Biomimetic Osteochondral Scaffold Research Articles

A Biomimetic Osteochondral Scaffold Augmented With Filtered Bone Marrow Aspirate for the Treatment of Joint Surface Lesions in the Knee.

Multilayered osteochondral scaffolds are becoming increasingly utilized for the repair of knee joint surface lesions (KJSLs). However, the literature on predictive factors is rather limited. To (1) evaluate the clinical outcomes and safety of a combined single-step approach using a biomimetic collagen-hydroxyapatite scaffold (CHAS) and filtered bone marrow aspirate (fBMA) for the treatment of KJSLs and (2) identify significant predictors of the treatment outcomes. Case series; Level of evidence, 4. All patients who underwent surgery because of a KJSL (size ≥1.5 cm2; International Cartilage Regeneration & Joint Preservation Society grades 3-4) using the combination above were selected from a hospital registry database (100 patients; minimum 2-year follow-up). Patient characteristics, medical history, knee joint and lesion status, intraoperative details, and cellular parameters of the injected fBMA were collected. The arthroscopic evaluation of chondral and meniscal tissue quality in all knee compartments was performed using the Chondropenia Severity Score. Treatment outcomes were determined clinically using patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, EuroQol-5 Dimensions-3 Levels, EuroQol-Visual Analog Scale, and Tegner Activity Scale) and by assessing the occurrence of serious adverse events and graft failure. Multivariable regression analysis was performed to identify significant predictors of the treatment outcomes. At a mean follow-up of 54.2 ± 19.4 months, 78 (87%) patients completed the questionnaires with significant improvements toward the baseline (P < .00625): KOOS Pain subscale from 62 ± 17 to 79 ± 18, KOOS Total score from 57 ± 16 to 70 ± 20, EuroQol-Visual Analog Scale from 61 ± 21 to 76 ± 16, EuroQol-5 Dimensions-3 Levels from 0.57 ± 0.20 to 0.80 ± 0.21, and Tegner Activity Scale from 2.8 ± 1.5 to 3.9 ± 1.9. The graft failure rate was 4%. A longer duration of preoperative symptoms, previous surgery, larger lesions, older age, and female sex were the main negative predictors for the treatment outcomes. The Chondropenia Severity Score and the number of fibroblast colony-forming units in fBMA positively influenced some of the clinical results and safety. A CHAS augmented with fBMA proved to be an adequate and safe approach for the treatment of KJSLs up to midterm follow-up. Based on the subanalysis of predictive factors, the surgical intervention should be performed in a timely and precise manner to prevent lesion enlargement, deterioration of the general knee cartilage status, and recurrent surgical procedures, especially in older and female patients. When a CHAS is used, the quantity of MSCs seems to play a role in augmentation. NCT06078072 (ClinicalTrials.gov identifier).

Dynamic process enhancement on chitosan/gelatin/nano-hydroxyapatite-bone derived multilayer scaffold for osteochondral tissue repair

Accurate repair of osteochondral defects is a great challenge due to the complex structure of osteochondral defects. The current study aims to prepare a biomimetic osteochondral gradient scaffold based on chitosan, gelatin and nano-hydroxyapatite and bone-derived materials for repair cartilage defects. Hereon, the chitosan/gelatin/nano-hydroxyapatite multilayer scaffold with complex hierarchical structure using iterative hierarchical method is prepared to simulate the structure of natural cartilage. And porcine femur in distal metaphysis was treated by chemical decellularization, deproteinization, decalcification, and degreasing to obtain the bone-derived scaffold simulating subchondral bone layer. We also used a spinner bioreactor for the in vitro modeling of the microenvironment which can promote adipose mesenchymal stem cell (ADSCs) recruitment into the chitosan/gelatin/nano-hydroxyapatite-bone derived multilayer scaffold under physiological flow conditions. Biological experiments have shown that osteochondral layered materials can induce ADSCs to differentiate into chondrocytes and osteoblasts and exhibit chondrogenic and osteogenic phenotypes similar to natural tissues, respectively. Furthermore, the expression both of the chondrogenic gene (Col II, ACAN, and Sox9) and osteogenic gene (Runx2, OCN and Col I) of ADSCs differentiated by mechanical stimulation were increased. These results indicate that osteochondral materials and dynamic environment are the key factors to improve cell regulation or signal molecule transfer function, and provide a feasible plan for osteochondral regeneration for future medical services.

