Subchondral Defects Research Articles

Subchondroplasty® (SCP) Provides Resolution of Symptoms and Functional Improvements in Mild-to-Moderate Knee Osteoarthritis with Persistent Bone Marrow Lesions: 12-Month Follow-Up Results from a Multicentric Open-Label Prospective Clinical Trial.

Introduction. Bone marrow lesions (BMLs) are MRI-visible subchondral bone alterations, highly correlated with symptoms in the knee. Subchondroplasty (SCP) is able to fill the subchondral defects associated with BMLs using an injectable bone substitute material. The aim of the present study is to evaluate the 12-month outcomes of the SCP in the treatment of symptoms of mild-to-moderate knee osteoarthritis (OA) patients with persistent BMLs of the knee. Materials and Methods. Subjects affected by BMLs of the femoral condyle or tibial plateau that were present for >3 months and not responsive to conservative treatments were enrolled in this prospective multicenter trial. All the patients underwent SCP. Follow-up was conducted at 1, 3, 6 and 12 months. All subjects completed Numerical Rating Scale (NRS) for pain, Knee Injury and Osteoarthritis Outcome (KOOS) score, Euro Quality of life-5 dimensions (EQ-5D) score, and a subject global satisfaction scale. Demographic information of the patients was also collected. Results. A total of 79 patients completed the 12-month follow-up. Statistically significant improvements on all clinical scales were registered from baseline to the 12-month follow-up. No severe adverse events were reported. Four patients were considered failed. A 12-month subgroup analysis was performed to evaluate the possible correlation between all the KOOS subscales and age, gender, number of BMLs, location of BMLs, and Kellgren-Lawrence grade: no statistically significant associations were observed. Conclusion. SCP is a safe and effective procedure for the treatment of symptoms related to persisting BMLs in mild-to-moderate osteoarthritic knees, with a low failure rate up to 12 months' evaluation.

Low-field magnetic resonance imaging of sagittal groove disease of the proximal phalanx in non-racing sport horses.

Injuries of the sagittal groove of the proximal phalanx (P1) in equine athletes are considered to predominantly occur due to chronic bone stress overload. To describe the range of abnormalities that is present in the sagittal groove in a large group of horses diagnosed with sagittal groove disease (SGD) on low-field MRI. Retrospective, cross-sectional. Medical records were searched to identify initial MRI images of horses diagnosed with SGD and these were blindly evaluated using a semi-quantitative grading scheme and novel SGD MRI classification system reflecting potential pathways of pathological progression and severity of stress injury. A total of 132 limbs from 111 horses were included in the study; predominantly warmbloods competing in showjumping (n = 83) and dressage (n = 18). SGD MRI classifications were: 0 (normal, n = 0), 1 (small subchondral defect, n = 2), 2 (osseous densification, n = 28), 3 (subchondral microfissure with osseous densification, n = 7), 4 (bone oedema-like signal within the subchondral ± trabecular bone and ± subchondral microfissure or demineralisation, n = 72), 5 (incomplete macrofissure/fracture, n = 23) and 6 (complete fracture, n = 0). Classification 4c (bone oedema-like signal with demineralisation) and 5 had higher proportions in the plantar third of hindlimbs (3% and 10%, respectively) compared with forelimbs (0% and 0%, respectively). SGD classification and extent of bone oedema-like signal were not significantly different between lame (n = 116) and non-lame limbs (n = 16) (both p > 0.05). Periosteal new bone and oedema-like signal were identified (either confidently or suspected) at the dorsoproximal aspect of P1 in 25% and 39% of limbs, respectively. Inclusion via diagnoses in original MRI reports, variable clinical history, small size of some classification groups. The presence or absence of lameness is not a dependable measure of the severity of SGD. The periosteal oedema-like signal of P1 has not previously been described in MRI of SGD and further supports the concept of bone stress injury.

