed in an effort to prevent posttraumatic osteoarthritis and offer great promise. Often times, cartilage degradation after joint injury occurs despite our best efforts. When this happens, there are several evolving techniques that offer at least short-term relief from the effects of posttraumatic osteoarthritis. Occasionally, these traumatic lesions are so large that dramatic steps must be taken in an attempt to restore articular congruity and joint stability. Fresh osteochondral allografts have been used in these settings and offer the possibility of joint preservation. For patients presenting with neglected displaced intra-articular fractures that have healed, intra-articular osteotomy techniques are being developed in an effort to restore joint congruity and function. This article reviews the results of a newly developed animal model of posttraumatic osteoarthritis, several promising chondroprotectant compounds, and also cartilage techniques that are used when degenerative cartilage lesions develop after joint injury.

Hip Pain in Athletes - When It is Not the Labrum.

Hip pain is a relatively common complaint in sports. It is tempting to blame the athlete's symptoms on labral pathology. However, there is a high incidence of asymptomatic labral disease. Therefore, even when a labral tear is present, it may not be the underlying cause of the patient's pain. Clinicians should familiarize themselves with the large differential diagnosis for hip and pelvis pain to include nonmusculoskeletal pathology. This article reviews nonlabral causes of hip pain in athletes. For ease of classification, the hip is divided into anterior, lateral, and posterior regions.

Fibrous Scaffolds with Varied Fiber Chemistry and Growth Factor Delivery Promote Repair in a Porcine Cartilage Defect Model.

Current clinically approved methods for cartilage repair are generally based on either endogenous cell recruitment (e.g., microfracture) or chondrocyte delivery (e.g., autologous chondrocyte implantation). However, both methods culminate in repair tissue with inferior mechanical properties and the addition of biomaterials to these clinical interventions may improve their efficacy. To this end, the objective of this study was to investigate the ability of multipolymer acellular fibrous scaffolds to improve cartilage repair when combined with microfracture in a large animal (i.e., minipig) model. Composite scaffolds were formulated from a combination of hyaluronic acid (HA) fibers and poly(ɛ-caprolactone) (PCL) fibers, either with or without transforming growth factor-ß3 (TGFß3). After 12 weeks in vivo, material choice and TGFß3 delivery had a significant impact on outcomes; specifically, PCL scaffolds without TGFß3 had inferior gross appearance and reduced mechanical properties, whereas HA scaffolds that released TGFß3 resulted in improved histological scores and increased type 2 collagen content. Importantly, analysis of the overall dataset revealed that histology, but not gross appearance, was a better predictor of mechanical properties. This study highlights the importance of scaffold properties on in vivo cartilage repair as well as the need for numerous quantitative outcome measures to fully evaluate treatment methods.

Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) Based Electrospun 3D Scaffolds for Delivery of Autogeneic Chondrocytes and Adipose-Derived Stem Cells: Evaluation of Cartilage Defects in Rabbit.

The management of chondral defects has long been a challenge because of the poor self-healing capacity of articular cartilage. Many approaches ranging from symptomatic treatment to structural cartilage regeneration have obtained very limited satisfactory results. Cartilage tissue engineering, which involves an optimized combination of novel scaffolds, cell sources and growth factors, has emerged as a promising strategy for cartilage regeneration and repair. In this study, the cellular morphologies and the adhesion, migration and proliferation capabilities of adipose-derived stem cells (ASCs) and chondrocytes seeded on 3D scaffolds composed of electrospun poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB4HB) were evaluated. Next, TGF-ß1/scaffolds with 4:1 co-culture of ASCs and chondrocytes were implanted into the full thickness cartilage defects in rabbit knee for 16 weeks. ASCs and chondrocytes seeded on the scaffolds showed better adhesion, migration and proliferation than that on petri dishes in vitro. Importantly, implantation with TGF-ß1/scaffolds with delivery of ASCs and chondrocytes revealed desirable in vivo healing outcomes. These results demonstrate that ASCs have great potential in the field of tissue engineering. It is possible that the improvement in ASC-seeded electrospun 3D P3HB4HB scaffolds may ultimately lead to improved repair of cartilage injuries.

[Stem cells in orthopaedics]. / Kmenové bunky v ortopedii.