Cell-Free Biomimetic Osteochondral Scaffold for the Treatment of Knee Lesions: Clinical and Imaging Results at 10-Year Follow-up

Background: Cell-free devices have been introduced to restore osteochondral defects, avoiding the limitations of cell-based procedures. Among these, an osteochondral scaffold made of type I collagen and hydroxyapatite has been investigated with promising results up to medium-term follow-up. However, the clinical and imaging results over time still need to be documented. Purpose: To evaluate the clinical outcome and tissue maturation at long-term follow-up after the implantation of the osteochondral scaffold. Study Design: Case series; Level of evidence, 4. Methods: A total of 24 patients (7 women, 17 men; age, 36 ± 9.5 years) underwent surgical implantation of the osteochondral scaffold and were prospectively evaluated before surgery, at 2-, 5-, and 10-year follow-up. The mean defect size was 2.9 ± 1.4 cm2. Patients were evaluated using the International Knee Documentation Committee (IKDC) subjective and objective scores, and the activity level was documented with the Tegner score. Magnetic resonance imaging (MRI) evaluation involved the use of the magnetic resonance observation of cartilage repair tissue score combined with 5 more variables focused on the bone layer. Results: A statistically significant improvement of all clinical scores was documented from the baseline to the final evaluation. The IKDC subjective score improved from the preoperative level to 2 years (41 ± 13.2 and 77.1 ± 14.6, respectively) (P < .0005), with stable results up to 10 years (77.4 ± 19.4). The IKDC objective score changed from 52% of normal and nearly normal knees before the treatment to 84% at 10 years (P < .0005). Tegner sports activity at the final evaluation (3.8 ± 1.7) was higher compared with the preoperative level (1.6 ± 1.1; P < .05), but it remained significantly lower compared with the preinjury level (5.5 ± 2.6; P < .05). Treatment failed in 1 patient. Persisting graft alterations were observed on MRI scans, although without correlating with the clinical outcome. Conclusion: The regenerative potential of this scaffold is limited, as demonstrated by the signal alterations persisting over time on MRI scans. On the other hand, the clinical improvement was significant and stable over time both in terms of subjective and objective outcomes, including activity level, with overall good results.

A case report of femoral head fracture with osteochondral lesion treated by osteosynthesis and biomimetic scaffold: 2-year clinical and radiological follow-up

The aim of the present study was to present clinical and radiological outcome of a hip fracture-dislocation of the femoral head treated with biomimetic osteochondral scaffold.An 18-year-old male was admitted to the hospital after a motorcycle-accident. He presented with an obturator hip dislocation with a type IVA femoral head fracture according to Brumback classification system. The patient underwent surgery 5 days after accident. The largest osteochondral fragment was reduced and stabilized with 2 screws, and the small fragments were removed. The residual osteochondral area was replaced by a biomimetic nanostructured osteochondral scaffold. At 1-year follow-up the patient did not complain of hip pain and could walk without limp. At 2-year follow-up he was able to run with no pain and he returned to practice sports. Repeated radiographs and magnetic resonance imaging studies of the hip showed no signs of osteoarthritis or evidence of avascular necrosis. A hyaline-like signal on the surface of the scaffold was observed with restoration of the articular surface and progressive decrease of the subchondral edema.The results of the present study showed that the biomimetic nanostructured osteochondral scaffold could be a promising and safe option for the treatment of traumatic osteochondral lesions of the femoral head.Study Design: Case report.

Current researches on design and manufacture of biopolymer-based osteochondral biomimetic scaffolds

Currently, osteochondral (OC) tissue engineering has become a potential treatment strategy in repairing chondral lesions and early osteoarthritis due to the limited self-healing ability of cartilage. However, it is still challenging to ensure the integrity, physiological function and regeneration ability of stratified OC scaffolds in clinical application. Biomimetic OC scaffolds are attractive to overcome the above problems because of their similar biological and mechanical properties with native OC tissue. As a consequence, the researches on biomimetic design to achieve the tissue function of each layer, and additive manufacture (AM) to accomplish composition switch and ultrastructure of personalized OC scaffolds have made a remarkable progress. In this review, the design methods of biomaterial and structure as well as computer-aided design, and performance prediction of biopolymer-based OC scaffolds are presented; then, the characteristics and limitations of AM technologies and the integrated manufacture schemes in OC tissue engineering are summarized; finally, the novel biomaterials and techniques and the inevitable trends of multifunctional bio-manufacturing system are discussed for further optimizing production of tissue engineering OC scaffolds.

Treatment of Juvenile Knee Osteochondritis Dissecans with a Cell-Free Biomimetic Osteochondral Scaffold: Clinical and MRI Results at Mid-Term Follow-up.

