The use of PRP injections in the management of knee osteoarthritis.

Osteoarthritis (OA) is a degenerative disease involving joint damage, an inadequate healing response and progressive deterioration of the joint architecture that commonly affects the knee and/or hip joints. It is a major world public health problem and is predicted to increase rapidly with an ageing population and escalating rate of obesity. Autologous blood-derived products possess much promise in the repair and regeneration of tissue and have important roles in inflammation, angiogenesis, cell migration and metabolism in pathological conditions, including OA. Utilising platelet-rich plasma (PRP) to treat tendon, ligament and skeletal muscle has shown variable results across many studies with the current evidence base for the efficacy of PRP in treating sports injuries remaining inconclusive. More uniformly positive results have been observed by various studies for PRP in OA knee in comparison to hyaluronic acid, other intra-articular injections and placebo than in other musculoskeletal tissue. However, methodological concerns as well as satisfactory PRP product classification prevent the true characterisation of this treatment. Thus, further research is required to investigate how leukocyte inclusion, activation and platelet concentration affect therapeutic efficacy. Furthermore, the optimisation of timing, dosage, volume, frequency and rehabilitation strategies need to be ascertained. For knee OA management, these concerns must be addressed before this promising treatment can be widely implemented

Rotator Cuff Repair Augmentation Using Osteoinductive Growth Factors

Rotator cuff injuries (RCIs) present a major health problem due to high incidences of degenerative tears greater than 3 cm and prevalence of re-tears following surgical procedures. Since healing and functional restoration relies upon bone ingrowth into the tendon, it is hypothesised that sustained delivery of osteoinductive factors including bone morphogenetic proteins (BMPs), specifically BMP2–7, may significantly improve RCI tendon-bone healing. Here, growth factor candidates and delivery mechanisms are reviewed, specifically for improved RCI healing through enhanced bone ingrowth. In addition to BMPs, other potentially osteogenic factors including platelet-derived growth factors (PDGF), fibroblast growth factor (FGF), transforming growth beta isoforms (TGF-β1 and TGF-3) and parathyroid hormone (PTH) are evaluated since they can induce bone formation at the healing tendon attachment site. Several challenges must be addressed prior to clinical translation. The majority of published studies utilise in vivo animal models. In general, BMP-7 demonstrates a stronger stimulating effect when compared to BMP-2; the reported effectiveness of BMP-2 is often conflicting. Alternative factors, including PDGF and PTH, also demonstrate potential for assisting bone growth in enthesis healing. The use of sustained and biomimetic delivery systems appears to have the greatest positive effects. Some studies have demonstrated a dose-dependent effect, in conjunction with varying age, indicating that stratified therapies could be a viable solution for RCI healing. To adequately resolve potential treatments for RCI, further expanded and correlated animal trials must be undertaken, and indicative human trials are required with consideration of surgical and patient-specific influences

Intraarticular injection of bone marrow-derived mesenchymal stem cells enhances regeneration in knee osteoarthritis.

PURPOSE: This review aimed to evaluate the efficacy of intra-articular injections of bone marrow derived mesenchymal stem cells (BM-MSCs) for the treatment of knee osteoarthritis (KOA). METHODS: This narrative review evaluates recent English language clinical data and published research articles between 2014 and 2019. Key word search strings of ((("bone marrow-derived mesenchymal stem cell" OR "bone marrow mesenchymal stromal cell" OR "bone marrow stromal cell")) AND ("osteoarthritis" OR "knee osteoarthritis")) AND ("human" OR "clinical"))) AND "intra-articular injection" were used to identify relevant articles using PMC, Cochrane Library, Web Of Science and Scopus databases. RESULTS: Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of BM-MSCs, which have shown to augment pain and improve functional outcomes. Subsequently, clinical applications of intra-articular injections of BM-MSCs are steadily increasing, with most studies demonstrating a decrease in poor cartilage index, improvements in pain, function and Quality of Life (QoL); with moderate-to-high level evidence regarding safety for therapeutic administration. However, low confidence in clinical efficacy remains due to a plethora of heterogenous methodologies utilised, resulting in challenging study comparisons. A moderate number of cells (40 × 106) were identified as most likely to achieve optimal responses in individuals with grade ≥ 2 KOA. Likewise, significant improvements were reported when using lower (24 × 106) and higher (100 × 106) cell numbers, although adverse effects including persistent pain and swelling were a consequence. CONCLUSION: Overall, the benefits of intra-articular injections of BM-MSCs were deemed to outweigh the adverse effects; thus, this treatment be considered as a future therapy strategy. To realise this, long-term large-scale randomised clinical trials are required to enable improved interpretations, to determine the validity of efficacy in future studies. LEVEL OF EVIDENCE: IV

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing.