Management of Traumatic Bone Defects in Tibial Plateau Fractures with Antibiotic-Impregnated Biodegradable Calcium Sulfate Beads: A Prospective Clinical Trial

Objectives: The purpose of this study was to assess adverse events and resorption of antibiotic-impregnated calcium sulfate beads used as a nonstructural void filler in tibia plateau fractures. This device may be more adaptable to a specific bacterium than vancomycin powder as it allows the mixtures of specific bactericidal antibiotics to treat bacterium with specific sensitivities. Design: A multicenter, non-randomized, uncontrolled prospective cohort study. Setting: Five level 1 trauma centers. Participants: Thirty adults with an acute closed tibia plateau fracture, OTA 41B and 41C fractures, requiring operative fixation. Intervention: After fracture fixation, the subchondral bone void was filled with the study device. Main Outcome Measures: Local wound reaction to the device was assessed and resorption of the calcium sulfate was measured on serial x-rays. Follow-up assessments occurred at six weeks, three months, six months and one year, with a CT scan performed at six months to determine resorption of the device. Results: Thirteen male and 17 female participants were recruited with a mean age of 53.3 ± 12.8 years. The median age was 55 years with a range of 29 to 78 years of age. Two participants reported serous drainage: one resolved without treatment, the other was diagnosed as a deep infection and required plate removal and oral antibiotics. There were no local or systemic allergic reactions. Resorption of the material averaged 70% by three months, 87% at six months, and 100% at one year. Conclusions: This device performed as anticipated and completely resorbed without any unexpected adverse events. It allowed for personalizing antibiotic choice with better reported elutional characteristics than vancomycin powder over two weeks and six weeks. Surgical site drainage was low, and 97% union rate was achieved. This is a safe surgical augment for local release of a chosen antibiotic into a contained subchondral defect in a periarticular fracture.

Effectiveness of Bilayer Scaffold Containing Chitosan/Gelatin/Diclofenac and Bovine Hydroxyapatite on Cartilage/Subchondral Regeneration in Rabbit Joint Defect Models.

Subchondral defects are often caused by trauma involving cartilage damage, leading to subsequent damage to the underlying bone, specifically the subchondral region. Bilayer scaffolds made from biomaterials, such as bovine hydroxyapatite, possess biocompatible and biodegradable properties that mimic the natural environmental conditions of target tissues so that they can support the formation of new tissues. On the other side, diclofenac as an anti-inflammatory drug potentiates to inhibit the inflammatory excess regarding the damage. This study aims to study the effectiveness of diclofenac scaffold to rabbit joint defect model. The scaffold was implanted in the rabbit femoral trochlear bone hole, which had a diameter of 5 mm and a depth of 4 mm. After 28 days of intervention, the animals were examined using macroscopic evaluation, hematoxylin-eosin (HE) staining, and immunohistochemistry (IHC) for type I collagen and type II collagen. Subsequently, the cartilage was evaluated using the International Cartilage Repair Society (ICRS) scoring system. The macroscopic ICRS scores were significantly higher (p < 0.05) in the bilayer scaffold implantation group compared to the monolayer scaffold and control groups. Histological ICRS scores were also significantly higher (p < 0.05) in the bilayer scaffold group compared to the control group. Type II collagen expression was higher (p < 0.05) in the bilayer scaffold group compared to the monolayer scaffold and control groups, although type I collagen expression was lower in comparison. In conclusion, this research suggests that the diclofenac-loaded bilayer scaffold effectively enhances cartilage and subchondral bone regeneration.

Subchondral defects resembling osteochondrosis dissecans in joint surfaces of the extinct saber-toothed cat Smilodon fatalis and dire wolf Aenocyon dirus.