Osteochondral surgical procedures have been described for the treatment of unfixable osteochondritis dissecans (OCD), but only few of them have been studied for juvenile OCD (JOCD) lesions. A cell-free biomimetic osteochondral scaffold showed positive results in adult patients. The aim of this study was to evaluate the results of this scaffold for the treatment of knee JOCD at mid-term follow-up. Twenty patients (14 males, 6 females) were included in this study. Mean age was 16.2 ± 1.4 years, average defect size was 3.2 ± 1.8 cm2, and mean symptoms duration was 20.2 ± 17.9 months. After the implantation of the osteochondral collagen-hydroxyapatite scaffold (Maioregen, Fin-Ceramica, Faenza, Italy), patients were evaluated preoperatively and prospectively at 1, 2, and at final mean follow-up of 6 years (range 5-7 years) with International Knee Documentation Committee (IKDC) subjective and objective, Tegner, and EuroQol visual analogue scale (VAS) scores. MRI evaluation was performed with the MOCART 2.0 score. All scores showed a significant improvement. IKDC subjective score went from 50.3 ± 17.4 preoperative score to 75.3 ± 14.6 at 1 year (P = 0.002), 80.8 ± 14.6 at 2 years and 85.0 ± 9.3 at 6 years. The Tegner score improved from the preoperative evaluation of 2.6 ± 1.4 to 5.5 ± 2.0 at 6 years (P < 0.0005), although without reaching the level registered before the onset of symptoms. A longer symptoms duration influenced negatively IKDC subjective and Tegner scores up to 2 years (P = 0.003 and P = 0.002, respectively) but did not affect the final outcome. Lesion size did not affect the final result. The MOCART 2.0 score showed a significant improvement between 1-year and final follow-up, but with persisting subchondral alterations. This study demonstrated a clinical improvement stable over time with a high survival rate, although with persisting abnormal MRI findings, especially at subchondral bone level. This procedure can be considered a suitable option for the treatment of young patients affected by knee OCD. Level of evidence. Case series, level IV.

Autologous chondrocytes versus filtered bone marrow mesenchymal stem/stromal cells for knee cartilage repair-a prospective study.

To document clinical, radiologic, and cellular data of a prospective patient series treated by a tri-layer collagen-hydroxyapatite biomimetic osteochondral scaffold (CHAS) intra-operatively seeded with cultivated autologous chondrocytes (AC) or with filtered bone marrow stem/stromal cells (fBMSC) to address chronic osteochondral knee lesions. Thirty-six consecutive patients (15 to 59years) with chronic osteochondral lesions (1.8-10cm2) in the condylar or patellofemoral knee surfaces were enrolled. Lesions were covered with CHAS fixed with a fibrin glue. The superficial layer of CHAS was intra-operatively injected with active cells: in initial fivepatients, ACs were put directly onto dry CHAS (dry-AC); next, eightAC patients had CHAS moistened with cell culture media (media-AC), while the tourniquet was released allowing blood soaking of CHAS in the rest (14 blood-AC, 9 blood-fBMSC). Seventeen (50%) patients required different concomitant procedures. All patients were followed for serious adverse events (SAE) or graft failures; clinical, radiographic, and MRI evaluation was conducted. Cellular data on the injected cells were assessed. At a follow-up of 39months (16-81), 17 patients required an additional surgical intervention: sevengraft-related SAE (early post-operative synovitis and/or arthrofibrosis) were registered (3 dry-AC, 3 media-AC, 1 blood-fBMSC). There were two graft failures (1 dry-AC, 1 blood-fBMSC) for secondary reasons. All clinical scores significantly improved from pre- to post-operative values: IKCD subjective 44 to 65; IKDC examination (9/17/5/5) to (20/10/5/1); KOOS (P61/S59/ADL67/Sp32/QoL31) to (P79/S75/ADL84/Sp55/QoL51); Tegner activity scale 3.3 to 4.4. There was evidence of radiographic osteoarthritis progression-Kellgren-Lawrence 1.0 to 1.5. MOCART scores at the final follow-up averaged 71 (10 to 95). Graft-type analysis demonstrated an increased rate of graft-related SAE in dry-AC and media-AC, but their final outcomes were equivalent. Cellular data of AC at the implantation were as follows: cells in suspension 9.2 × 106, viability 95%. In blood-fBMSC group, a cell suspension with 87% viability was injected, which contained 1156 CFU-Fs. CHAS with intra-operative seeding of active cells, either AC or fBMSC, led to an overall successful outcome for the treatment of chronic osteochondral lesions in the knee. Blood soaking of CHAS in situ before cell seeding significantly decreased early post-operative adverse events, such as synovitis and arthrofibrosis.