Sharing new ideas and approaches is needed to advance basic scientific research as well as the clinical application of stem cells. In this newsletter we present the current knowledge in stem cell research and therapy within the field of orthopaedics, presenting the definitions, types and sources of the stem cells. The second part of this newsletter focuses on the clinical application of stem cells in the therapy of tissues with very limited capacity for self-regeneration; this includes tendons and ligaments, particularly found in rotator cuff rupture. The sever problems associated with articular cartilage repair have lead to the need for the development of clinical research, with the aim of finding efficient clinical applications of stem cell therapy in cartilage defects and osteoarthritis. However in addition to this, such therapy could be used for the regeneration of bone, as in bone defect repair. The clinical outcome of stem cell therapy is a promising option for the treatment of cartilage, bone and tendon defects; however an increased sample size and additional long-term prospective randomised studies are needed to confirm these preliminary results.

Effect of microfracture and autologous-conditioned plasma application in the focal full-thickness chondral defect of the knee: an experimental study on rabbits.

PURPOSE: The aim of the present study was to evaluate the effect of microfracture and intraarticular autologous conditioned plasma (ACP) injection on cartilage regeneration in a focal full-thickness chondral defect model created in the knee joint. METHODS: Full-thickness chondral defects of 3 × 6 mm(2) were surgically created in right medial femoral condyles (MFC) of New Zealand rabbits, and the rabbits were then divided into three groups according to treatment: Group 1 received only microfracture (mfx), Group 2 received mfx plus intraarticular ACP, and Group 3 received mfx; the defect was covered by the periosteum, and then, ACP was applied subperiosteally and intraarticularly. Twelve weeks after injection, the animals were sacrificed and the femoral condyles were evaluated macroscopically and histologically by hematoxylin-eosin staining. Then, histological sections were scored using the International Cartilage Repair Society (ICRS) visual histological scale. RESULTS: Findings showed that in both mfx/ACP-treated groups, the defects were filled regularly and smoothly, the defects had a greater fill and good integration into the surrounding host tissue, and the repair matrix had more hyaline-like character. On the other hand, defects were filled with an irregular, fibrous cartilage in the mfx-treated group. Histological scores in Group 2 and Group 3 were better compared to Group 1. CONCLUSION: In the present study, we were able to demonstrate a beneficial effect of intraarticular administration of ACP as a coadjuvant of microfractures in order to regenerate hyaline-like cartilage in full-thickness chondral lesions in a rabbit model.

Cartilage immunoprivilege depends on donor source and lesion location.

The ability to repair damaged cartilage is a major goal of musculoskeletal tissue engineering. Allogeneic (same species, different individual) or xenogeneic (different species) sources can provide an attractive source of chondrocytes for cartilage tissue engineering, since autologous (same individual) cells are scarce. Immune rejection of non-autologous hyaline articular cartilage has seldom been considered due to the popular notion of "cartilage immunoprivilege". The objective of this study was to determine the suitability of allogeneic and xenogeneic engineered neocartilage tissue for cartilage repair. To address this, scaffold-free tissue engineered articular cartilage of syngeneic (same genetic background), allogeneic, and xenogeneic origin were implanted into two different locations of the rabbit knee (n=3 per group/location). Xenogeneic engineered cartilage and control xenogeneic chondral explants provoked profound innate inflammatory and adaptive cellular responses, regardless of transplant location. Cytological quantification of immune cells showed that, while allogeneic neocartilage elicited an immune response in the patella, negligible responses were observed when implanted into the trochlea; instead the responses were comparable to microfracture-treated empty defect controls. Allogeneic neocartilage survived within the trochlea implant site and demonstrated graft integration into the underlying bone. In conclusion, the knee joint cartilage does not represent an immune privileged site, strongly rejecting xenogeneic but not allogeneic chondrocytes in a location-dependent fashion. This difference in location-dependent survival of allogeneic tissue may be associated with proximity to the synovium. STATEMENT OF SIGNIFICANCE: Through a series of in vivo studies this research demonstrates that articular cartilage is not fully immunoprivileged. In addition, we now show that anatomical location of the defect, even within the same joint compartment, strongly influences the degree of the resultant immune response. This is one of the first investigations to show that (1) immune tolerance to allogeneic tissue engineered cartilage and (2) subsequent implant survival are dependent on the implant location and proximity to the synovium.

Application of pulsed electromagnetic fields after microfractures to the knee: a mid-term study.

