In vivo biofunctional evaluation of hydrogels for disc regeneration

Purpose

Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model.

Methods

In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted.

Results

Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration.

Conclusions

None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning.     

Effect of disc degeneration on the mechanical behavior of the human lumbar spine: a probabilistic finite element study

BACKGROUND CONTEXT

Intervertebral disc degeneration has been subject to numerous in vivo and in vitro investigations and numerical studies during recent decades, reporting partially contradictory findings. However, most of the previous studies were limited in the number of specimens investigated and, therefore, could not consider the vast variety of the specimen geometries, which are likely to strongly influence the mechanical behavior of the spine.

Effect of zinc supplementation on growth in West African children: a randomized double-blind placebo-controlled trial in rural Burkina Faso

OBJECTIVE: To analyse the effects of zinc supplementation on growth parameters in a representative sample of young children in rural Burkina Faso. Design Randomized, double-blind, placebo-controlled efficacy trial. Setting Eighteen villages in rural northwestern Burkina Faso. Subjects In all, 709 children aged 6-31 months were enrolled; 685 completed the trial. Intervention Supplementation with zinc (12.5 mg zinc sulphate) or placebo daily for 6 days a week for 6 months. Outcomes Weight, length/height, mid-arm circumference, and serum zinc. RESULTS: In a representative subsample of study children, 72% were zinc-deficient at baseline. After supplementation, serum zinc increased in zinc-supplemented but not in control children of the subsample. No significant differences between groups were observed during follow-up regarding length/height, weight, mid-arm circumference, and z scores for height-for-age, weight-for-age, and weight-for-height. CONCLUSIONS: We conclude that zinc supplementation does not have an effect of public health importance on growth in West African populations of young children with a high prevalence of malnutrition. Multinutrient interventions are likely to be more effective.     

Strontium(II) and mechanical loading additively augment bone formation in calcium phosphate scaffolds

Calcium phosphate cements (CPCs) are widely used for bone‐defect treatment. Current developments comprise the fabrication of porous scaffolds by three‐dimensional plotting and doting using biologically active substances, such as strontium. Strontium is known to increase osteoblast activity and simultaneously to decrease osteoclast resorption. This study investigated the short‐ and long‐term in vivo performances of strontium(II)‐doted CPC (SrCPC) scaffolds compared to non‐doted CPC scaffolds after implantation in unloaded or load‐bearing trabecular bone defects in sheep. After 6 weeks, both CPC and SrCPC scaffolds exhibited good biocompatibility and osseointegration. Fluorochrome labeling revealed that both scaffolds were penetrated by newly formed bone already after 4 weeks. Neither strontium doting nor mechanical loading significantly influenced early bone formation. In contrast, after 6 months, bone formation was significantly enhanced in SrCPC compared to CPC scaffolds. Energy dispersive X‐ray analysis demonstrated the release of strontium from the SrCPC into the bone. Strontium addition did not significantly influence material resorption or osteoclast formation. Mechanical loading significantly stimulated bone formation in both CPC and SrCPC scaffolds after 6 months without impairing scaffold integrity. The most bone was found in SrCPC scaffolds under load‐bearing conditions. Concluding, these results demonstrate that strontium doting and mechanical loading additively stimulated bone formation in CPC scaffolds and that the scaffolds exhibited mechanical stability under moderate load, implying good clinical suitability. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:106–117, 2018.     

What does the shape of our back tell us? Correlation between sacrum orientation and lumbar lordosis

Background Context

Sacral slope and lumbar lordosis (LL) have been studied extensively in recent years via X-ray examinations and strongly correlate with each other. This raises, first, the question of the reproducibility of this correlation in multiple standing phases and, second, if this correlation can be achieved using non-radiological measurement tools.