Role of the Calcified Cartilage Layer of an Integrated Trilayered Silk Fibroin Scaffold Used to Regenerate Osteochondral Defects in Rabbit Knees.

The repair of osteochondral defects remains challenging, given the complexity of native osteochondral tissue and the limited self-repair capacity of cartilage. Osteochondral tissue engineering is a promising strategy. Here, we fabricated a biomimetic osteochondral scaffold using silk fibroin and hydroxyapatite, including a calcified cartilage layer (CCL). We studied the role played by the CCL in terms of cell viability in vivo. We established osteochondral defects in rabbit knees to investigate the effects of CCL-containing scaffolds with or without adipose tissue-derived stem cells (ADSCs). We evaluated osteochondral tissue regeneration by calculating gross observational scores, via histological and immunohistochemical assessments, by performing quantitative biochemical and biomechanical analyses of new osteochondral tissue, and via microcomputed tomography of new bone at 4, 8, and 12 weeks after surgery. In terms of surface roughness and integrity, the CCL + ADSCs group was better than the CCL and the non-CCL + ADSCs groups at all time points tested; the glycosaminoglycan and collagen type II levels of the CCL + ADSCs group were highest, reflecting the important role played by the CCL in cartilage tissue repair. Subchondral bone smoothness was better in the CCL + ADSCs group than in the non-CCL + ADSCs and CCL groups. The CCL promoted smooth subchondral bone regeneration but did not obviously affect bone strength or quality. In conclusion, a biomimetic osteochondral scaffold with a CCL, combined with autologous ADSCs, satisfactorily regenerated a rabbit osteochondral defect. The CCL enhances cartilage and subchondral bone regeneration.

Cell-Free Osteochondral Scaffold for the Treatment of Focal Articular Cartilage Defects in Early Knee OA: 5 Years' Follow-Up Results.

The purpose of this study was to investigate the clinical results at five years’ follow-up of a tri-layered nanostructured biomimetic osteochondral scaffold used for focal articular cartilage defects in patients meeting the criteria of early osteoarthritis (EOA). The study population comprised 22 patients (mean age: 39 years), prospectively assessed before surgery, at 24 and 60 months’ follow-up. Inclusion criteria were: at least two episodes of knee pain for more than 10 days in the last year, Kellgren-Lawrence OA grade 0, I or II and arthroscopic or MRI findings according to the European Society of Sports Traumatology, Knee Surgery & Arthroscopy (ESSKA) criteria. Clinical results demonstrated significant improvement in International Knee Documentation Committee (IKDC) subjective and objective scores and in Tegner score, although activity level never reached the pre-injury level. The complication rate of this study was 8.3%. Two patients underwent re-operation (8.3%), while a comprehensive definition of failure (including both surgical and clinical criteria) identified four failed patients (16.6%) at this mid-term follow-up evaluation. The use of a free-cell osteochondral scaffold represented a safe and valid alternative for the treatment of focal articular cartilage defects in the setting of an EOA, and was able to permit a significant clinical improvement and stable outcome with low complication and failure rates.

Cartilage and Bone Serum Biomarkers as Novel Tools for Monitoring Knee Osteochondritis Dissecans Treated with Osteochondral Scaffold.

Knee osteochondritis dissecans (OCD) is a focal disease of the joint characterized by modifications of bone and cartilage tissues. Biomimetic osteochondral scaffolds are used to restore these tissues. The aim of this prognostic prospective cohort study was to evaluate serum biomarkers of cartilage (fragments or propeptide of type II collagen: CTXII, C2C, and CPII) and bone (tartrate-resistant acid phosphatase (TRAP) 5b and osteocalcin (OC)) turnover during follow-up of patients treated with an osteochondral scaffold, to identify which were related to healing outcome and clinical score. We found that cartilage (CPII) and bone (OC) synthetic biomarkers were significantly increased during the first-year follow-up, while the respective degradative markers (CTXII, C2C, and TRAP5b) were not modulated. Only CTXII/CPII and C2C/CPII cartilage ratios were significantly modulated, evidencing a higher remodeling of cartilage compared to bone tissue. Cartilage and bone single biomarkers or ratios at one-year follow-up showed values close to or similar to those of healthy subjects. International Knee Documentation Committee (IKDC) score significantly increased from T0 to T2, while the Tegner score did not. Taking into consideration an IKDC score > 70 as clinical success, we found that all OCD cases with both CPII (> 300 pg/ml) and C2C/CPII (<0.35) presented IKDC scores of clinical success. OCD patients treated with an osteochondral scaffold showed an improvement at one-year follow-up, evidenced by both clinical and serum cartilage biomarkers. These data confirmed that cartilage and bone remodeling took place and showed that systemic biomarkers represent a sensitive tool for monitoring OCD patients during the follow-up.

