Search

Bone has a remarkable capability to self-repair. However, in some cases the patient may be left with bone defects beyond a critical size which cannot be healed through natural processes alone. In these cases, patients often require reconstructive surgery to support healing. There are multiple limitations affecting current treatment options. Therefore, there is a major clinical need for well performing bone graft substitutes which has led to the development of the field of bone tissue engineering. Bone tissue engineering aims to regenerate viable bone by the use of biomaterials, cellular therapies and/or growth factors. The development of biomaterials for bone tissue engineering is especially important because biomaterials not only facilitate the production of bone but simultaneously provide structural support for tissue regeneration. Bone presents manifold requirements for creating optimal bone grafts. No material alone has been able to fully replicate the properties of bone. Therefore, a composite containing a polymeric matrix and a bioceramic phase provides a promising option for bone tissue engineering applications. Bioactive glasses (BAG) are a group of bioceramics with the ability to stimulate more bone regeneration than any other bioceramic. Also, biomaterial scaffolds releasing bone-growth inducing active agents have been suggested to enhance osteogenic differentiation in vitro and in vivo. Though bone-growth inducing active agents are extensively used in cell cultivation, they have not been widely incorporated into scaffolds. L-ascorbic acid 2-phosphate trisodium salt (AS) is a bone-growth inducing active agent which has been shown to stimulate proliferation and osteogenic differentiation of human osteoblasts and human bone marrow stem cells. In this study, bioabsorbable composites of poly(L-lactide-co-ε-caprolactone) (PLCL), β-tricalcium phosphate (β-TCP) and one of two BAGs; 45S5 or a borosilicate BAG, were synthesized and incorporated with AS. The study focused on assessing the potential of the developed composites for bone applications in vitro. The aim was to study how AS impacts the in vitro dissolution properties of the composites and whether the release of BAG ions and AS from the composites can be controlled to, potentially, enhance osteoinduction. The study was divided into four sub-studies: I) AS stability studies, II) AS release from composites, III) assessment of the impact of AS on the release of BAG ions and degradation of the composite, and IV) bioactivity investigation. This study revealed that AS enhances the release of BAG ions from BAG/β-TCP/PLCL composites. Furthermore, the presence of a bioceramic phase in the composites accelerated the re-lease of AS. The study demonstrated that AS restricts or profoundly delays the formation of hydroxyapatite on the surface of BAG/β-TCP/PLCL composites in vitro. The addition of AS to the composite did not change the surface hydrophilicity of the material, but the overall hydrophilicity of the material significantly increased. The study introduced novel composites that have potential for applications in bone tissue engineering.

Background Due to unmet need for bone augmentation, our aim was to promote osteogenic differentiation of human adipose stem cells (hASCs) encapsulated in gellan gum (GG) or collagen type I (COL) hydrogels with bioactive glass (experimental glass 2-06 of composition [wt-%]: Na2O 12.1, K2O 14.0, CaO 19.8, P2O5 2.5, B2O3 1.6, SiO2 50.0) extract based osteogenic medium (BaG OM) for bone construct development. GG hydrogels were crosslinked with spermidine (GG-SPD) or BaG extract (GG-BaG). Methods Mechanical properties of cell-free GG-SPD, GG-BaG, and COL hydrogels were tested in osteogenic medium (OM) or BaG OM at 0, 14, and 21 d. Hydrogel embedded hASCs were cultured in OM or BaG OM for 3, 14, and 21 d, and analyzed for viability, cell number, osteogenic gene expression, osteocalcin production, and mineralization. Hydroxyapatite-stained GG-SPD samples were imaged with Optical Projection Tomography (OPT) and Selective Plane Illumination Microscopy (SPIM) in OM and BaG OM at 21 d. Furthermore, Raman spectroscopy was used to study the calcium phosphate (CaP) content of hASC-secreted ECM in GG-SPD, GG-BaG, and COL at 21 d in BaG OM. Results The results showed viable rounded cells in GG whereas hASCs were elongated in COL. Importantly, BaG OM induced significantly higher cell number and higher osteogenic gene expression in COL. In both hydrogels, BaG OM induced strong mineralization confirmed as CaP by Raman spectroscopy and significantly improved mechanical properties. GG-BaG hydrogels rescued hASC mineralization in OM. OPT and SPIM showed homogeneous 3D cell distribution with strong mineralization in BaG OM. Also, strong osteocalcin production was visible in COL. Conclusions Overall, we showed efficacious osteogenesis of hASCs in 3D hydrogels with BaG OM with potential for bone-like grafts.

