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A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects.

ABSTRACT: Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide-co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.

SUBMITTER: Kleinhans C

PROVIDER: S-EPMC4744951 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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Project description:Background:The treatment of fracture- or non-union-related infections has persistently been a major challenge for both patients and treating surgeons. With rising aging of patients and increasing comorbidities, combined with the heterogeneity of germs and any number of multi-resistance against standard antibiotics, a successful treatment is increasingly difficult. One potential solution could be a custom-made individualized antibacterial coating of standard implants with a biphasic degradable biocarrier (Cerament G/V, supplied by Bonesupport AB, Lund, Sweden) that releases high doses of antibiotics around the bone-implant-interface. Here, we describe our technique of coating intramedullary nails, plates and press-fit shoulder endoprostheses which may prevent bacterial adhesion and biofilm formation. So far, there is very limited experience in individual coating of implants in hip or knee endoprostheses to prevent reoccurrence of surgical-site infection. Currently, no reports are available for coating of stems of shoulder prosthesis and nails or plates for fracture fixation. Methods:Here, we show our first experiences with a new individualized surgical technique of coating these implants with a resorbable antibiotic-loaded hydroxyapatite/calcium sulphate biocomposite to prevent biofilm formation and thereby recurrence of bone or joint infection. We describe three cases for coating of plates and nails for fracture fixation and coating of stems of a shoulder prosthesis. Results:No adverse events of the resorbable bone graft substitute were observed. In all of the cases, no recurrence of the infection was observed and osseointegration was achieved. After implant coating of the shoulder prosthesis, no radiological signs of loosening were detected. Conclusion:We present a new surgical approach of a surface coating of plates, intramedullary nails or prostheses. The osteoconductive- and anti-inflammatory effect of the gentamicin- or vancomycin-loaded hydroxyapatite/calcium sulphate bone graft substitutes shows promising results.

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A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects.

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