Use of a Biomimetic Scaffold for the Treatment of Osteochondral Lesions in Early Osteoarthritis.

The aim of this study is to investigate clinical and radiographic outcomes of a biomimetic scaffold for the treatment of osteochondral knee lesions in patients with early OA. Study population was represented by 26 patients with a mean age of 44 years affected by early OA. Inclusion criteria were two episodes of knee pain for more than 10 days in the last year, Kellgren-Lawrence OA grade 0 or I or II, and arthroscopic findings of cartilage defects. Nineteen patients had a previous surgery, 11 of which were revision surgeries of osteochondral unit. All patients were treated with a biomimetic scaffold with a tri-layered structure of type I equine collagen and magnesium-enriched hydroxyapatite. Clinical outcomes were evaluated using the IKDC, Lysholm, VAS, KOOS, and Tegner scores at baseline and at an average follow-up of 35 months. Magnetic resonance imaging (MRI) was performed at follow-up time in 19 patients. Clinical outcomes showed significant improvement in VAS, Lysholm, IKDC subjective score, and KOOS subscales in 69% of the patients. Complication rate of this cases series was 11%, with no surgical failure, although 31% of patients did not reach a significant improvement and were thus considered as clinical failure. MRI analysis showed integration of the scaffold only in 47% of the patients, with partial regeneration of the subchondral bone. No correlation between clinics and radiological images was found. The use of a biomimetic osteochondral scaffold in the setting of an early OA, alone or associated with other procedures, appeared to be a valid and safe option, able to provide good and stable clinical outcomes with high patient's satisfaction and low complication rate.

Osteochondral tissue engineering based on biomimetic osteochondral scaffold contained calcified cartilage layer com-pounding with ADSCs in vivo

Objective The biomimetic osteochondral scaffold contained calcified cartilage layer(CCL) was fabricated us-ing slik fibroin (SF) and hydroxyapatite (HA) for materials. To investigate effects of biomimetic osteochondral scaffold contained CCL compounding with ADSCs on regeneration of the osteochondral defect on the rabbit knee, explore the feasibility of this design as a concept of osteochondral tissue engineering. Methods We fabricated a novel biomimetic osteochondral scaffold with CCL using SF and HA by the combination of paraffin-sphere leaching and modified temperature gradient-guided thermal-induced phase separation (TIPS) technique. The pore size, porosity, and compressive modulus of elasticity of the scaffold cartilage layer and the osteogenic layer were measured by scanning electron microscopy and microscopy CT. The osteochondral defect model on rabbit bi-lateral knees were established, and implanted with the non-CCL group (non-CCL scaffold compounding with ADSCs) and CCL group (CCL scaffold compounding with ADSCs). At 4, 8 and 12 weeks after implantation, the rabbits were euthanized, respectively.Gross observation score, histological and immunohistochemical assessment, biochemical quantitative of new osteochondral tissue, micro-CT scans for new bone, were executed. We evaluated the regeneration of osteochondral defects in each group, and verified the role of CCL in vivo. Results The biomimetic osteochondral scaffold with CCL had a consecutively overlapping trilayer struc-ture with different densities and pore structures, including a chondral layer (top layer), intermediate layer and bony layer (bottom layer). The cartilage layer had a well-oriented microporous structure with a uniform distribution with a pore size of (112.43±12.65) μm and a porosity of 90.25%±2.05%. The subchondral bone layer had a good three-dimensional macroporous structure, good con-nectivity, pore size (362.23±26.52) μm, porosity of osteogenic layer was 85.30%±1.80%. The cartilage regeneration in CCL+AD-SCs group was better than non-CCL+ADSCs group. The content of GAG and type II collagen in new cartilage tissue in CCL+AD-SCs group was much more than non-CCL+ADSCs group. The new bone tissue analysis and biomechanical testing had no signifi-cant differences between the two groups. Conclusion The biomimetic osteochondral SF/HA scaffold contained CCL mimics the structure of normal osteochondral tissue with good 3-dimensional pore structure and biocompatibility. The scaffold complex autolo-gous ADSCs successfully repair osteochondral defects in rabbit knee, and the presence of CCL accelerates the growth of cartilage. Key words: Tissue engineering; Cartilage; Tissue scaffolds; Slik; Hydroxyapatites

