The Effect of the Repair of Induced Articular Cartilage Defects in Pigs Using Calcium Phosphate Cement with Aminoacids on the Concentrations of Selected Inflammatory Markers and Serum Enzyme Activities

The repair of articular cartilage defects is an intensively developing area of research. Severe inflammatory reactions after surgical interventions on bones or their structures may lead to changes of bone or joint asymmetry. In laboratory diagnostics, some inflammatory biomarkers and serum enzymes are available for the evaluation of these inflammatory processes. A general understanding of inflammatory responses following the repair of cartilage defects is still lacking. The aim of this study was to describe the alterations in the values of five inflammatory markers and the activities of several enzymes in seven 5-month-old pigs within the first 30 days following the restoration of induced articular cartilage defects using the tetracalcium phosphate/nanomoneite cement powder enriched with amino acids (CAL). The reconstruction of surgically induced defects was accompanied by a significant increase of serum amyloid A (SAA, p < 0.05), haptoglobin (Hp, p < 0.001), C-reactive protein (CRP, p < 0.01), and pig major acute phase protein (pig-MAP, p < 0.001). Their concentrations decreased gradually within one-month post-surgery, the values recorded at the end of this period were higher than those obtained prior to surgery. The concentrations of α1-acid glycoprotein (AGP) showed no significant changes during the evaluated period. Alterations were also found in the enzyme activities of creatine kinase (p < 0.05), lactate-dehydrogenase and alkaline phosphatase (p < 0.01). These findings suggest that SAA, Hp, CRP and pig-MAP might be applicable biomarkers of acute phase response for the monitoring of postoperative period.

The use of a novel deer antler decellularized cartilage-derived matrix scaffold for repair of osteochondral defects

Background The physiologic regenerative capacity of cartilage is severely limited. Current studies on the repair of osteochondral defects (OCDs) have mainly focused on the regeneration of cartilage tissues. The antler cartilage is a unique regenerative cartilage that has the potential for cartilage repair. Methods Antler decellularized cartilage-derived matrix scaffolds (adCDMs) were prepared by combining freezing-thawing and enzymatic degradation. Their DNA, glycosaminoglycans (GAGs), and collagen content were then detected. Biosafety and biocompatibility were evaluated by pyrogen detection, hemolysis analysis, cytotoxicity evaluation, and subcutaneous implantation experiments. adCDMs were implanted into rabbit articular cartilage defects for 2 months to evaluate their therapeutic effects. Results AdCDMs were observed to be rich in collagen and GAGs and devoid of cells. AdCDMs were also determined to have good biosafety and biocompatibility. Both four- and eight-week treatments of OCDs showed a flat and smooth surface of the healing cartilage at the adCDMs filled site. The international cartilage repair society scores (ICRS) of adCDMs were significantly higher than those of controls (porcine dCDMs and normal saline) (p < 0.05). The repaired tissue in the adCDM group was fibrotic with high collagen, specifically, type II collagen. Conclusions We concluded that adCDMs could achieve excellent cartilage regeneration repair in a rabbit knee OCDs model. Our study stresses the importance and benefits of adCDMs in bone formation and overall anatomical reconstitution, and it provides a novel source for developing cartilage-regenerating repair materials.

Engineering large, anatomically shaped osteochondral constructs with robust interfacial shear properties

Despite the prevalence of large (>5 cm2) articular cartilage defects involving underlying bone, current tissue-engineered therapies only address small defects. Tissue-engineered, anatomically shaped, native-like implants may address the need for off-the-shelf, tissue-repairing therapies for large cartilage lesions. This study fabricated an osteochondral construct of translationally relevant geometry with robust functional properties. Scaffold-free, self-assembled neocartilage served as the chondral phase, and porous hydroxyapatite served as the osseous phase of the osteochondral constructs. Constructs in the shape and size of an ovine femoral condyle (31 × 14 mm) were assembled at day 4 (early) or day 10 (late) of neocartilage maturation. Early osteochondral assembly increased the interfacial interdigitation depth by 244%, interdigitation frequency by 438%, interfacial shear modulus by 243-fold, and ultimate interfacial shear strength by 4.9-fold, compared to late assembly. Toward the development of a bioprosthesis for the repair of cartilage lesions encompassing up to an entire condylar surface, this study generated a large, anatomically shaped osteochondral construct with robust interfacial mechanical properties and native-like neocartilage interdigitation.