There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue injuries and disorders. Currently, several therapies are emerging and undergoing trials in animal models; these focus on the manipulation and administration of several growth factors implicated with healing. However, limitations include in vivo instability, reliance on biocompatible and robust carriers and restricted application procedures (local and direct). The aim of this paper is therefore to critically review the current literature surrounding the use of BPC 157, as a feasible therapy for healing and functional restoration of soft tissue damage, with a focus on tendon, ligament and skeletal muscle healing. Currently, all studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models and the efficacy of BPC 157 is yet to be confirmed in humans. Further, over the past two decades, only a handful of research groups have performed in-depth studies regarding this peptide. Despite this, it is apparent that BPC 157 has huge potential and following further development has promise as a therapy to conservatively treat or aid recovery in hypovascular and hypocellular soft tissues such as tendon and ligaments. Moreover, skeletal muscle injury models have suggested a beneficial effect not only for disturbances that occur as a result of direct trauma but also for systemic insults including hyperkalamia and hypermagnesia. Promisingly, there are few studies reporting any adverse reactions to the administration of BPC 157, although there is still a need to understand the precise healing mechanisms for this therapy to achieve clinical realisation

A critical review of current progress in 3D kidney biomanufacturing: advances, challenges, and recommendations

The widening gap between organ availability and need is resulting in a worldwide crisis, particularly concerning kidney transplantation. Regenerative medicine options are becoming increasingly advanced and are taking advantage of progress in novel manufacturing techniques, including 3D bioprinting, to deliver potentially viable alternatives. Cell-integrated and wearable artificial kidneys aim to create convenient and efficient systems of filtration and restore elements of immunoregulatory function. Whilst preliminary clinical trials demonstrated promise, manufacturing and trial design issues and identification of suitable and sustainable cell sources have shown that more development is required for market progression. Tissue engineering and advances in biomanufacturing techniques offer potential solutions for organ shortages; however, due to the complex kidney structure, previous attempts have fallen short. With the recent development and progression of 3D bioprinting, cell positioning and resolution of material deposition in organ manufacture have never seen greater control. Cell sources for constructing kidney building blocks and populating both biologic and artificial scaffolds and matrices have been identified, but in vitro culturing and/or differentiation, in addition to maintaining phenotype and viability during and after lengthy and immature manufacturing processes, presents additional problems. For all techniques, significant process barriers, clinical pathway identification for translation of models to humans, scaffold material availability, and long-term biocompatibility need to be addressed prior to clinical realisation

High-pressure phases of FeTiO3 from first principles

Published versio

The Use of Platelet-Rich Plasma (PRP) for the Management of Non-union Fractures.

PURPOSE OF REVIEW: The treatment of non-union fractures represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have been investigated and utilised to support and improve bone healing. Among these agents, platelet-rich plasma (PRP) is an emerging strategy that is gaining popularity. The aim of this review is to evaluate the current literature regarding the application and clinical effectiveness of PRP injections, specifically for the treatment of non-union fractures. RECENT FINDINGS: The majority of published studies reported that PRP accelerated fracture healing; however, this evidence was predominantly level IV. The lack of randomised, clinical trials (level I-II evidence) is currently hampering the successful clinical translation of PRP as a therapy for non-union fractures. This is despite the positive reports regarding its potential to heal non-union fractures, when used in isolation or in combination with other forms of treatment. Future recommendations to facilitate clinical translation and acceptance of PRP as a therapy include the need to investigate the effects of administering higher volumes of PRP (i.e. 5-20 mL) along with the requirement for more prolonged (> 11 months) randomised clinical trials

The biosocial event : responding to innovation in the life sciences

Innovation in the life sciences calls for reflection on how sociologies separate and relate life processes and social processes. To this end we introduce the concept of the ‘biosocial event’. Some life processes and social processes have more mutual relevance than others. Some of these relationships are more negotiable than others. We show that levels of relevance and negotiability are not static but can change within existing relationships. Such changes, or biosocial events, lie at the heart of much unplanned biosocial novelty and much deliberate innovation. We illustrate and explore the concept through two examples – meningitis infection and epidemic, and the use of sonic ‘teen deterrents’ in urban settings. We then consider its value in developing sociological practice oriented to critically constructive engagement with innovation in the life sciences

Pitch Enumeration: Failure to Subitize in Audition

Background: Subitizing involves recognition mechanisms that allow effortless enumeration of up to four visual objects, however despite ample resolution experimental data suggest that only one pitch can be reliably enumerated. This may be due to the grouping of tones according to harmonic relationships by recognition mechanisms prior to fine pitch processing. Poorer frequency resolution of auditory information available to recognition mechanisms may lead to unrelated tones being grouped, resulting in underestimation of pitch number. Methods, Results and Conclusion: We tested whether pitch enumeration is better for chords of full harmonic complex tones, where grouping errors are less likely, than for complexes with fewer and less accurately tuned harmonics. Chords of low familiarity were used to mitigate the possibility that participants would recognize the chord itself and simply recall the number of pitches. We found that accuracy of pitch enumeration was less than the visual system overall, and underestimation of pitch number increased for stimuli containing fewer harmonics. We conclude that harmonically related tones are first grouped at the poorer frequency resolution of the auditory nerve, leading to poor enumeration of more than one pitch