Background Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee. Methods The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site. Results Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and s...

Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation

Tissue engineering can be used to restore, maintain, or enhance tissues and organs. The potential impact of this field, however, is far broader-in the future, engineered tissues could reduce the need for organ replacement, and could greatly accelerate the development of new drugs that may cure patients, eliminating the need for organ transplants altogether.

https://science.sciencemag.org/content/sci/295/5557/1009.full.pdf

Tissue Engineering--Current Challenges and Expanding Opportunities

Muscle dysfunction and associated mobility impairment, common among the frail elderly, increase the risk of falls, fractures, and functional dependency. We sought to characterize the muscle weakness of the very old and its reversibility through strength training. Ten frail, institutionalized volunteers aged 90 ± 1 years undertook 8 weeks of high-intensity resistance training. Initially, quadriceps strength was correlated negatively with walking time (r= -.745). Fat-free mass (r=.732) and regional muscle mass (r=.752) were correlated positively with muscle strength. Strength gains averaged 174% ±31% (mean ± SEM) in the 9 subjects who completed training. Midthigh muscle area increased 9.0%± 4.5%. Mean tandem gait speed improved 48% after training. We conclude that high-resistance weight training leads to significant gains in muscle strength, size, and functional mobility among frail residents of nursing homes up to 96 years of age. (JAMA. 1990;263:3029-3034)

https://jamanetwork.com/journals/JAMA/articlepdf/382128/jama_263_22_029.pdf

High-Intensity Strength Training in Nonagenarians: Effects on Skeletal Muscle

The objectives of this study are to review the long-term consequences of injuries to the anterior cruciate ligament and menisci, the pathogenic mechanisms, and the causes of the considerable variability in outcome. Injuries of the anterior cruciate ligament and menisci are common in both athletes and the general population. At 10 to 20 years after the diagnosis, on average, 50% of those with a diagnosed anterior cruciate ligament or meniscus tear have osteoarthritis with associated pain and functional impairment: the young patient with an old knee. These individuals make up a substantial proportion of the overall osteoarthritis population. There is a lack of evidence to support a protective role of repair or reconstructive surgery of the anterior cruciate ligament or meniscus against osteoarthritis development. A consistent finding in a review of the literature is the often poor reporting of critical study variables, precluding data pooling or a meta-analysis. Osteoarthritis development in the injured joints is caused by intra-articular pathogenic processes initiated at the time of injury, combined with long-term changes in dynamic joint loading. Variation in outcome is reinforced by additional variables associated with the individual such as age, sex, genetics, obesity, muscle strength, activity, and reinjury. A better understanding of these variables may improve future prevention and treatment strategies. In evaluating medical treatment, we now expect large randomized clinical trials complemented by postmarketing monitoring. We should strive toward a comparable level of quality of evidence in surgical treatment of knee injuries. In instances in which a randomized clinical trial is not feasible, natural history and other observational cohort studies need to be as carefully designed and reported as the classic randomized clinical trial, to yield useful information.

/pdf/the-long-term-consequence-of-anterior-cruciate-ligament-and-3mhkqdkmu4.pdf

The Long-term Consequence of Anterior Cruciate Ligament and Meniscus Injuries Osteoarthritis

https://www.oarsijournal.com/article/S1063-4584(02)90801-0/pdf

Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects.

Autologous cultured chondrocyte transplantation was introduced in Sweden in 1987 for the treatment of large (1.5-12.0 cm2) full thickness chondral defects of the knee. The clinical, arthroscopic, and histologic results from the first 101 patients treated using this technique are reported in this study. Patients were assessed retrospectively using three types of endpoints: patient and physician derived clinical rating scales (five validated and two new); arthroscopic assessment of cartilage fill, integration, and surface hardness; and standard histochemical techniques. Ninety-four patients with 2- to 9-years followup were evaluable. Good to excellent clinical results were seen in individual groups as follows: isolated femoral condyle (92%), multiple lesions (67%), osteochondritis dissecans (89%), patella (65%), and femoral condyle with anterior cruciate ligament repair (75%). Arthroscopic findings in 53 evaluated patients showed good repair tissue fill, good adherence to underlying bone, seamless integration with adjacent cartilage, and hardness close to that of the adjacent tissue. Hypertrophic response of the periosteum or graft or both was identified in 26 arthroscopies; seven were symptomatic and resolved after arthroscopic trimming. Graft failure occurred in seven (four of the first 23 and three of the next 78) patients. Histologic analysis of 37 biopsy specimens showed a correlation between hyalinelike tissue (hyaline matrix staining positive for Type II collagen and lacking a fibrous component) and good to excellent clinical results. The good clinical outcomes of autologous chondrocyte transplantation in this study are encouraging, and clinical trials are being done to assess the outcomes versus traditional fibrocartilage repair techniques.

Two- to 9-year outcome after autologous chondrocyte transplantation of the knee.

We evaluated the durability of autologous chondrocyte transplantation grafts in 61 patients treated for isolated cartilage defects on the femoral condyle or the patella and followed up for a mean of 7.4 years (range, 5 to 11). Durability was determined by comparing the clinical status at the long-term follow-up with that found 2 years after the transplantation. After 2 years, 50 of the 61 patients had good or excellent clinical results, and 51 of 61 had good or excellent results at 5 to 11 years later. Grafted areas from 11 of the patients were evaluated with an electromechanical indentation probe during a second-look arthroscopy procedure (mean follow-up, 54.3 months; range, 33 to 84); stiffness measurements were 90% or more of those of normal cartilage in eight patients. Eight of twelve 2-mm biopsy samples taken from these patients showed hyaline characteristics with safranin O staining and a homogeneous appearance in polarized light. Three fibrous and eight hyaline biopsy specimens stained positive to aggrecan and to cartilage oligomeric matrix protein. Hyaline-like specimens stained positive for type II collagen, and fibrous, for type I collagen. Autologous chondrocyte transplantation for the treatment of articular cartilage injuries has a durable outcome for as long as 11 years.

Autologous Chondrocyte Transplantation Biomechanics and Long-Term Durability

The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation.

Background: The medium-term results of autologous chondrocyte implantation (ACI) have shown good to excellent outcomes for the majority of patients. However, no long-term results 10 to 20 years after the surgery have been reported.Hypothesis: Autologous chondrocyte implantation provides a durable solution to the treatment of full-thickness cartilage lesions of the knee, maintaining good clinical results even 10 to 20 years after implantation.Study Design: Case series; Level of evidence, 4.Methods: In this uncontrolled study, questionnaires with the Lysholm, Tegner-Wallgren, Brittberg-Peterson, modified Cincinnati (Noyes), and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores were sent to 341 patients. Preoperative Lysholm, Tegner-Wallgren, and Brittberg-Peterson scores were also retrieved when possible from patients’ files. The patients were asked to grade their status during the past 10 years as better, worse, or unchanged. Finally, they were asked if they would do the operation again.Results: T...

Lars Peterson

Papers

Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation

Two- to 9-year outcome after autologous chondrocyte transplantation of the knee.

Autologous Chondrocyte Transplantation Biomechanics and Long-Term Durability

The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation.

Autologous Chondrocyte Implantation A Long-term Follow-up