Maturation process of regenerated tissues after single-stage simultaneous autologous particulated cartilage implantation and open wedge high tibial osteotomy for articular cartilage defects with medial osteoarthritis of bilateral knees: a case report

Background Open wedge high tibial osteotomy (OWHTO) is an effective treatment option for young and middle-aged active patients with medial unicompartmental knee osteoarthritis (OA). In addition, particulated cartilage implantation has been developed as a simple procedure for cartilage regeneration. Thus, to improve the OWHTO outcomes, a single-stage, simultaneous bilateral knee arthroscopic particulated cartilage implantation with OWHTO was performed. Case presentation A 60-year-old male patient presented with severe bilateral knee pain, with grade 2 varus knee OA of the Kellgren–Lawrence classification. Primary arthroscopic evaluations based on the International Cartilage Repair Society grading system showed grade 3c articular cartilage defects of 1.5 cm in diameter at the center of the bilateral medial femoral condyles. Following bilateral OWHTO, the healthy cartilage tissue was harvested from the lateral wall of the unilateral femoral intercondylar notch and minced with the cartilage processor. Then, subchondral drillings and cartilage fragment implantations into the bilateral defects were performed arthroscopically. One year postsurgery, second-look arthroscopy findings revealed that the defects were filled with cartilage-like tissues. The maturation process of the regenerated tissues was confirmed with T2 mapping magnetic resonance imaging during the 3-year follow-up period. The patient could walk without a cane, and all Knee Injury and Osteoarthritis Outcome Score parameters were improved without any correction loss in 3 years. Conclusions This is the first report to evaluate the maturation process of the implanted particulated cartilage tissue with T2 mapping magnetic resonance imaging for 3 years. The effect of chondral resurfacing procedure with OWHTO remains unclear; however, the implantation of arthroscopic particulated cartilage fragments is a single-stage and less-invasive procedure. This treatment could regenerate cartilage-like tissue in the present case. Therefore, this additional procedure could potentially improve the long-term outcomes of OWHTO.

Polycaprolactone Based Biomaterials and Sodium Hyaluronate Nanoreservoirs for Cartilage Regeneration

Obstacles persist in the treatment and prevention of articular cartilage defects. Polycaprolactone (PCL) and poly(vinyl-pyrrolidone) (PVP) biomaterials were obtained by electrospinning and electrospraying to inspect their potential application for cartilage regeneration. Sodium hyaluronate (SH) was then added into nanofibers of PCL and particles of PVP. The aim of incorporating sodium hyaluronate to this polymer is to enhance the capacity of articular cartilage to regenerate. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) were seeded onto these tissue engineering (TE) products. The cell viability in vitro and the ability of biomaterials to support the chondrogenic differentiation of hBM-MSCs have been assessed. We report here that hBM-MSCs on these biomaterials were not able to regenerate articular cartilage mainly due to unsuitable culture environment.

The Fragility of Statistical Significance in Cartilage Restoration of the Knee: A Systematic Review of Randomized Controlled Trials

Objective The purpose of this study was to utilize fragility analysis to assess the robustness of randomized controlled trials (RCTs) evaluating the management of articular cartilage defects of the knee. We hypothesize that the cartilage restorative literature will be fragile with the reversal of only a few outcome events required to change statistical significance. Design RCTs from 11 orthopedic journals indexed on PubMed from 2000 to 2020 reporting dichotomous outcome measures relating to the management of articular cartilage defects of the knee were included. The Fragility Index (FI) for each outcome was calculated through the iterative reversal of a single outcome event until significance was reversed. The Fragility Quotient (FQ) was calculated by dividing each FI by study sample size. Additional statistical analysis was performed to provide median FI and FQ across subgroups. Results Nineteen RCTs containing 60 dichotomous outcomes were included for analysis. The FI and FQ of all outcomes was 4 (IQR 2-7) and 0.067 (IQR 0.034-0.096), respectively. The average number of patients lost to follow-up (LTF) was 3.9 patients with 15.8% of the included studies reporting LTF greater than or equal to 4, the FI of all included outcomes. Conclusions The orthopedic literature evaluating articular cartilage defects of the knee is fragile as the reversal of relatively few outcome events may alter the significance of statistical findings. We therefore recommend comprehensive fragility analysis and triple reporting of the P value, FI, and FQ to aid in the interpretation and contextualization of clinical findings reported in the cartilage restoration literature.