The development of safe and practical strategies to prevent weakening of bone tissue is vital, yet attempts to achieve this have been hindered by a lack of understanding of the short‐term (days‐weeks) physiology of bone collagen turnover. To address this, we have developed a method to quantify bone collagen synthesis in vivo, using deuterium oxide (D2O) tracer incorporation techniques combined with gas chromatography pyrolysis isotope‐ratio mass spectrometry (GC‐pyrolysis‐IRMS). Forty‐six male and female rats from a selectively bred model ingested D2O for 3 weeks. Femur diaphyses (FEM), tibia proximal (T‐PRO), and distal (T‐DIS) epiphyses‐metaphyses and tibia mid‐shaft diaphyses (T‐MID) were obtained from all rats after necropsy. After demineralisation, collagen proteins were isolated and hydrolysed and collagen fractional synthetic rates (FSRs) determined by incorporation of deuterium into protein‐bound alanine via GC‐pyrolysis‐IRMS. The collagen FSR for the FEM (0.131 ± 0.078%/day; 95% CI [0.106–0.156]) was greater than the FSR at T‐MID (0.055 ± 0.049%/day; 95% CI [0.040–0.070]; p, We have developed a method to quantify bone collagen synthesis in vivo, using D2O in adult rodents combined with highly sensitive GC‐pyrolysis‐IRMS techniques. This method is ideally suited to the measurement of slow turnover proteins, such as collagen, and its high sensitivity will permit the application of D2O loading protocols that are well tolerated in humans (i.e., 150 ml + 50 ml/week‐1). Therefore, our D2O GC‐pyrolysis‐IRMS approach has great potential applicability to study human bone collagen turnover.

Understanding how bones are innately designed, robustly developed and delicately maintained through intricate anatomical features and physiological processes across the lifespan is vital to inform our assessment of normal bone health, and essential to aid our interpretation of adverse clinical outcomes affecting bone through primary or secondary causes. Accordingly this review serves to introduce new researchers and clinicians engaging with bone and mineral metabolism, and provide a contemporary update for established researchers or clinicians. Specifically, we describe the mechanical and non-mechanical functions of the skeleton; its multidimensional and hierarchical anatomy (macroscopic, microscopic, organic, inorganic, woven and lamellar features); its cellular and hormonal physiology (deterministic and homeostatic processes that govern and regulate bone); and processes of mechanotransduction, modelling, remodelling and degradation that underpin bone adaptation or maladaptation. In addition, we also explore commonly used methods for measuring bone metabolic activity or material features (imaging or biochemical markers) together with their limitations. peerReviewed

Androgen deprivation therapy (ADT) improves survival in men with advanced prostate cancer (PCa), but has been associated with compromised skeletal health and increased fracture risk. However, limited previous research has investigated determinants of bone strength beyond DXA-derived areal bone mineral density (aBMD) in this population group. The aim of this cross-sectional study was to investigate the effects of ADT in men with PCa on BMD, bone structure, estimates of whole bone strength and cortical bone distribution. A total of 70 ADT-treated men, 52 PCa controls and 70 healthy controls had DXA lumbar spine and proximal femur aBMD and pQCT distal (4%) and proximal (66%) tibia and radius cortical and trabecular volumetric BMD (vBMD), bone structure, strength and cortical bone distribution assessed. Analyses included BMI and/or tibia/radius length as covariates. On average, ADT-treated men had a higher BMI than PCa (P