PURPOSE: Pulsed electromagnetic fields (PEMFs) may improve clinical outcomes following microfractures and prevent their decline over time. METHODS: Sixty-eight patients who underwent partial medial meniscectomy and microfractures to the medial femoral condyle for management of grade III-IV cartilage lesions were randomly divided into two groups using a block randomization procedure. After surgery, 34 patients underwent PEMFs application in the I-ONE group; 34 patients underwent placebo treatment in the placebo group. All patients had the same postoperative rehabilitation protocol. Sixty patients (28 in the I-ONE group, 32 in the placebo group) were assessed at an intermediate follow-up of two years and a minimum follow-up of five years after surgery. RESULTS: The two groups were homogeneous. There was a significant improvement from baseline to the last minimum follow up of two years. At two years, IKDC and Lysholm and Constant scores were significantly improved compared to baseline in both groups with no significant inter-group differences. At the last follow up (minimum five years), clinical and functional outcomes were decreased in both the groups, with significant better outcomes in the I-ONE group. At five years, the percentage of patients still active at the same level they were pre-operatively was greater in the I-ONE group (82% vs 68%, P = 0.28). At radiographic assessment, at the latest evaluation, six patients (21.4%) in the I-ONE group and nine (28.1%) in the placebo group demonstrated grade I-II degenerative changes according to Fairbank grading system (Χ = 0.36, P = 0.55). CONCLUSIONS: PEMFs application can improve the effectiveness of microfracture in the long term.

Photocrosslinked layered gelatin-chitosan hydrogel with graded compositions for osteochondral defect repair.

A layered gelatin-chitosan hydrogel with graded composition was prepared via photocrosslinking to simulate the polysaccharide/collagen composition of the natural tissue and mimic the multi-layered gradient structure of the cartilage-bone interface tissue. Firstly, gelatin and carboxymethyl chitosan were reacted with glycidyl methacrylate (GMA) to obtain methacrylated gelatin (Gtn-GMA) and carboxymethyl chitosan (CS-GMA). Then, the mixed solutions of Gtn-GMA in different methacrylation degrees with CS-GMA were prepared to form the superficial, transitional and deep layers of the hydrogel, respectively under the irradiation of ultraviolet light, while polyhedral oligomeric silsesquioxane was introduced in the deep layer to improve the mechanical properties. Results suggested that the pore sizes of the superficial, transitional and deep layers of the layered hydrogel were 115 ± 30, 94 ± 34, 51 ± 12 µm, respectively and their porosities were all higher than 80 %. The compressive strengths of them were 165 ± 54, 565 ± 50 and 993 ± 108 kPa, respectively and the strain of the gradient hydrogel decreased along the thickness direction, similar to the natural tissue. The in vitro cytotoxicity results showed that the hydrogel had good cytocompatibility and the in vivo repair results of osteochondral defect demonstrated remarkable recovery by using the gradient gelatin-chitosan hydrogel, especially when the hydrogel loading transforming growth factor-ß1. Therefore, it was suggested that the prepared layered gelatin-chitosan hydrogel in this study could be potentially used to promote cartilage-bone interface tissue repair.

[Clinical relevance of unloading in cartilage therapy of the knee--shoe insoles, knee braces or additional operative procedure?]. / Druckentlastung (Unloading) im Kniegelenk in Kombination mit knorpelchirurgischen Eingriffen.

Restoration of a neutral biomechanical environment and reduction of overload is an important factor contributing to the success of any cartilage repair procedure. Reduction of overload can by achieved by so called unloading procedures in order to reduce intraarticular pressure from the repair zone. Unloading can be achieved via loss of weight, wedged shoe insoles, knee braces or via operations such as osteotomies around the knee joint. The cartilage therapy and the concomitant unloading procedure should be adapted to the individual pathology and realistic aims of the patient. Wedged insoles and braces are the least invasive treatment methods. In comparison, however, beneficial effects of braces outline those of laterally wedged heels. Nevertheless long-term compliance with insoles and braces is poor. Concerning braces either because the positive effects of the braces are too small or because the adverse effects are too large. Unloading in the long run may only be achieved through operative procedures. When an osteotomy seems to be too invasive the arthroscopic release of the posterior oblique ligament might be an option. Patients with an intact contralateral chondral status, medium to slight malalignment who want to remain at high activity levels, remain good candidates for unloading osteotomies.