Skeletal disease may hamper the behavior of large predators both living and extinct. We investigated the prevalence of osteochondrosis dissecans (OCD), a developmental bone disease affecting the joints, in two Ice Age predators: the saber-toothed cat Smilodon fatalis and dire wolf Aenocyon dirus. As published cases in modern Felidae and wild Canidae are rare, we predicted that subchondral defects resembling OCD would be rare in the extinct predators. We examined limb joints in juvenile and adult S. fatalis: 88 proximal humeri (shoulder), 834 distal femora (stifle), and 214 proximal tibiae. We also examined limb joints in juvenile and adult A. dirus: 242 proximal humeri, 266 distal femora, and 170 proximal tibiae. All specimens are from the Late Pleistocene Rancho La Brea fossil locality in Los Angeles, California, USA. While the Smilodon shoulder and tibia showed no subchondral defects, subchondral defects in the Smilodon femur had a prevalence of 6%; most defects were small (<7mm); and nine adult stifles with defects also showed osteoarthritis. Subchondral defects in the A. dirus femur had a prevalence of 2.6%; most defects were large (>12mm); and five stifles further developed mild osteoarthritis. Subchondral defects in the A. dirus shoulder had a prevalence of 4.5%; most defects were small, and three shoulders developed moderate osteoarthritis. No defects were found in the A. dirus tibia. Contrary to our prediction, we found a high prevalence of subchondral defects in the stifle and shoulder of S. fatalis and A. dirus resembling OCD found in humans and other mammals. As modern dogs affected by OCD are highly inbred, this high prevalence in the fossil taxa may suggest that they experienced inbreeding as they approached extinction. The deep-time history of this disease supports the need for monitoring of animal domestication, as well as conservation, to avoid unexpected surges in OCD under conditions like inbreeding.

Efficacy of Subchondroplasty in the Treatment of Pain Associated With Bone Marrow Lesions in the Osteoarthritic Knee.

Bone marrow lesions (BMLs) are common subchondral defects revealed by magnetic resonance imaging (MRI) in patients with osteoarthritis, often associated with pain and functional limitation. Subchondroplasty (SCP) is a relatively new technique in which bone substitute material (BSM) is injected inside BML areas to provide structural support to the subchondral bone, preventing its collapse and reducing pain. The purpose of this study was to characterize changes in pain, functional and radiological outcomes, conversion to knee replacement, and complications after SCP. We hypothesized that ≥70% of patients would achieve a reduction in pain of ≥4 points on a numeric rating scale (NRS) at a 6-month follow-up after SCP. Case series; Level of evidence, 4. Patients with symptomatic knee BMLs who underwent SCP were prospectively evaluated preoperatively and at 1, 6, 12, and 24 months postoperatively. Functional outcomes were measured with the NRS for pain, Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) scores. Radiographs and MRI were performed preoperatively and at 6- and 12-month follow-ups to verify edema healing and changes in bone structure. A total of 50 patients were included in the study. The mean follow-up was 26 months (24-30 months). Compared with preoperative values, the mean NRS score decreased at every follow-up point (P < .0001 for all) and the IKDC, WOMAC, and KSS scores improved significantly at 6- and 12-month follow-ups. At 6 months postoperatively, 27 patients (54%) registered a reduction on the NRS of ≥4 points. Postoperative MRI revealed a hypointense zone surrounded by a hyperintense signal at the injection site. Standard radiography showed osteoarthritis grade worsening in 4 (8%) patients. Knee replacement was performed in 11 patients -in 7 patients due to the worsening or persistence of disabling symptoms and in 4 patients due to the progression of osteoarthritis. The leakage of BSM occurred in 6 patients without any clinical consequences during the study period. About half of the study patients achieved a reduction in the NRS of 4 points at the 6-month follow-up after SCP. NCT04905394 (ClinicalTrials.gov identifier).

Хирургическое лечение импрессионного перелома наружного мыщелка большеберцовой кости (клинический случай)

