A clinically relevant model of osteoinduction: a process requiring calcium phosphate and BMP/Wnt signalling

In this study, we investigated a clinically relevant model of in vivo ectopic bone formation utilizing human periosteum derived cells (HPDCs) seeded in a Collagraft carrier and explored the mechanisms by which this process is driven. Bone formation occurred after eight weeks when a minimum of one million HPDCs was loaded on Collagraft carriers and implanted subcutaneously in NMRI nu/nu mice. De novo bone matrix, mainly secreted by the HPDCs, was found juxta-proximal of the calcium phosphate (CaP) granules suggesting that CaP may have triggered the 'osteoinductive program'. Indeed, removal of the CaP granules by ethylenediaminetetraacetic acid decalcification prior to cell seeding and implantation resulted in loss of bone formation. In addition, inhibition of endogenous bone morphogenetic protein and Wnt signalling by overexpression of the secreted antagonists Noggin and Frzb, respectively, also abrogated osteoinduction. Proliferation of the engrafted HPDCs was strongly reduced in the decalcified scaffolds or when seeded with adenovirus-Noggin/Frzb transduced HPDCs indicating that cell division of the engrafted HPDCs is required for the direct bone formation cascade. These data suggest that this model of bone formation is similar to that observed during physiological intramembranous bone development and may be of importance when investigating tissue engineering strategies.Published versio

The child psychotherapists' role in consultation work with the professional network around looked after children

Consultation with the network around a child is a core aspect of a child psychotherapist’s role; however, little has been written about this aspect of their work with looked after children. Aims: To gain an understanding of child psychotherapists’ work with the network around looked after children, and what they see as specific to the psychoanalytic approach. Methods: Nine participants with expertise in working with foster carers and looked after children’s professionals, participated in in-depth interviews. Results: Thematic analysis identified three themes concerned with the tensions child psychotherapists hold within themselves whilst consulting to the network around looked after children. The first theme encapsulates participants’ sense of dilemma between what they felt was demanded of them versus what they could offer. The second theme describes participants’ sense of tensions around the way the system is organised versus what they felt is in the best interests of the child and network. The third theme captures participants’ views about whether their consultant role fits a generic model of reflective practice similar to that offered by professionals from other disciplines, or whether the psychoanalytic approach brings something distinctive to this model of consultation. Links to existing theory and practice implications are discussed

Psychodynamic therapy of depression

In this journal, Malhi et al. (2021) present the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders While we applaud their efforts to develop a comprehensive treatment guideline, we call attention to several factual errors leading to erroneous conclusions and recommendations with regard to the treatment of mood disorders

Narcissistic Personality Disorder: Are Psychodynamic Theories and the Alternative DSM-5 Model for Personality Disorders Finally Going to Meet?

Narcissistic Personality Disorder is the new borderline personality disorder of our current era. There have been recent developments on narcissism that are certainly worthwhile examining. Firstly, relational and intersubjective psychoanalysts have been rethinking the underlying concepts of narcissism, focusing on the development of self and relations to others. Secondly, in the DSM-5, the Alternative DSM-5 Model for Personality Disorders (AMPD) was presented for a dimensional evaluation of the severity of personality disorder pathology. The combined dimensional and trait conceptualization of NPD opened the door to new integrated diagnostic perspectives, including both internal and interpersonal functioning. Finally, Pincus and Lukowitsky encourage clinicians to use a hierarchical model of pathological narcissism, as it opens up opportunities for shared points of interest in empirical research from different scholarly perspectives. As for most non-psychodynamic clinicians and researchers the DSM-5 clearly bears dominant weight in their work, we will take the AMPD model for NPD as our point of reference. We will discuss the narcissist's unique pattern of self-impairments in identity and self-direction, and of interpersonal disfunctioning (evaluated by assessing empathy and intimacy). Subsequently, we will examine how contemporary psychodynamic theories and the hierarchical model of Pincus and Lukowitsky additionally inform or contradict the AMPD. For us, one of the big advantages of the AMPD is the use of structured clinical evaluations of disturbances of the self and interpersonal functioning and the dimensional evaluation of severity. As psychodynamically oriented therapists, we are enthusiastic about the opportunities for inclusion of psychodynamic concepts, but we also discuss a number of sticking points

Coupling curvature-dependent and shear stress-stimulated neotissue growth in dynamic bioreactor cultures: a 3D computational model of a complete scaffold.

The main challenge in tissue engineering consists in understanding and controlling the growth process of in vitro cultured neotissues toward obtaining functional tissues. Computational models can provide crucial information on appropriate bioreactor and scaffold design but also on the bioprocess environment and culture conditions. In this study, the development of a 3D model using the level set method to capture the growth of a microporous neotissue domain in a dynamic culture environment (perfusion bioreactor) was pursued. In our model, neotissue growth velocity was influenced by scaffold geometry as well as by flow- induced shear stresses. The neotissue was modeled as a homogenous porous medium with a given permeability, and the Brinkman equation was used to calculate the flow profile in both neotissue and void space. Neotissue growth was modeled until the scaffold void volume was filled, thus capturing already established experimental observations, in particular the differences between scaffold filling under different flow regimes. This tool is envisaged as a scaffold shape and bioprocess optimization tool with predictive capacities. It will allow controlling fluid flow during long-term culture, whereby neotissue growth alters flow patterns, in order to provide shear stress profiles and magnitudes across the whole scaffold volume influencing, in turn, the neotissue growth

Mapping human serum induced gene networks as a basis for the creation of biomimetic periosteum for bone repair

The periosteum is a highly vascularised, collagen-rich tissue that plays a crucial role in directing bone repair. This is orchestrated primarily by its resident progenitor cell population. Indeed, preservation of periosteum integrity is critical for bone healing. Cells extracted from the periosteum retain their osteochondrogenic properties and as such are a promising basis for tissue engineering strategies for the repair of bone defects. However, the culture expansion conditions, and the way in which the cells are reintroduced to the defect site are critical aspects of successful translation. Indeed, expansion in human serum and implantation on biomimetic materials has previously been shown to improve in vivo bone formation. As such, this study aimed to develop a protocol to allow for the expansion of human periosteum derived cells (hPDCs) in a biomimetic periosteal-like environment. The expansion conditions were defined through the investigation of the bioactive cues involved in augmenting hPDC proliferative and multipotency characteristics, based on transcriptomic analysis of cells cultured in human serum. Master regulators of transcriptional networks were identified and an optimised periosteal derived-growth factor cocktail (PD-GFC; containing β-Estradiol, FGF2, TNFα, TGFβ, IGF-1 and PDGF-BB) was generated. Expansion of hPDCs in PD-GFC resulted in serum mimicry with regards to the cell morphology, proliferative capacity and chondrogenic differentiation. When incorporated into a 3D collagen-type-1 matrix and cultured in PD-GFC, the hPDCs migrated to the surface that represented the matrix topography of the periosteum cambium layer. Furthermore, gene expression analysis revealed a downregulated Wnt and TGFβ signature and an upregulation of CREB, which may indicate the hPDCs are recreating their progenitor cell signature. This study highlights the first stage in the development of a biomimetic periosteum which may have applications in bone repair