Health-seeking patterns among fatally ill Capeverdian women

The circumstances of 94 deaths among females aged 15-49 years in Cape Verde were investigated to assess their access to effective care. Persons associated with the deceased women were interviewed (verbal autopsy) to explore contributing causes of death, perceived illnesses and treatment efforts. The certainty of diagnosis and avoidability of the fatal outcome were assessed by a panel ofexperts. A model of health care accessibility is elaborated to identity restricting (delay) factors. Deliberate avoidance of modern medical care and reliance on traditional medicine were major delay factors, while unawareness of the severity of symptoms and affordability limits were minor delay factors in this population. A detailed sorting of cases by health care level is used to identify the effectiveness of diagnosing, referral and care provided. Since a high proportion of avoidable deaths occurred in hospital, the quality of care may have been sub-optimal.     

Deaths among women of reproductive age in Cape Verde: causes and avoidability

SUBJECT: In 1992-93 all deaths (n=97) of women 15 to 49 years old in three islands of Cape Verde were investigated to determine the cause of death, the maternal mortality ratio, the reliability of cause-of-death ascertainment, and the level of avoidability. METHOD: Data were obtained through interviews with the deceased person's family members and other knowledgeable persons (verbal autopsy) and through hospital files. RESULTS: The overall mortality rate was 163 per 100,000 women 1549 years old, and the maternal mortality ratio was 127 per 100,000 live births. A plausible diagnosis could be determined in 77%. The most frequent causes of death were circulatory disorders, external causes, maternal causes, infectious diseases. and neoplasms. CONCLUSIONS: It was estimated that three of four of the deaths were avoidable with locally available resources. Since access to health care in the study area is not a major hindrance, a further decrease of female mortality depends mainly on improved quality of care in health facilities.     

CARP, a cardiac ankyrin repeat protein, is up-regulated during wound healing and induces angiogenesis in experimental granulation tissue

Cardiac ankyrin repeat protein (CARP) was identified by subtractive hybridization as one of a group of genes that are rapidly modulated by acute wounding of mouse skin. Quantitative RT-PCR showed that CARP was strongly induced during the first day after wounding (157.1-fold), and the high level persisted for up to 14 days. Immunohistochemistry and in situ hybridization revealed that CARP was expressed in skeletal muscle, vessel wall, hair follicle, inflammatory cells, and epidermis in the wound area. To examine the effects of CARP on wound healing, we developed an adenoviral CARP vector to treat subcutaneously implanted sponges in either rats or Flk-1(LacZ) knock-in mice. Four days after infection, CARP-infected sponges in rats showed a remarkable increase in the vascular component in granulation tissue as compared to Ad-LacZ controls. This result was confirmed by CD34 immunostaining. By 7 days post-infection of sponge implants in Flk-1(LacZ) knock-in mice, granulation tissue showed many more LacZ-positive cells in Ad-CARP-infected sponges than in virus controls. Ad-CARP treatment also induced neovascularization and increased blood perfusion in rabbit excisional wounds in and ischemic rat wounds. These findings indicate that CARP could play a unique role in therapeutic angiogenesis during wound healing.     

Learning about the experience of living with chronic conditions: A framework analysis of nursing students’ reflections on their conversations with older adults

Preparing nursing students to work effectively with older adults is an important element of undergraduate nursing education. Reflective journals written as course assignments represent a source of data about students’ learning. The aim of this study was to analyze nursing students’ reflective journals based on conversations with older adults who are community dwelling, to identify learning in relation to experiences of living with a chronic condition. This was one element of a wider study to evaluate learning partnerships between older adults who are community dwelling and nursing students as an alternative to traditional clinical placements in long-term care settings. Nursing students worked with faculty to complete a qualitative secondary analysis of 47 journals utilizing framework analysis. Students learned about three main aspects of living with chronic conditions: beliefs about chronic conditions, managing chronic conditions, and experiencing chronic conditions, with some evidence that these themes may be interconnected. Findings suggest that learning partnerships with older adults combined with reflective journaling enable nursing students to understand the experience of chronic conditions in later life as reflected within current literature and to identify interventions for gerontological nursing practice. Enabling nursing students to recognize the highly skilled nature of working with older adults with chronic illness has the potential to influence their future career choices.