INTRODUCTION: Treatment of intra-articular fractures of the proximal tibial metaepiphysis can often cause difficulties in accurate restoring of the congruence of the articular surfaces of the knee joint. Such fractures may be accompanied by subsidence of the articular surface and the formation of a subchondral defect. In the absence of displacement of bone fragments and preservation of congruence of the articular surfaces of the knee joint, such fractures can be treated conservatively. In the opposite case, there is a need for a complete restoration of the articular surface of the tibia. It should be noted that among all fractures of the tibial plateau, more than half are fractures of the lateral condyle, also accompanied by the presence of an impression. A clinical case of surgical treatment of a 62-year-old patient, BMI (body mass index) 39, with an intra-articular multi-comminuted impression fracture of the lateral condyle of the tibia with displacement of bone fragments is presented. The patient gave her written consent to the use of her clinical data for scientific purposes. Upon admission to hospital, a closed intra-articular fracture of the external condyle (Schatzker II) was diagnosed with fragmentation and articular surface impression of more than 5 mm, and the presence of a spongy bone defect with a volume of about 4 cm3 as a result of the impression. Surgical treatment was performed that consisted of open reposition and restoration of the congruence of the articular surface, with simultaneous plasty of the defect of the external condyle with an autograft taken from the iliac crest, followed by osteosynthesis of the external condyle with a plate and screws. On the follow up examination 9 months after the surgical treatment, the patient developed post-traumatic osteoarthrosis of the knee joint with severe pain. Some probable errors in the preparation of the patient for surgical treatment, preoperative planning, surgical treatment, recovery in the postoperative period, as well as functional and radiological results of treatment are presented for discussion. CONCLUSION: The development of post-traumatic osteoarthrosis in the treatment of tibial condylar fractures still remains an important problem in modern traumatology. Special attention in the treatment of such fractures should be given to preoperative planning, surgical technique and implant selection. It is important not to lose communication between the patient and the surgeon throughout the entire recovery period.

Nacre-mimetic hydroxyapatite/chitosan/gelatin layered scaffolds modifying substance P for subchondral bone regeneration

Nacre, exhibiting excellent mechanical strengths due to its hierarchical structures, becomes a potential model to design bone implants. Herein, we firstly fabricated nacre-mimetic hydroxyapatite/chitosan/gelatin (HA/CS/Gel) layered scaffolds and incorporated substance P (SP) peptides. The CS scaffolds with a layered architecture could regulate the deposition of HA nanoplates on the interlamellar CS sheets by using CaCO3 as precursors. The HA/CS/Gel layered scaffolds exhibited a great flexure strength of 11.42 MPa due to a brick-and-mortar structure. The biocompatible components, layered macropores and SP peptides in the HA/CS/Gel therapeutic scaffolds facilitated the spreading and proliferation mesenchymal stem cells (MSCs). Notably, the incorporation of SP peptides induced MSC osteogenic differentiation and extracellular matrix mineralization. Rabbit knee subchondral defect models further proved that the HA/CS/Gel-SP layered scaffolds promoted in vivo subchondral bone regeneration. Hence, the combination of nacre-mimetic bone implants and therapeutic drugs may become an attractive strategy for subchondral bone regeneration.

Preparation of Assemblable Chondral and Subchondral Bone Microtissues for Osteochondral Tissue Engineering.

Microtissues exhibit great advantages in injecting with minimum invasiveness, mimicking natural tissues, and promoting tissue regeneration. However, very few studies have focused on the construction of osteochondral microtissues that could simultaneously support hyaline-like cartilage and bone tissue regeneration. In this study, chondral microtissues that could favor the formation of hyaline-like cartilages and subchondral bone microtissues that could repair subchondral defects to support the neo-generated cartilages were successfully constructed for osteochondral tissue engineering. For chondral repair, the developed chondral microgels with high porosity and hydrophilicity could make cells spherical, favor the formation of cell aggregates, and show an excellent differentiation effect toward hyaline-like cartilage, thus contributing to the production of chondral microtissues. For subchondral bone repair, the fabricated subchondral microgels realize cell adhesion and proliferation and support the osteogenic differentiation of stem cells, thus favoring the formation of subchondral bone microtissues. The injectable chondral and subchondral bone microtissues could be stably assembled by Michael addition reaction between sulfhydryl groups of microtissues and double bonds of hydrophilic macromolecular cross-linker. At 12 weeks postimplantation, osteochondral microtissues could support the reconstruction of osteochondral-like tissues. The present study provides new insight into the microtissues for repair of osteochondral tissues.