TIIVISTELMÄ Kovatehoisen, iskutyyppisen harjoittelun vaikutukset reisiluun kaulan lujuuteen lievää polven nivelrikkoa sairastavilla postmenopausaali-ikäisillä naisilla. Satunnaistettu kontrolloitu tutkimus. Janhunen, Eija Fysioterapian Pro Gradu- tutkielma Jyväskylän yliopisto, Liikuntatieteellinen tiedekunta, Terveystieteiden laitos 2013 Sivuja 79 Ohjaajat: Prof. Ari Heinonen ja THM Juhani Multanen, Jyväskylän Yliopisto, Terveystieteiden laitos Tämän satunnaistetun kontrolloidun tutkimuksen tarkoituksena oli tutkia 12 kuukautta kestäneen iskutyyppisen harjoittelun vaikutuksia reisiluun kaulan lujuuteen lievää polven nivelrikkoa sairastavilla postmenopausaali-ikäisillä naisilla. Kahdeksankymmentä (80) naista, ikä keskimäärin 57.7 vuotta (SD 4.1), polven osteoartroosi (OA) luokitus Kellgren-Lawrence (K/L) 1-2 satunnaistettiin valvottuun, kovatehoiseen harjoitteluryhmään (40 harjoitteluryhmään ja 40 kontrolliryhmään). Reisiluun kaula skannattiin DXA- laitteella alkutilanteessa ja 12 kuukauden intervention jälkeen 36 harjoitteluun osallistuneelta ja 40 kontrollihenkilöltä. Luun taivutusvastus (Z), luun poikkipinta-ala (CSA) ja luukalvon alainen reisiluun kaulan luun leveys (W) analysoitiin sekä affektoituneelta että ei-affektoituneelta puolelta. Dynaaminen tasapaino mitattiin kahdeksikkojuoksutestillä, staattinen tasapaino tasapainolevyllä, maksimaalinen isometrinen polvenojennusvoima dynamometrillä sekä verenkiertoelimistön kunto (VO2max) arvioitiin vakioidulla 2 km:n kävelytestillä. Itsearvioitu polvikipu, jäykkyys ja fyysinen toimintakyky määritettiin Western Ontario and McMaster Universities Arthritis Index:illä (WOMAC). Intervention vaikutusta arvioitiin vertaamalla lopputilanteessa ryhmiä toisiinsa ANCOVA:n avulla, lähtötilanne kovariaattina. Alkutilanteella adjustoduissa arvoissa affektoituneella puolella ryhmien välillä oli tilastollisesti merkitsevä 4.2 % ero Z:ssa harjoitteluryhmän eduksi (p=0.018), CSA 1.1 % (p=0.074) ja W 1.2 % (p=0.471) eivät eronneet merkitsevästi ryhmien välillä. Toissijaisten muuttujien osalta harjoitteluryhmä paransi 2,9 % (p=0.002) dynaamista tasapainoa, arvioitua sydän- ja verenkiertoelimistön kuntoa (VO2max) 5.1 % (p=0.023) enemmän kuin kontrolliryhmä. Staattisessa tasapainossa, polvenojennusvoimassa ja WOMAC pisteissä (polvikipu, jäykkyys ja toimintakyky) ei havaittu eroja. Tämän tutkimuksen tulokset osoittavat, että kovatehoinen harjoittelu voi lisätä reisiluun kaulan vahvuutta parantamalla luun rakenteellisia ominaisuuksia nivelrikosta kärsivillä, postmenopausaalisilla naisilla. Harjoittelu ei kuitenkaan lisännyt polven OA:n oireita. Asiasanat: luun rakenne, reisiluun kaula, iskutyyppinen harjoittelu, luun vahvistaminen, osteoporoosi ABSTRACT Effects of high-impact training on femoral neck structure in postmenopausal-aged women with mild knee osteoarthritis: a 12-month randomized controlled exercise intervention. Randomized controlled study. Eija Janhunen Physiotherapy Master’s Thesis University of Jyväskylä, Faculty of Sports Sciences Department of Health Sciences 2013 79 pages Supervisors: Professor Ari Heinonen, M.Sc. Juhani Multanen, University of Jyväskylä, Department of Health Sciences This study investigated the training effects of a 12-month exercise intervention on femoral neck bone strength in postmenopausal-aged women with mild knee osteoarthritis (OA). 80 women,mean age 58 (SD 4.1) with Kellgren-Lawrence (K/L) grading of knee OA 1 and 2, were randomly assigned into a supervised progressive high-impact exercise (40 trainees and 40 controls). At baseline and 12 months, dual-emission X-ray absorptiometry (DXA) data on 36 trainees and 40 control participants were available for hip structural analysis. The section modulus (Z), cross-sectional area (CSA), and subperiosteal width (W) at the femoral neck were analyzed from both affected and no-affected knee side. Dynamic balance was measured with figure-of-eight running test, static balance with balance board, maximal isometric knee extension force and cardiorespiratory fitness (VO2-max) were assessed by dynamometer and standardized 2-km walking test. Subscores for self-perceived knee pain, stiffness, and self-rated physical functioning were assessed with the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Effects of the intervention were assessed at the end by comparing groups with ANCOVA using baseline as covariate. The baseline adjusted between-group differences on the affected side were observed after the 12-month intervention in favour of trainees in Z 4.2% (p = 0.018). There were no significant difference in CSA 1.1%, (p = 0.074) and in Width 1.2 (p=0.471) between the groups. In the secondary outcomes the exercise group improved 2.9 % (p=0.002) more dynamic balance,, 5.1 % estimated VO2-max (p=0.023) more than the control group. There were no differences between-groups in static balance, isometric knee extension force and WOMAC subscores (pain, stiffness and functional ability). The results of this study indicated that high-impact exercise can increase the femoral neck strength by improving the structural properties of bone in postmenopausal women. However, symptoms did not increase in OA knee. Keywords: bone structure, femoral neck, high-impact exercise, bone strengthening, osteoporosis