Ulla Stumpf

Selection of proangiogenic ascorbate derivatives and their exploitation in a novel drug‐releasing system for wound healing

The pathophysiology leading to delayed wound healing is complex and efficient therapeutic approaches for accelerated wound healing currently do not exist. We developed a novel drug‐eluting platform for the potential use in wound dressings. Here, we report on the potential of eluting ascorbic acid‐2‐phosphate (ASC‐2P), a highly stable variant of ascorbic acid, to induce angiogenesis and to promote collagen synthesis by fibroblasts. The drug‐eluting platform device (DEPD) consists of biocompatible polymeric layers comprising polyethylene terephtalate, polyvinyl alcohol (PVA), and polyurethane with PVA as the solvent for ASC‐2P. The angiogenic potential of ASC‐2P was evaluated in the endothelial cell tube formation assay (TFA) and in the chorion allantoic membrane (CAM) model. Collagen synthesis by ASC‐2P‐stimulated fibroblasts was determined by Sirius Red staining. ASC‐2P significantly induced angiogenesis in five independent TFA and CAM assays and induced collagen synthesis in two different fibroblast cell lines. The eluting kinetics of ASC‐2P was determined by the ultraviolet NanoDrop method and the functional 2,2′‐Azinobis‐(3‐ethylbenzthiazolin‐6‐sulfonic acid) method. Eluting profiles showed a continuous release in the range of biologically effective concentrations >10 days. This is the first report showing the proangiogenic‐ and collagen‐promoting features of ASC‐2P. DEPD loaded with ASC‐2P ought to be further evaluated as wound dressings or as supplementary pads for topical treatment of delayed wound healing in preclinical studies.

Orthopaedic limb salvage with a mega prosthesis in a patient with haemophilia A and inhibitors – a case report

Summary.  Inhibitors against FVIII or FIX in patients with haemophilia are a common and serious complication. Until recently, elective surgery was associated with major bleeding despite the availability of a sufficient substitution therapy. We report about the major orthopaedic reconstruction of the right limb in a patient with severe haemophilia A and inhibitors. This reconstruction was the after effect of a traumatic periprosthetic fracture of the right femur after total knee replacement 6 months ago. This fracture could be stabilized by internal fixation. Two months later, a non‐traumatic femur fracture occurred. Therefore, we removed the distal part of the femur and the joint replacement, and implanted a custom made tumour prosthesis (Type MUTARS ©, Münster). These three successive operations, which included emergency and elective surgery, were performed within 8 months. This is, to the best of our knowledge, the first patient with inhibitors undergoing such a complicated reconstruction of a limb. We conclude that successful elective orthopaedic surgery could be accomplished safely in this patient with high responding inhibitors using recombinant FVIIa. After a follow‐up of 9 months, no major complications were seen.

Simulated Osteopenia Impairs Metaphyseal Bone Ingrowth of Metal Implants in an Animal Model

Background and Purpose:Cementless total joint replacement in osteopenic bone is suspected to deteriorate long-term survival of implants because results in dental implantology research indicate that bone ingrowth of dental implants in osteoporotic bone is impaired. The present investigation was designed to determine whether osteopenic bone stock, experimentally created in ovariectomized rats, influences the active bone-implant integration process.Material and Methods:40 Sprague-Dawley rats were randomly assigned to two treatment groups; one group underwent ovariectomy, the other sham ovariectomy. Successful development of osteopenia was assessed by bone mineral density measurement of the lumbar vertebra L5 before implant surgery and before sacrifice. An uncoated and a hydroxyapatite-coated titanium implant were surgically inserted into the medullary canal of each femur. After 28 days specimens were prepared for histomorphometry to determine the osseointegrated implant surface.Results:The results showed a successful development of experimentally induced osteopenia in ovariectomized rats. For hydroxyapatite-coated implants the histomorphometry revealed a mean osseointegrated implant surface of 54.5% in the sham group versus 23.7% in the ovariectomy group. There was no significant difference for uncoated titanium implants.Conclusion:The present study in rats clearly demonstrates that osteopenic bone loss induced by ovariectomy impairs bone-implant ingrowth of hydroxyapatite-coated implants in the metaphysis of the femur. This is a potential risk for deterioration of long-term outcome of cementless metal implants in osteopenic bone. In consequence, the quality of bone stock has to be taken into account while making a decision for cemented or cementless joint replacements.