Repairing of Subchondral Defect and Articular Cartilage of Knee Joint of Rabbit by Gadolinium Containing Bio-Nanocomposites

A variety of gadolinium (Gd) based nanoparticles (NPs) were synthesized due to the unique magnetic properties of Gd-containing rare earth compounds and the particularity of micro/nano-materials, which were then incorporated into hydroxyapatite (HA) to obtain inorganic-organic composite materials. Then, HA/Gd NPs containing slow-release transforming growth factor (TGF-β1) were harvested. Adipose-derived stem cells (ADSCs) were extracted from the adipose tissue of a four-month-old New Zealand white rabbit. HA/Gd NPs were attached to absorbable gelatin sponge to obtain HA/Gd NPs/gelatin sponge composite scaffold. In addition, the third generation ADSCs were taken and cultured in the composite scaffold, so that ADSCs-HA/Gd bio-nanocomposites were obtained. The in vitro culture test of osteoblast MC3T3-E1 showed that Gd-containing NPs had good biocompatibility. The prepared HA/Gd NPs loaded with TGF-β1 were spherical, with an average particle size of (9.16 ± 3.16) μm. The NPs were easy to aggregate and adherent. Enzyme-linked immunosorbent assay (ELISA) test results showed that TGF-β1 in NPs was sustained and released continuously for 29 days. HA/Gd NPs/gelatin sponge composite scaffold combined with ADSCs were co-cultured for three days, and the electron microscope showed that the HA/Gd NPs were dispersed, and the cells could adhere and grow well. Then, animal models of rabbit knee articular cartilage defects were established and were rolled into three groups (ADSCs-HA/Gd nano group, HA/Gd nano scaffold group, and blank control). The repair area of the rabbit knee of ADSCs-HA/Gd nano group was smooth and flat, the scaffold was absorbed, the toluidine blue stain was positive, and the type II collagen immunohistochemical stain was positive. In general, ADSCs-HA/Gd nanomaterials were helpful for chondrogenic cell differentiation and had certain adoption prospects in the field of tissue engineering to repair cartilage defects.

Synergistic effects of Indian hedgehog and sonic hedgehog on chondrogenesis during cartilage repair.

Sonic hedgehog (Shh) and Indian hedgehog (Ihh) have been shown to control the induction of early cartilaginous differentiation. However, it is unclear whether Ihh and Shh exert synergistic effects on chondrogenesis during articular cartilage repair. Herein, we investigate the effects of chondrogenesis of bone-derived mesenchymal stem cells (BMSCs) following co-transfection with Shh and Ihh via adenoviral vectors in vitro and in vivo. A rotary cell culture system (RCCS) and Cytodex 3 microcarriers were used to create a stereoscopic dynamic environment for cell culture. In the RCCS environment, BMSCs co-transfected with Ihh and Shh displayed stronger chondrogenic differentiation and chondrogenesis than BMSCs transfected with Ihh or Shh alone, and exhibited higher expression levels of Sox 9, ACAN and collagen II, stronger toluidine blue and collagen II immunohistochemical staining. After transplanted into the osteochondral defect at 8weeks, Ihh/Shh co-transfected BMSCs showed a significantly better cartilage repair than BMSCs transfected with Ihh or Shh alone. Ihh and Shh have synergistic effects on the induction of chondrogenic differentiation and chondrogenesis under a microgravity environment, and help to repair damaged cartilage and reverse subchondral defects during the early stages.

Treatment of tibial plateau fractures with a novel fenestrated screw system for delivery of bone graft substitute.

The purpose of this study was to describe the incidence of subsidence in patients with AO/OTA 41 (tibial plateau) fractures which were repaired with a novel fenestrated screw system to used to deliver CaPO4 bone substitute material to fill the subchondral void and support the articular reduction. Patients with unicondylar and bicondylar tibial plateau fractures were treated according to the usual technique of two surgeons. After fixation, the Zimmer Biomet N-Force Fixation System®, a fenestrated screw that allows for the injection of bone substitute was placed and used for injection of the proprietary calcium phosphate bone graft substitute into the subchondral void. For all included patients, demographic information, operative data, radiographs, and clinic notes were reviewed. Patients were considered to have articular subsidence if one or more of two observations were made when comparing post-operative to their most recent clinic radiographs: > 2mm change in the distance between the screw and the lowest point of the tibial plateau, > 2mm change in the distance between the screw and the most superior aspect of the plate. Data were analyzed to determine if there were any identifiable risk factors for complication, reoperation, or subsidence using logistic regression. Statistical significance was set at p < 0.05. 34 patients were included with an average follow-up of 32.03 ± 22.52weeks. There were no overall differences between height relative to the medial plateau or the plate. Two patients (5.9%) had articular subsidence. Six patients (15.2%) underwent reoperation, two (6%) for manipulations under anaesthesia due to arthrofibrosis, and four (12%) due to infections. There were 6 (19%) total infections as 2 were superficial and required solely antibiotics. One patient had early failure. Use of a novel fenestrated screw system for the delivery of CaPO4 BSM results in articular subsidence and complication rates similar to previously published values and appears to be a viable option for addressing subchondral defects in tibial plateau fractures. IV.

