Outcomes of Bulk Fresh Osteochondral Allografts for Cartilage Restoration in the Knee

Osteoarthritis is a major concern in the United States and worldwide. Current non-surgical and surgical approaches alleviate pain but show little evidence of cartilage restoration. Cell-based treatments may hold promise for the regeneration of hyaline cartilage-like tissue at the site of injury or wear. Cell–cell and cell–matrix interactions have been shown to drive cell differentiation pathways. Biomaterials for clinically relevant applications can be generated from decellularized porcine auricular cartilage. This material may represent a suitable scaffold on which to seed and grow chondrocytes to create new cartilage. In this study, we used decellularization techniques to create an extracellular matrix scaffold that supports chondrocyte cell attachment and growth in tissue culture conditions. Results presented here evaluate the decellularization process histologically and molecularly. We identified new and novel biomarker profiles that may aid future cartilage decellularization efforts. Additionally, the resulting scaffold was characterized using scanning electron microscopy, fluorescence microscopy, and proteomics. Cellular response to the decellularized scaffold was evaluated by quantitative real-time PCR for gene expression analysis.

Download Full-text

Overlapping Allografts Provide Superior and More Reliable Surface Topography Matching Than Oblong Allografts: A Computer-Simulated Model Study

The American Journal of Sports Medicine ◽

10.1177/03635465211003074 ◽

2021 ◽

pp. 036354652110030

Author(s):

Hailey P. Huddleston ◽

Atsushi Urita ◽

William M. Cregar ◽

Theodore M. Wolfson ◽

Brian J. Cole ◽

...

Keyword(s):

Articular Cartilage ◽

Surface Topography ◽

Osteochondral Allograft ◽

Cartilage Defects ◽

Radius Of Curvature ◽

Cartilage Surface ◽

3 Dimensional ◽

Cloud Models ◽

And Cartilage ◽

Osteochondral Allografts

Background: Osteochondral allograft transplantation is 1 treatment option for focal articular cartilage defects of the knee. Large irregular defects, which can be treated using an oblong allograft or multiple overlapping allografts, increase the procedure’s technical complexity and may provide suboptimal cartilage and subchondral surface matching between donor grafts and recipient sites. Purpose: To quantify and compare cartilage and subchondral surface topography mismatch and cartilage step-off for oblong and overlapping allografts using a 3-dimensional simulation model. Study Design: Controlled laboratory study. Methods: Human cadaveric medial femoral hemicondyles (n = 12) underwent computed tomography and were segmented into cartilage and bone components using 3-dimensional reconstruction and modeling software. Segments were then exported into point-cloud models. Modeled defect sizes of 17 × 30 mm were created on each recipient hemicondyle. There were 2 types of donor allografts from each condyle utilized: overlapping and oblong. Grafts were virtually harvested and implanted to optimally align with the defect to provide minimal cartilage surface topography mismatch. Least mean squares distances were used to measure cartilage and subchondral surface topography mismatch and cartilage step-off. Results: Cartilage and subchondral topography mismatch for the overlapping allograft group was 0.27 ± 0.02 mm and 0.80 ± 0.19 mm, respectively. In comparison, the oblong allograft group had significantly increased cartilage (0.62 ± 0.43 mm; P < .001) and subchondral (1.49 ± 1.10 mm; P < .001) mismatch. Cartilage step-off was also found to be significantly increased in the oblong group compared with the overlapping group ( P < .001). In addition, overlapping allografts more reliably provided a significantly higher percentage of clinically acceptable (0.5- and 1-mm thresholds) cartilage surface topography matching (overlapping: 100% for both 0.5 and 1 mm; oblong: 90% for 1 mm and 56% for 0.5 mm; P < .001) and cartilage step-off (overlapping: 100% for both 0.5 and 1 mm; oblong: 86% for 1 mm and 12% for 0.5 mm; P < .001). Conclusion: This computer simulation study demonstrated improved topography matching and decreased cartilage step-off with overlapping osteochondral allografts compared with oblong osteochondral allografts when using grafts from donors that were not matched to the recipient condyle by size or radius of curvature. These findings suggest that overlapping allografts may be superior in treating large, irregular osteochondral defects involving the femoral condyles with regard to technique. Clinical Relevance: This study suggests that overlapping allografts may provide superior articular cartilage surface topography matching compared with oblong allografts and do so in a more reliable fashion. Surgeons may consider overlapping allografts over oblong allografts because of the increased ease of topography matching during placement.

Download Full-text

Allogeneic Umbilical Cord Blood–Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967120973052 ◽

2021 ◽

Vol 9 (1) ◽

pp. 232596712097305

Author(s):

Hong-Chul Lim ◽

Yong-Beom Park ◽

Chul-Won Ha ◽

Brian J. Cole ◽

Beom-Koo Lee ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Cartilage Repair ◽

Older Patients ◽

Cartilage Defects ◽

Full Thickness ◽

Phase 3 ◽

Randomized Controlled ◽

Cartilage Restoration

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group ( P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group ( P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group ( P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up ( P < .05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

Download Full-text

Articular Cartilage Restoration Requires Cells, Scaffolds, Growth Factors, and Mechanical Stimulation

Arthroscopy The Journal of Arthroscopic and Related Surgery ◽

10.1016/j.arthro.2021.03.014 ◽

2021 ◽

Vol 37 (5) ◽

pp. 1359-1360

Author(s):

Mark G. Siegel ◽

James H. Lubowitz ◽

Jefferson C. Brand ◽

Michael J. Rossi

Keyword(s):

Growth Factors ◽

Articular Cartilage ◽

Mechanical Stimulation ◽

Cartilage Restoration

Download Full-text

Concomitant Osteotomy Reduces Risk of Reoperation Following Cartilage Restoration Procedures of the Knee: A Matched Cohort Analysis

Cartilage ◽

10.1177/19476035211011515 ◽

2021 ◽

pp. 194760352110115

Author(s):

Jacob G. Calcei ◽

Kunal Varshneya ◽

Kyle R. Sochacki ◽

Marc R. Safran ◽

Geoffrey D. Abrams ◽

...