Treatment of Knee Osteochondritis Dissecans With a Cell-Free Biomimetic Osteochondral Scaffold: Clinical and Imaging Findings at Midterm Follow-up

Background: Osteochondritis dissecans (OCD) is a developmental condition of subchondral bone that may result in secondary separation and instability of the overlying articular cartilage, which in turn may lead to degeneration of the overall joint and early osteoarthritis. Biphasic scaffolds have been developed to address defects of the entire osteochondral unit by reproducing the different biological and functional requirements and guiding the growth of both bone and cartilage. Purpose: To evaluate midterm clinical and imaging results after cell-free osteochondral scaffold implantation for the treatment of knee OCD. Study Design: Case series; Level of evidence, 4. Methods: Twenty-seven patients (8 women, 19 men; mean age, 25.5 ± 7.7 years) were treated for knee OCD, with International Cartilage Repair Society (ICRS) grade 3 to 4 lesions with a mean size of 3.4 ± 2.2 cm2 (range, 1.5-12 cm2), and prospectively evaluated for up to 5 years using the ICRS classification system and the Tegner score. Eighteen patients underwent magnetic resonance imaging (MRI) at 24 and 60 months of follow-up, and the graft was evaluated using the magnetic resonance observation of cartilage repair tissue (MOCART) score for the cartilage layer, while a specific score was used for subchondral bone. Results: All patients significantly improved their clinical scores at each follow-up until their final evaluation. The mean International Knee Documentation Committee (IKDC) subjective score improved from 48.4 ± 17.8 to 82.2 ± 12.2 at 2 years (P < .0005), and it then remained stable for up to 5 years postoperatively (90.1 ± 12.0). The mean Tegner score increased from 2.4 ± 1.7 preoperatively to 4.4 ± 1.6 at 2 years (P = .001), with a further increase up to 5.0 ± 1.7 at 5 years of follow-up (P < .0005 vs preoperatively), reaching almost the preinjury level (5.7 ± 2.2). The MOCART score showed stable results between 24 and 60 months, whereas the subchondral bone status significantly improved over time. No correlation was found between MRI findings and clinical outcomes. Conclusion: This 1-step cell-free scaffold implantation procedure showed good and stable results for up to 60 months of follow-up for the treatment of knee OCD. MRI showed abnormalities, in particular at the subchondral bone level, but there was an overall improvement of features over time. No correlation was found between imaging and clinical findings.

MOCART Score is Not a Feasible Tool for the Assessment of Osteochondral Lesions of the Talus

Category: Ankle, Sports, Radiographic assessment Introduction/Purpose: To evaluate the applicability and reproducibility of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for morphological evaluation of osteochondral lesions of the talus (OLT) repaired using the autologous matrix-induced chondrogenesis (AMIC) technique. Methods: Two radiologists (R1-R2) and two orthopaedic surgeons (O1-O2) independently reviewed 26 MRI scans of the ankle performed on 13 patients (6 females, 7 males; age: 38.9±15.9, range 14-63) with OLT repaired using the AMIC technique between November 2011 and July 2015 at our institution. Out of 13, 7 were treated with biomimetic osteochondral scaffold implantation, while 6 were treated with bone-marrow derived cell transplantation. The MRI scans were performed at 6 and 12 months after treatment. For inter- and intra-observer agreement evaluation for each variable of the MOCART score we used Cohen’s kappa coefficient. Progression of MOCART score between 6 and 12 months evaluation was assessed using the Wilcoxon test. Results: The inter-observer agreement between R1-R2 ranged from poor (adhesions, k=0.124) to almost perfect (subchondral bone, k=0.866), while between O1-O2 ranged from absent (effusion, k=-0.190) to poor (surface, k=0.172). The intra-observer agreement of R1 ranged from poor (signal intensity, k=0.031) to substantial (subchondral lamina, k=0.677), while that of O1 ranged from absent (subchondral bone, k=-0.061) to substantial (surface, k=0.663). There was a statistically significant increase of MOCART score between 6-month and 12-month evaluation of R1 (Z=-2.672; P=0.008), R2 (Z=-2.721; P=0.007) and O1 (Z=- 3.034; P=0.002). Conversely, the increase of MOCART score between the 6-months and 12-months evaluation of O2 was not statistically significant (Z=-1.665; P=0.096). Conclusion: MRI certainly has a crucial role in the follow-up of surgical repaired OLT but the MOCART score does not seem to be sufficiently reliable and reproducible to be applied for this purpose.