Quantitative 3-T Magnetic Resonance Imaging After Matrix-Associated Autologous Chondrocyte Implantation With Autologous Bone Grafting of the Knee: The Importance of Subchondral Bone Parameters

Background: Matrix-associated autologous chondrocyte implantation (MACI) with autologous bone grafting (ABG) is an effective surgical treatment for osteochondral defects. Quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as noninvasive biomarkers to assess the biochemical composition of cartilage repair tissue. Purpose: To evaluate the association of quantitative MRI parameters of cartilage repair tissue and subchondral bone marrow with magnetic resonance morphologic and clinical outcomes after MACI with ABG of the knee. Study Design: Case series; Level of evidence, 4. Methods: Qualitative and quantitative 3 T MRI of the knee was performed in 21 patients (16 male) at 2.5 years after MACI with ABG at the medial (18/21) or lateral (3/21) femoral condyle for the treatment of osteochondral defects. Morphologic MRI sequences were assessed using MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 scores. T2 relaxation time measurements for the assessment of cartilage repair tissue (CRT2) were obtained. Single-voxel magnetic resonance spectroscopy was performed in underlying subchondral bone marrow (BM) and at both central femoral condyles. The presence of pain and Tegner scores were noted. Statistical analyses included Student t tests, correlation analyses, and multivariate regression models. Results: The mean defect size was 4.9 ± 1.9 cm2. At a follow-up of 2.5 ± 0.3 years, 9 of 21 patients were asymptomatic. Perfect defect filling was achieved in 66.7% (14/21) of patients. MOCART 2.0 scores (74.1 ± 18.4) did not indicate pain (68.3 ± 19.0 [pain] vs 81.7 ± 15.4 [no pain]; P = .102). However, knee pain was present in 85.7% (6/7) of patients with deep bony defects (odds ratio, 8.0; P = .078). Relative CRT2 was higher in hypertrophic cartilage repair tissue than in repair tissue with normal filling (1.54 ± 0.42 vs 1.13 ± 0.21, respectively; P = .022). The underlying BM edema–like lesion (BMEL) volume was larger in patients with underfilling compared with patients with perfect defect filling (1.87 ± 1.32 vs 0.31 ± 0.51 cm3, respectively; P = .002). Patients with severe pain showed a higher BMEL volume (1.2 ± 1.3 vs 0.2 ± 0.4 cm3, respectively; P = .046) and had a higher BM water fraction (26.0% ± 12.3% vs 8.6% ± 8.1%, respectively; P = .026) than did patients without pain. Conclusion: Qualitative and quantitative MRI parameters including the presence of subchondral defects, CRT2, BMEL volume, and BM water fraction were correlated with cartilage repair tissue quality and clinical symptoms. Therefore, the integrity of subchondral bone was associated with outcomes after osteochondral transplantation.

Arthroscopic-Assisted Intraosseous Bioplasty of the Acetabulum

Intraosseous bioplasty (IOBP), has been previously described for arthroscopic-assisted treatment of subchondral bone cysts in the proximal tibia associated with early stages of knee osteoarthritis (OA). This technique entails combining bone marrow aspirate concentrate or concentrated platelet-rich plasma with demineralized bone matrix as a bone substitute before injecting into a subchondral bone defect under fluoroscopic guidance. The principles of IOBP as a procedure that combines core decompression with biologic bone substitute augmentation can be extended to treat subchondral bone marrow lesions such as acetabular and femoral cysts in degenerative hip OA. Intraosseous bioplasty of the hip, in particular the acetabulum, when done using this technique, is a useful alternative that can be beneficial in treating young patients with early hip arthritis to achieve successful outcomes while delaying more invasive procedures. The Technical Note described here presents a step-by-step approach, including tips and pearls for arthroscopic-assisted IOBP with decompression of the subchondral cyst in the acetabulum followed by bone substitute injection under fluoroscopic guidance. We believe this method is a safe and reproducible way to treat subchondral defects in young patients with signs of early osteoarthritis of the hip joint.