RANK-Ligand-Hemmung in der Therapie der Osteoporose

Die klinisch relevanten, haufigsten Osteoporoseformen entstehen aufgrund einer exzessiv gesteigerten osteoklastaren Knochenresorption. Hierfur kann es verschiedene Ursachen geben. Mogliche Storungen konnen in der Entstehung (Osteoklastendifferenzierung aus den Vorlauferzellen) und in der Aktivitat (Fusionsstorung, Hemmung der Apoptoseinduktion) der Osteoklasten auftreten. Das RANK/RANKL/OPG-System ist in seiner Intaktheit fur ein ausgeglichenes „bone remodeling“ verantwortlich und damit der Garant einer stabilen Knochenstruktur.

The successful development of bisphosphonates in the therapy of osteoporosis

ZusammenfassungBisphosphonate sind eine Gruppe osteotroper Substanzen, die in den letzten 30 Jahren erfolgreich bei verschiedenen Knochenerkrankungen eingesetzt werden. Seit über einer Dekade sind Bisphosphonate in oraler Form als etablierte Therapieoption der Osteoporose verfügbar und zugelassen. Die Entwicklung neuer, potenter oraler und parenteraler Bisphosphonate ermöglichte den breiten Einsatz dieser Substanzen in der Onkologie, Hämatologie und Osteologie. Sowohl im Hinblick auf die hochwirksame Therapie der Osteoporose als auch in adjuvanten Therapieansätzen oder zur Schmerztherapie sind die Bisphosphonate innovativ und stellen einen Durchbruch vor allem in der Behandlung der Osteoporose und metabolischer Osteopathien dar.AbstractIn the last 30 years bisphosphonates have been used in the treatment of different bone diseases. Bisphosphonates in their oral pharmaceutical form are an established and approved medication in osteoporosis treatment for years. Latest research developed more potent bisphosphonates in different application forms: oral and parenteral. Therefore, their prospects for medical treatment could be enlarged to the fields of oncology, hematology, and osteology. Bisphosphonates are innovative in case of adjuvant therapy as well as in adequate pain therapy. In the medical treatment of osteoporosis and metabolic osteopathies bisphosphonates could be rightly denoted as groundbreaking.

Die Entwicklung der Bisphosphonate—ein Meilenstein in der Osteoporosetherapie

ZusammenfassungBisphosphonate sind eine Gruppe osteotroper Substanzen, die in den letzten 30 Jahren erfolgreich bei verschiedenen Knochenerkrankungen eingesetzt werden. Seit über einer Dekade sind Bisphosphonate in oraler Form als etablierte Therapieoption der Osteoporose verfügbar und zugelassen. Die Entwicklung neuer, potenter oraler und parenteraler Bisphosphonate ermöglichte den breiten Einsatz dieser Substanzen in der Onkologie, Hämatologie und Osteologie. Sowohl im Hinblick auf die hochwirksame Therapie der Osteoporose als auch in adjuvanten Therapieansätzen oder zur Schmerztherapie sind die Bisphosphonate innovativ und stellen einen Durchbruch vor allem in der Behandlung der Osteoporose und metabolischer Osteopathien dar.AbstractIn the last 30 years bisphosphonates have been used in the treatment of different bone diseases. Bisphosphonates in their oral pharmaceutical form are an established and approved medication in osteoporosis treatment for years. Latest research developed more potent bisphosphonates in different application forms: oral and parenteral. Therefore, their prospects for medical treatment could be enlarged to the fields of oncology, hematology, and osteology. Bisphosphonates are innovative in case of adjuvant therapy as well as in adequate pain therapy. In the medical treatment of osteoporosis and metabolic osteopathies bisphosphonates could be rightly denoted as groundbreaking.