Surgery Combined with Local Implantation of Doxorubicin-Functionalized Hydroxyapatite Halts Tumor Growth and Prevents Bone Destruction in an Aggressive Osteosarcoma.

Osteosarcoma treatment comprises pre-surgical chemotherapy followed by radical surgery and further chemotherapy cycles, but the prognosis has been far from satisfactory. No new drugs or treatment modalities have been developed for clinical use in the last four decades. We describe a nano-hydroxyapatite (HA)-based local drug delivery platform for the delivery of doxorubicin (DOX), a cornerstone drug in osteosarcoma treatment.

Patients Aged 80 or More With Distal Radius Fractures Have a Lower One-Year Mortality Rate Than Age- and Gender-Matched Controls: A Register-Based Study.

Introduction: With a rapidly ageing population, the number of distal radius fractures (DRFs) in the elderly will increase dramatically. The aim of this retrospective register study was to examine the 1- and 5-year mortality in DRF patients aged 80 years or more and correlate the overall survival to factors not related to the fracture itself.

Material And Methods: Patients aged ≥80 diagnosed with DRFs in Lund University Hospital in Sweden in the period 2010-2012 were extracted from the prospective Lund Distal Radius Fracture register.

Systemically administered zoledronic acid activates locally implanted synthetic hydroxyapatite particles enhancing peri-implant bone formation: A regenerative medicine approach to improve fracture fixation.

Fracture fixation in an ageing population is challenging and fixation failure increases mortality and societal costs. We report a novel fracture fixation treatment by applying a hydroxyapatite (HA) based biomaterial at the bone-implant interface and biologically activating the biomaterial by systemic administration of a bisphosphonate (zoledronic acid, ZA). We first used an animal model of implant integration and applied a calcium sulphate (CaS)/HA biomaterial around a metallic screw in the tibia of osteoporotic rats.

Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA).

Virtual Follow up After Distal Radius Fracture Surgery-Patient Experiences During the COVID-19 Pandemic.

The majority of patients with a distal radius fracture (DRF) are elderly, a group known to experience difficulties with new technology, partly due to a low level of digital literacy. At the beginning of the coronavirus disease 2019 pandemic, during the spring 2020, patients that underwent DRF surgery had regular follow-ups replaced by video calls from their surgeon and physiotherapist. Afterward, patients answered questionnaires regarding health and digital literacy and took part in semistructured interviews regarding the experience of the virtual follow-up.

Association Between Radiographic and Clinical Outcomes Following Distal Radial Fractures: A Prospective Cohort Study with 1-Year Follow-up in 366 Patients.

Background: Several studies of distal radial fractures have investigated final displacement and its association with clinical outcomes. There is still no consensus on the importance of radiographic outcomes, and published studies have not used the same criteria for acceptable alignment. Previous reports have involved the use of linear or dichotomized analyses.

Systemic rifampicin shows accretion to locally implanted hydroxyapatite particles in a rat abdominal muscle pouch model.

: biomaterials combined with antibiotics are routinely used for the management of bone infections. After eluting high concentrations of antibiotics during the first week, sub-inhibitory concentrations of antibiotics may lead to late repopulation of recalcitrant bacteria. Recent studies have shown that systemically given antibiotics like tetracycline and rifampicin (RIF) could seek and bind to locally implanted hydroxyapatite (HA).

Longitudinal biodistribution of nano and micro sized hydroxyapatite particles implanted in a bone defect.

Hydroxyapatite (HA) has been widely used as a bone substitute and more recently as a carrier for local delivery of bone targeted drugs. Majority of the approved HA based biomaterials and drug carriers comprise of micrometer sized particulate HA (mHA) or granules and can therefore only be used for extracellular drug release. This shortcoming could be overcome with the use of cell penetrating HA nanoparticles (nHA) but a major concern with the clinical use of nHA is the lack of data on its biodistribution after implantation.

Evaluation of an Injectable Biphasic Calcium Sulfate/Hydroxyapatite Cement for the Augmentation of Fenestrated Pedicle Screws in Osteoporotic Vertebrae: A Biomechanical Cadaver Study.

Cement augmentation of pedicle screws is one of the most promising approaches to enhance the anchoring of screws in the osteoporotic spine. To date, there is no ideal cement for pedicle screw augmentation. The purpose of this study was to investigate whether an injectable, bioactive, and degradable calcium sulfate/hydroxyapatite (CaS/HA) cement could increase the maximum pull-out force of pedicle screws in osteoporotic vertebrae.

Extended local release and improved bacterial eradication by adding rifampicin to a biphasic ceramic carrier containing gentamicin or vancomycin.

Aims: There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Bone Remodeling after Ulna Head Replacement in Distal Radioulnar Joint Arthroplasty: A Radiographic Comparison between a Partial and a Total Ulna Head Concept.

 Ulna head arthroplasty has become an eligible solution for injury or disease in the distal radioulnar joint. Bone resorption beneath the prosthetic head is often reported, but mechanism poorly understood.  The aims were to evaluate bone remodeling and radiological instability in two conceptually different distal radioulnar joint arthroplasties: the total and the partial ulna head replacement.

Comparative effectiveness research on proximal femoral nail versus dynamic hip screw in patients with trochanteric fractures: a systematic review and meta-analysis of randomized trials.

Background: The treatments for trochanteric fractures try to regain early mobility and limit morbidity and risk of reoperations. The most currently used dynamic hip screw (DHS) and the proximal femoral nail (PFN) are both with pros and cons. We aimed to assess the comparative effectiveness of these interventions for trochanteric fractures by evaluating the surgical performance and postoperative outcomes.