Modified advanced core decompression (mACD)

The modified advanced core decompression (mACD) combines the advantages of alow invasive core decompression with maximal removal of osteonecrotic bone and abiologic reconstruction of the resulting bone defect. Avascular (atraumatic) osteonecrosis of the femoral head (ARCO stageII). Subchondral fractures (ARCO stageIII); advanced osteoarthritis (e.g., ACRO stageIV); persisting risk factors such as high-dose corticoid therapy, chemotherapy, alcohol abuse; open growth plates; history of side effects or intolerance to components of the applied bone substitute; lack of patient compliance; osteomyelitis or other septic conditions. Supine positioning on the operation table, skin disinfection, and sterile draping. Skin incision and core decompression using a3.2 mm guide wire. Removal of abone cylinder from anonaffected area of the femoral neck using ahollow trephine. Drilling of the osteonecrotic area over the applied wire up to 5 mm to the subchondral bone under fluoroscopy, insertion of an expandable bone knife and removal of the osteonecrotic bone supported by acurette. Bone grafting of the autologous bone into the subchondral defect zone and filling of the drill canal by resorbable bone substitute. Bed rest for 24 h, then partial weight bearing (20 kg) on crutches for 2-6weeks depending on the bone quality in the defect zone and the applied bone substitute. Midterm superiority (2years) in hip survival of the mACD over advanced core depression and core depression, especially in ARCO stageII.

Enhancing the Efficacy of Stem Cell Therapy with Glycosaminoglycans.

SummaryHuman mesenchymal stem cell (hMSC) therapy offers significant potential for osteochondral regeneration. Such applications require their ex vivo expansion in media frequently supplemented with fibroblast growth factor 2 (FGF2). Particular heparan sulfate (HS) fractions stabilize FGF2-FGF receptor complexes. We show that an FGF2-binding HS variant (HS8) accelerates the expansion of freshly isolated bone marrow hMSCs without compromising their naivety. Importantly, the repair of osteochondral defects in both rats and pigs is improved after treatment with HS8-supplemented hMSCs (MSCHS8), when assessed histologically, biomechanically, or by MRI. Thus, supplementing hMSC culture media with an HS variant that targets endogenously produced FGF2 allows the elimination of exogenous growth factors that may adversely affect their therapeutic potency.

The horse as a model for translational orthopedic research: examples of studies on the regeneration of cartilage and bone conducted in Costa Rica

The paper provides results published or to be published of long-term in vivo equine studies to evaluate techniques of possible regenerative matrices of cartilage and bone, by means of cell-free implants or stimulation of the bone marrow. From the fixation techniques analyzed, it can be concluded that the best alternatives are the pressure technique for subchondral defects and a novel hydrogel with self-adhesive capacity for chondral defects. The equine coxal tuberosity was used for the first time as a model for regeneration studies of bone defects, analyzing scaffolds based on tricalcium phosphate, polymers and nanoparticles, by means of 3-D printing. Osteoconductivity, osteoinductivity, and the importance of microporosity were documented.Given that decellularized materials do not always give significant desired results in the regeneration of cartilage, it is important to conduct long-term studies. The technique of nanofracture and a novel self-adhesive hydrogel in the knee of the equine showed promising preliminary results in the regeneration of cartilage.The knee and the coxal tuberosity of the horse represent models of studying cartilage and bone regeneration in a true translational sense as a source of highly valuable information for clinical studies, for both horses and humans.

