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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 67 - 67
1 Dec 2021
Walter N Rupp M Hierl K Koch M Kerschbaum M Worlicek M Alt V
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Aim

We aimed to evaluate the impact of knee periprosthetic joint infection (PJI) by assessing the patients’ long-term quality of life and explicitly their psychological wellbeing after successful treatment.

Method

Thirty-six patients with achieved eradication of infection after knee PJI were included. Quality of life was evaluated with the EQ-5D and SF-36 outcome instruments as well as with an ICD-10 based symptom rating (ISR) and compared to normative data.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 18 - 18
1 Jul 2020
Pattappa G Koch M Weber J Lang S Bohrer A Johnstone B Docheva D Zellner J Angele P Krueckel J Franke D
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Osteoarthritis (OA) is one of the most prevalent joint diseases involving progressive and degenerative changes to cartilage resulting from a variety of etiologies including post-traumatic incident or aging. OA lesions can be treated at its early stages through cell-based tissue engineering therapies using Mesenchymal Stem Cells (MSCs). In vivo models for evaluating these strategies, have described both chondral (impaction) and osteochondral (biopsy punch) defects. The aim of the investigation was to develop a compact and reproducible defect inducing post-traumatic degenerative changes mimicking early OA. Additionally, a pilot study to evaluate the efficacy of MSC-hydrogel treatment was also assessed.

Surgery was performed on New Zealand white rabbits (male, 5–8 months old) with defects created on medial femoral condyle. For developing an appropriate defect, three approaches were used for evaluation: a biopsy punch (n = three at six and twelve weeks), an impaction device1 (n = three at six and twelve weeks) and a dental drill model (n = six at six and twelve weeks). At stated time points, condyles were harvested and decalcified in 10% EDTA, then embedded in Tissue-Tek and sectioned using a cryostat. Upon identification of region of interest, sections were stained with Safranin-O/Fast green and scored using OARSI scoring system by two blinded observers2. For the pilot study, autologous bone marrow was harvested from rabbits and used to isolate and expand MSCs. The Dental drill model was applied to both knee condyles, left untreated for six weeks at which stage, PKH26 fluorescently labelled MSCs were seeded into a hyaluronic acid hydrogel (TETEC). Repair tissue was removed from both condyles and MSC-hydrogel was injected into the left knee, whilst right knee was left empty. Rabbits were sacrificed at one (n = 1), six (n = 3) and twelve (n = 3) weeks post-treatment, processed as previously described and cartilage regeneration evaluated using Sellers score3.

Impacted condyles exhibited no observed changes histologically (Mean OARSI score = 1 + 1), whereas biopsy punched and dental drilled defects demonstrated equal signs of cartilage erosion (OARSI score = 3 + 1) at assessed time points. However, biopsy punched condyles formed a diffusive defect, whereas dental drilled condyles showed a more defined, compact and reproducible defect. In the pilot study, PKH-labelled MSCs were observed at one and six weeks post-implantation within the defect space where hydrogel was injected. Tissue regeneration assessment indicated no difference between empty (Mean Sellers score = 14 + 2) and MSC treated defects (Sellers score = 16 + 5) at six weeks post-injection. At twelve weeks, MSC treated defects showed improved tissue regeneration with substantial subchondral bone restoration and good integration of regenerative cartilage with surrounding intact tissue (Sellers score = 10 + 1), whereas untreated defects showed no change in regeneration compared to six weeks (Sellers score = 16 + 2).

Dental drill model was found to be the appropriate strategy for investigating early OA progression and treatment. Application of MSCs in defects showed good cartilage regeneration after twelve weeks application, indicating their promise in the treatment of early OA defects.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 68 - 68
1 Apr 2018
Riedl M Koch M Freimoser F Pattappa G Zellner J Docheva D Angele P Pfeifer C
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Introduction

Human Mesenchymal stem cells (hMSCs) are a promising source for articular cartilage repair. Unfortunately, under in vitro conditions, chondrogenically differentiated hMSCs have the tendency to undergo hypertrophy similar to growth plate chondrocytes. Retinoic acid (RA) signalling plays a key role in growth plate hypertrophy. Whilst RA agonists block chondrogenesis and foster hypertrophy during later stages, RAR inverse agonists (IA) enhance chondrogenesis when applied early in culture. Therefore, we hypothesized that treatment with RAR IA will attenuate hypertrophy in chondrogenically differentiated hMSCs. To test this hypothesis, we analysed early (initial chondrogenic differentiation) and late treatment (hypertrophy stage) of hMSCs with an RAR IA.

Methods

Pellets of passage 2 hMSCs were formed in V-bottom well plates by centrifugation and pre-differentiated in a chemically defined medium containing 10ng/mL TGFß (CM+) for 14 days. Thereafter, pellets were cultured for an additional 14 days under 6 conditions: CM+, CM- (w/out TGFß), and hypertrophic medium (CM- with 25 ng/ml BMP 4, w/out dexamethasone). Each of these first three conditions was additionally supplemented with the RA receptor (RAR) inverse agonist BMS493 (BMS) at 2μM after 14 days of chondrogenic pre-differentiation. One additional BMP4 group was supplemented with BMS from the beginning of chondrogenic differentiation until day 14. The pellets were assessed for gene expression (Col 2, Col 10, Col 1 and MMP13) and histologically using dimethyl methylene blue (DMMB), alkaline phosphatase staining (ALP) and collagen II and X immunohistochemistry.


The Journal of Bone & Joint Surgery British Volume
Vol. 56-B, Issue 1 | Pages 62 - 68
1 Feb 1974
Robichon J Desjardins JP Koch M Hooper CE

1. Experimental work with piglets supports the theory that diminished blood supply to the femoral head not only causes necrosis of the epiphysis but also a decrease in cartilage cell production in the germinal layer of the epiphysial plate, thus causing decreased longitudinal bone growth. Appositional growth continues in the metaphysis because its blood supply remains intact or, at least, is less impaired. The resulting disturbance of the normal remodelling must lead to a short wide neck such as occurs in Legg-Perthes' disease.

2. Measurements were made of the length and width of the femoral neck on radiographs of forty patients with Legg-Perthes' disease. The results showed that the degree of shortening and widening is related to the extent of structural change in the head.

3. Repeated measurements in the early stages of the active disease may permit an early prognosis which may be of great assistance in selecting the treatment suitable to each patient. The financial assistance of the Ontario Society for Crippled Children is gratefully acknowledged.