A New Augmentation Method for Improved Screw Fixation in Fragile Bone.

Pertrochanteric fractures (TF) due to osteoporosis constitute nearly half of all proximal femur fractures. TFs are treated with a surgical approach and fracture fixation is achieved using metallic fixation devices. Poor quality cancellous bone in osteoporotic patients makes anchorage of a fixation device challenging, which can lead to failure of the fracture fixation.

Bone mineral: A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin.

Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA.

Forecasting effects of "fast-tracks" for surgery in the Swedish national guidelines for distal radius fractures.

Background And Purpose: National guidelines for treatment of distal radius fractures (DRFs) were presented in Sweden in 2021. In the guidelines, a fast-track is recommended for 4 subgroups of highly unstable DRFs. Regardless of the results of the closed reduction these are recommended for surgery within 1 week of injury.

A combined fracture and mortality risk index useful for treatment stratification in hip fragility fractures.

Objectives: In this study, we aimed to assess the stratification ability of the Fracture and Mortality Risk Evaluation (FAME) index for reoperation, new fragility fracture, and mortality during one-year follow-up.

Patients And Methods: Between November 2018 and July 2019, a total of 94 consecutive hip fragility fracture patients from two centers (20 males, 74 females; mean age: 79.3±8.

Different microbial and resistance patterns in primary total knee arthroplasty infections - a report on 283 patients from Lithuania and Sweden.

Background: The microbiology and the susceptibility patterns of infected total knee arthroplasties (TKAs) vary depending on demographic, local antimicrobial stewardship, and surgical factors. We wanted to compare the recent microbial profile and antimicrobial resistance pattern in revisions due to infections after primary TKAs in Sweden and Lithuania. Our hypothesis was that there is a difference in bacteriology and resistance pattern based on patient related, societal and local hospital factors as almost similar praxis have been applied for TKA surgery, short term systemic prophylaxis and routine use of local gentamicin containing bone cement.

Manufacturing of Human Tissues as off-the-Shelf Grafts Programmed to Induce Regeneration.

Design criteria for tissue-engineered materials in regenerative medicine include robust biological effectiveness, off-the-shelf availability, and scalable manufacturing under standardized conditions. For bone repair, existing strategies rely on primary autologous cells, associated with unpredictable performance, limited availability and complex logistic. Here, a conceptual shift based on the manufacturing of devitalized human hypertrophic cartilage (HyC), as cell-free material inducing bone formation by recapitulating the developmental process of endochondral ossification, is reported.

Sustained and controlled delivery of doxorubicin from an in-situ setting biphasic hydroxyapatite carrier for local treatment of a highly proliferative human osteosarcoma.

Doxorubicin (DOX) is a cornerstone drug in the treatment of osteosarcoma. However, achieving sufficient concentration in the tumor tissue after systemic administration with few side effects has been a challenge. Even with the most advanced nanotechnology approaches, less than 5% of the total administered drug gets delivered to the target site.

Augmenting a dynamic hip screw with a calcium sulfate/hydroxyapatite biomaterial.

Internal fixation failure in hip fractures can lead to reoperation. Calcium sulfate/hydroxyapatite (CaS/HA) is a biomaterial that can be used for augmenting fracture fixation. We aimed to determine whether an injection of 2 ml CaS/HA increases the fixation of a dynamic hip screw inserted in synthetic and human trabecular bone.

Dual modality neutron and x-ray tomography for enhanced image analysis of the bone-metal interface.

The bone tissue formed at the contact interface with metallic implants, particularly its 3D microstructure, plays a pivotal role for the structural integrity of implant fixation. X-ray tomography is the classical imaging technique used for accessing microstructural information from bone tissue. However, neutron tomography has shown promise for visualising the immediate bone-metal implant interface, something which is highly challenging with x-rays due to large differences in attenuation between metal and biological tissue causing image artefacts.

Synthesis and Characterization of a Biocomposite Bone Bandage for Controlled Delivery of Bone-Active Drugs in Fracture Nonunions.

Fracture nonunions are common in orthopedics and their treatment often involves multiple surgical interventions. The aim of this study was to fabricate and characterize a gelatin-nano-hydroxyapatite membrane (GM)-based bone bandage for controlled delivery of bio-active molecules; recombinant human bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) to promote osteoinduction and prevent callus resorption, respectively. In vitro cell-material interaction experiments using MC3T3 cells seeded on the GM indicated good biocompatibility.

Bone mineral as a drug-seeking moiety and a waste dump.

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual's lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules.

A facile one-stage treatment of critical bone defects using a calcium sulfate/hydroxyapatite biomaterial providing spatiotemporal delivery of bone morphogenic protein-2 and zoledronic acid.

Bone morphogenic proteins (BMPs) are the only true osteoinductive molecules. Despite being tremendously potent, their clinical use has been limited for reasons including supraphysiological doses, suboptimal delivery systems, and the pro-osteoclast effect of BMPs. Efforts to achieve spatially controlled bone formation using BMPs are being made.

Bone Damage Evolution Around Integrated Metal Screws Using X-Ray Tomography - Pullout and Digital Volume Correlation.

Better understanding of the local deformation of the bone network around metallic implants subjected to loading is of importance to assess the mechanical resistance of the bone-implant interface and limit implant failure. In this study, four titanium screws were osseointegrated into rat tibiae for 4 weeks and screw pullout was conducted under x-ray microtomography, recording macroscopic mechanical behavior and full tomographies at multiple load steps before failure. Images were analyzed using Digital Volume Correlation (DVC) to access internal displacement and deformation fields during loading.