Sonic hedgehog promotes chondrogenesis of rabbit bone marrow stem cells in a rotary cell culture system

BackgroundSonic hedgehog (Shh) is an important signalling protein involved in the induction of early cartilaginous differentiation. Herein, we demonstrate that Shh markedly induces chondrogenesis of rabbit bone marrow stromal cells (BMSCs) under microgravity conditions, and promotes cartilage regeneration.ResultsIn the rotary cell culture system (RCCS), chondrogenic differentiation was revealed by stronger Toluidine Blue and collagen II immunohistochemical staining in the Shh transfection group, and chondroinductive activity of Shh was equivalent to that of TGF-β. Western blotting and qRT-PCR analysis results verified the stronger expression of Sox9, aggrecan (ACAN), and collagen II in rabbit BMSCs treated with Shh or TGF-β in a microgravity environment. Low levels of chondrogenic hypertrophy, osteogenesis, and adipogenesis-related factors were detected in all groups. After transplantation in vivo, histological analysis revealed a significant improvement in cartilage and subchondral repair in the Shh transfection group.ConclusionsThese results suggested that Shh signalling promoted chondrogenesis in rabbit BMSCs under microgravity conditions equivalent to TGF-β, and improved the early stages of the repair of cartilage and subchondral defects. Furthermore, RCCS provided a dynamic culture microenvironment conducive for cell proliferation, aggregation and differentiation.

Cartilage tissue engineering combining microspheroid building blocks and microneedle arrays

ABSTRACTPurpose: Scaffold-free cartilage tissue engineering circumvents issues with scaffold seeding, potential toxicity response, and impaired host integration. However, precisely controlling and maintaining a scaffold-free construct shape have been challenging. We explored the feasibility of microneedle arrays to print tissue using cellular microspheroids as building blocks.Materials and Methods: Human embryonic-derived mesenchymal stem cells or infrapatellar fat pad mesenchymal stem cells were used to create microspheroids of 500 µm in diameter, which were assembled on microneedle arrays in a predefined arrangement using a robotic system under computer vision. Microspheroids on microneedles were cultured to permit fusion into a tissue construct. Infrapatellar fat pad mesenchymal stem cell constructs were either implanted into chondral defects created in human osteoarthritic cartilage explants or maintained on the microneedle array for 3 weeks. Embryonic-derived mesenchymal stem cell constructs were designed to be press-fit into 3 mm subchondral defects in New Zealand White rabbits and maintained for up to 8 weeks to assess retention, early tissue repair, and more mature cartilage regeneration.Results: Microspheroids of both cell types fused together in culture to form neotissues of predefined shape and size. Infrapatellar fat pad mesenchymal stem cell neotissues expressed high levels of chondrogenic genes and integrated with the surrounding osteoarthritic host cartilage. Embryonic-derived mesenchymal stem cell constructs generated chondrogenic neotissue in vivo as early as 2 weeks and more mature tissue by 8 weeks with increased glycosaminoglycan deposition.Conclusions: We constructed defined scaffold-free shapes by bioprinting and fusing microspheroids. Proof of concept was shown in the repair of ex vivo osteoarthritic human cartilage and in vivo rabbit osteochondral (OC) defects.

An elastin-like recombinamer-based bioactive hydrogel embedded with mesenchymal stromal cells as an injectable scaffold for osteochondral repair.

The aim of this study was to evaluate injectable, in situ cross-linkable elastin-like recombinamers (ELRs) for osteochondral repair. Both the ELR-based hydrogel alone and the ELR-based hydrogel embedded with rabbit mesenchymal stromal cells (rMSCs) were tested for the regeneration of critical subchondral defects in 10 New Zealand rabbits. Thus, cylindrical osteochondral defects were filled with an aqueous solution of ELRs and the animals sacrificed at 4 months for histological and gross evaluation of features of biomaterial performance, including integration, cellular infiltration, surrounding matrix quality and the new matrix in the defects. Although both approaches helped cartilage regeneration, the results suggest that the specific composition of the rMSC-containing hydrogel permitted adequate bone regeneration, whereas the ELR-based hydrogel alone led to an excellent regeneration of hyaline cartilage. In conclusion, the ELR cross-linker solution can be easily delivered and forms a stable well-integrated hydrogel that supports infiltration and de novo matrix synthesis.