Keyword(s):

Cohort Analysis ◽

Reoperation Rate ◽

Similar Rate ◽

Osteochondral Allograft ◽

Complication Rates ◽

Cartilage Restoration ◽

Chondrocyte Implantation ◽

The Cost ◽

Reoperation Rates

Objective The objective of this study is to compare the (1) reoperation rates, (2) 30-day complication rates, and (3) cost differences between patients undergoing isolated autologous chondrocyte implantation (ACI) or osteochondral allograft transplantation (OCA) procedures alone versus patients with concomitant osteotomy. Study Design Retrospective cohort study, level III. Design Patients who underwent knee ACI (Current Procedural Terminology [CPT] 27412) or OCA (CPT 27415) with minimum 2-year follow-up were queried from a national insurance database. Resulting cohorts of patients that underwent ACI and OCA were then divided into patients who underwent isolated cartilage restoration procedure and patients who underwent concomitant osteotomy (CPT 27457, 27450, 27418). Reoperation was defined by ipsilateral knee procedure after the index surgery. The 30-day postoperative complication rates were assessed using ICD-9-CM codes. The cost per patient was calculated. Results A total of 1,113 patients (402 ACI, 67 ACI + osteotomy, 552 OCA, 92 OCA + osteotomy) were included (mean follow-up of 39.0 months). Reoperation rate was significantly higher after isolated ACI or OCA compared to ACI or OCA plus concomitant osteotomy (ACI 68.7% vs. ACI + osteotomy 23.9%; OCA 34.8% vs. OCA + osteotomy 16.3%). Overall complication rates were similar between isolated ACI (3.0%) and ACI + osteotomy (4.5%) groups and OCA (2.5%) and OCA + osteotomy (3.3%) groups. Payments were significantly higher in the osteotomy groups at day of surgery and 9 months compared to isolated ACI or OCA, but costs were similar by 2 years postoperatively. Conclusions Concomitant osteotomy at the time of index ACI or OCA procedure significantly reduces the risk of reoperation with a similar rate of complications and similar overall costs compared with isolated ACI or OCA.

Download Full-text

EPIDEMIOLOGY OF PEDIATRIC CARTILAGE RESTORATION PROCEDURES IN THE UNITED STATES: INSURANCE AND GEOGRAPHY PLAY A ROLE

Orthopaedic Journal of Sports Medicine ◽

10.1177/2325967120s00248 ◽

2020 ◽

Vol 8 (4_suppl3) ◽

pp. 2325967120S0024

Author(s):

Tyler B. Hall ◽

Max J. Hyman ◽

Neeraj M. Patel

Keyword(s):

United States ◽

Children And Adolescents ◽

Statistical Significance ◽

Private Insurance ◽

Univariate Analysis ◽

The United States ◽

National Database ◽

The West ◽

Cartilage Restoration ◽

Common Diagnosis

Background: A number of surgical options are available for sizeable articular cartilage lesions of the knee. These include osteochondral autograft (OAU) or allograft (OAL) transfer, or autologous chondrocyte implantation (ACI). In the pediatric population, there is little data on the patients undergoing these procedures or evidence to support one technique over another, which may lead to variation in preferred practice. Hypothesis/Purpose: The purpose of this study is to analyze the epidemiology of children and adolescents undergoing OAU, OAL, and ACI in the United States, with attention to variation along the lines of demographic and geographic factors. Methods: The Pediatric Health Information System, a national database consisting of 49 children’s hospitals, was queried for all patients undergoing OAU, OAL, and ACI between 2012 and 2018. Demographic information was collected for each subject. United States Census guidelines were used to categorize hospitals geographically into regions. Univariate analysis was followed by purposeful entry multivariate regression to adjust for confounding factors. Results: A total of 809 subjects with a mean age of 15.4±2.4 years were included in the analysis. Of these, 393 (48.6%) underwent OAL, 339 (41.9%) underwent OAU, and 77 (9.5%) underwent ACI. The most common diagnosis at the time of surgery was osteochondritis dissecans in 360 patients (44.5%) followed by an associated cruciate ligament injury in 126 (15.6%) and patellar instability in 98 (12.1%). After adjusting for confounders in a multivariate model, ACI was more 3.4 times more likely to be performed in patients with private insurance than those that were publicly insured (95% CI 1.5-7.5, p=0.002). Furthermore, a patient in this Northeast was 29.3 times more likely to undergo ACI than in the West (95% CI 4.0-217.4, p=0.001). OAU was performed most frequently in the West and Midwest (52.4% and 51.8% of the time, respectively; p<0.001). Univariate analysis also revealed differences along the lines of race, but these findings did not maintain statistical significance in multivariate analysis. Conclusion: In the United States, there is substantial variation in the procedures performed for cartilage restoration in children and adolescents. Though ACI is the least commonly selected operation overall, it is significantly more likely to be performed on patients with private insurance and those in the Northeast. OAU is the most commonly performed procedure in the West and Midwest.

Download Full-text