Biomimetic design and fabrication of multilayered osteochondral scaffolds by low-temperature deposition manufacturing and thermal-induced phase-separation techniques

Integrative osteochondral repair is a useful strategy for cartilage-defect repair. To mimic the microenvironment, it is necessary that scaffolds effectively mimic the extracellular matrix of natural cartilage and subchondral bone. In this study, biomimetic osteochondral scaffolds containing an oriented cartilage layer, a compact layer, and a three-dimensional (3D)-printed core-sheath structured-bone layer were developed. The oriented cartilage layer was designed to mimic the structural and material characteristics of native cartilage tissue and was fabricated with cartilage matrix-chitosan materials, using thermal-induced phase-separation technology. The 3D-printed core-sheath structured-bone layer was fabricated with poly(L-lactide-co-glycolide)/β-tricalcium phosphate-collagen materials by low-temperature deposition technology, using a specially designed core-sheath nozzle, and was designed to mimic the mechanical characteristics of subchondral bone and improve scaffold hydrophilicity. The compact layer was designed to mimic the calcified-layer structure of natural cartilage to ensure the presence of different suitable microenvironments for the regeneration of bone and cartilage. A dissolving-bonding process was developed to effectively combine the three parts together, after which the bone and cartilage scaffolds exhibited good mechanical properties and hydrophilicity. Additionally, goat autologous bone mesenchymal stem cells (BMSCs) were isolated and then seeded into the bone and cartilage layers, respectively, and following a 1 week culture in vitro, the BMSC-scaffold constructs were implanted into a goat articular-defect model. Our results indicated that the scaffolds exhibited good biocompatibility, and 24 weeks after implantation, the femoral condyle surface was relatively flat and consisted of a large quantity of hyaloid cartilage. Furthermore, histological staining revealed regenerated trabecular bone formed in the subchondral bone-defect area. These results provided a new method to fabricate biomimetic osteochondral scaffolds and demonstrated their effectiveness for future clinical applications in cartilage-defect repair.

Can a biomimetic osteochondral scaffold be a reliable alternative to prosthetic surgery in treating late-stage SPONK?

BackgroundThis study aimed to assess the reliability of the Maioregen® biomimetic osteochondral scaffold (Finceramica Faenza SpA, Faenza, Italy) as a salvage and joint-preserving procedure in the treatment of late-stage osteonecrosis of the knee. MethodsEleven active patients aged under 65years and presenting with clinical and radiological signs of SPONK were treated with Maioregen®. All were clinically evaluated pre-operatively and yearly thereafter for a minimum of two years. Subjective IKDC and Lysholm Knee Scale scores were used to assess clinical outcome. A VAS scale served to quantify pre-operative pain and post-operative pain. Activity levels were evaluated pre-operatively and at follow-up using the Tegner Activity Scale. ResultsSubjective IKDC (40±15.0 to 65.7±14.8 (mean±SD)) and Lysholm Knee Scale (49.7±17.9 to 86.6±12.7 (mean±SD)) scores improved significantly from pre-operative evaluation (p<.01). VAS scores decreased from a pre-operative mean (±SD) of 6.3±2.5 to 1.6±2.7 at two years. The Tegner Activity Scale showed no significant differences between pre-injury and two-year follow-up.Two out of the 11 patients were symptomatic at 18months post implant and progressed to condylar collapse. These patients required total knee arthroplasty. ConclusionsUse of a biomimetic scaffold can be a valid option in the surgical treatment of SPONK in relatively young active patients. Indeed, this surgical technique, originally developed for osteochondritis dissecans, has been found to give good clinical results at medium-term follow-up of late-stage osteonecrosis treatment and could postpone or even avoid the need for joint replacement procedures.

Morphological characteristics of cartilage-bone transitional structures in the human knee joint and CAD design of an osteochondral scaffold.

BackgroundThere is a lack of understanding of the morphological characteristics of the cartilage-bone interface. Materials that are currently being used in tissue engineering do not adequately support the regeneration of bone and cartilage tissues. The present study aimed to explore the morphological characteristics of cartilage-bone transitional structures in the human knee joint and to design a biomimetic osteochondral scaffold based on morphological data.MethodsHistology, micro-computed tomography (micro-CT), and scanning electron microscopy (SEM) were used to investigate the microstructure of the cartilage-bone transitional structures. Morphological characteristics and their distribution were obtained and summarized into a biomimetic design. A three-dimensional model of a biomimetic osteochondral scaffold was CAD designed. A prototype of the resulting subchondral bone scaffold was constructed by stereolithography using resin.ResultsMicro-CT revealed that subchondral bone presented a gradually changing structure from the subchondral to spongy bone tissue. The subchondral bone plate was more compact with ~20 % porosity compared with ~60 % porosity for the spongy bone. Histology and SEM showed that cartilage was stabilized on the subchondral bone plate by conjunctions, imbedding, interlocking, and binding forces generated by collagen fibers. Some scattered defects allow blood vessel invasion and nutritional supply.ConclusionsThe subchondral bone plate is not an intact plate between the cartilage and bone cavity, and some scattered defects exist that allow blood vessel invasion and nutritional supply. This characteristic was used to design an osteochondral scaffold. This could be used to construct an osteochondral complex that is similar to native bones.

Trattamento dell’osteocondrite dissecante del ginocchio con scaffold osteocondrale biomimetico

The aim of this study was to evaluate the potential of a biomimetic osteochondral scaffold for the treatment of osteochondritis dissecans (OCD). Twenty-seven consecutive patients, affected by knee OCD, were treated with the implantation of an acellular collagen-hydroxyapatite scaffold and prospectively evaluated at 4 years of follow-up. A significant improvement in all clinical scores was obtained at up to the final follow-up. This osteochondral scaffold is a valid option for knee OCD, showing a good and durable clinical outcome even for the treatment of large lesions.

大尺寸关节支架的3D打印及应用

Implantation and long-term failure of artificial joints can cause unrecoverable tissue loss, whereas small-scale biodegradable osteochondral scaffolds can restore the mechanical environment and induce tissue regeneration within articular lesions, thus providing a new therapeutic strategy for repairing large-size defects. However, treatment development has been challenging because of the complex physical structure and mechanical environment of the lesions, and the demanding manufacturing techniques and surgical implantation strategies for multi-material composite scaffolds. This paper presents a novel multi-material osteochondral scaffold, and its bio-manufacturing technique and implantation. To induce tissue growth, PEG (polyethylene glycol), β -TCP ( β -tricalcium phosphate), and PLA (polylactide) biomaterials are selected to develop the new scaffolds. Based on limited radiological image data, techniques for reverse engineering, finite element analysis, and 3D printing are used to establish the cartilage lesion model in a sheep knee joint. Based on the mapping relationship between the scaffold physiological characteristics and joint defect mechanical properties, large-size biomimetic osteochondral scaffolds and their fixations are designed to fasten themselves securely to defects. Experiment results show that scaffold implantation restores the defects initial mechanical environment. Therefore, the proposed large-size osteochondral scaffolds through 3D printing technique is expected to provide a new treatment strategy for repairing large osteochondral defects.

Integrating biologically inspired nanomaterials and table-top stereolithography for 3D printed biomimetic osteochondral scaffolds.

The osteochondral interface of an arthritic joint is notoriously difficult to regenerate due to its extremely poor regenerative capacity and complex stratified architecture. Native osteochondral tissue extracellular matrix is composed of numerous nanoscale organic and inorganic constituents. Although various tissue engineering strategies exist in addressing osteochondral defects, limitations persist with regards to tissue scaffolding which exhibit biomimetic cues at the nano to micro scale. In an effort to address this, the current work focused on 3D printing biomimetic nanocomposite scaffolds for improved osteochondral tissue regeneration. For this purpose, two biologically-inspired nanomaterials have been synthesized consisting of (1) osteoconductive nanocrystalline hydroxyapatite (nHA) (primary inorganic component of bone) and (2) core-shell poly(lactic-co-glycolic) acid (PLGA) nanospheres encapsulated with chondrogenic transforming growth-factor β1 (TGF-β1) for sustained delivery. Then, a novel table-top stereolithography 3D printer and the nano-ink (i.e., nHA + nanosphere + hydrogel) were employed to fabricate a porous and highly interconnected osteochondral scaffold with hierarchical nano-to-micro structure and spatiotemporal bioactive factor gradients. Our results showed that human bone marrow-derived mesenchymal stem cell adhesion, proliferation, and osteochondral differentiation were greatly improved in the biomimetic graded 3D printed osteochondral construct in vitro. The current work served to illustrate the efficacy of the nano-ink and current 3D printing technology for efficient fabrication of a novel nanocomposite hydrogel scaffold. In addition, tissue-specific growth factors illustrated a synergistic effect leading to increased cell adhesion and directed stem cell differentiation.