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Abstract Mesenchymal stem cells are core to bone homeostasis and repair. They both provide the progenitor cells from which bone cells are formed and regulate the local cytokine environment to create a pro-osteogenic environment. Dysregulation of these cells is often seen in orthopaedic pathology and can be manipulated by the physician treating the patient. This narrative review aims to describe the common applications of cell therapies to bone healing whilst also suggesting the future direction of these techniques.

Background: Metabolic reprogramming is one of the hallmarks of cancer, and in breast cancer (BC), several metabolic enzymes are overexpressed and overactivated. One of these, Enolase 1 (ENO1), catalyses glycolysis and is involved in the regulation of multiple signalling pathways. Objectives: This study aimed to evaluate in silico the prognostic and predictive effects of ENO1 expression in BC. Design: This is a bioinformatic in silico analysis. Methods: Using available online platforms (Kaplan–Meier [KM] plotter, receiver operating characteristic curve [ROC] plotter, cBioPortal, Genotype-2-Outcome [G-2-O], MethSurv, and Tumour–Immune System Interaction Database [TISIDB]), we performed a bioinformatic in silico analysis to establish the prognostic and predictive effects related to ENO1 expression in BC. A network analysis was performed using the Oncomine platform, and signalling, epigenetic, and immune regulation pathways were explored. Results: ENO1 was overexpressed in all the analysed Oncomine, epigenetic, and immune pathways in triple-negative, but not in hormone receptor–positive BCs. In human epidermal growth factor receptor 2 (HER2)-positive BCs, ENO1 expression showed a mixed profile. Analysis on disease progression and histological types showed ENO1 overexpression in ductal in situ and invasive carcinoma, in high-grade tumours followed by advanced or metastasis and was linked to worse survival. High ENO1 expression was also associated with relapse-free, distant metastasis-free and overall survival, irrespectively of treatment and was mainly related to basal subtype. Conclusion: ENO1 overexpression recruits a range of signalling pathways during disease progression conferring a worse prognosis and can be potentially used as a biomarker of disease progression and therapeutic target, particularly in triple-negative and in ductal invasive carcinoma.

The restoration of critical-size load-bearing bone defects calls for the application of bioactive scaffolds that are regenerative, osteoconductive, and demonstrate mechanical strength comparable with natural bone. Novel hydroxyapatite (HAp) scaffolds sourced and fabricated through the biomorphic transformation of rattan wood (GreenBone-GB) were laser-drilled (LD) with parallel and lateral sub-millimetre channels, which enhanced the overall porosity for promoting the flow of cells and fluids throughout the scaffolds. The compositional analysis of the LD scaffolds confirmed the presence of the Ca5(PO4)3OH and Ca3(PO4)2 phases, with no evidence of drilling contamination. Water jet laser drilling enhanced the interconnecting porosity of the morphogenic scaffolds by 22.5 %, without obstructing the intrinsic uniaxial fibrous structure inherited from rattan wood. Across eight varied drilled patterns, the resulting scaffolds preserved the structural integrity and exhibited compressive strength ranging from 6.74 ± 1.25 to 10.18 ± 0.43 MPa, while the Vickers Hardness was comparable with natural bone. Cell viability assessments confirmed that the LD scaffolds exhibited no toxicity and presented >90 % cell viability. We demonstrate that laser drilling effectively enhanced the pore volume for improved osteoconductivity via cell migration in the bio-morphogenic GB-structure. Since the GB scaffolds are CE-marked products, laser drilling for pore surface engineering could provide improved scaffolds for clinical use.

Abstract. The immune system plays an integral role in the regulation of cellular processes responsible for fracture healing. Local and systemic influences on fracture healing correlate in many ways with fracture-related outcomes, including soft tissue healing quality and fracture union rates. Impaired soft tissue healing, restricted perfusion of a fracture site, and infection also in turn affect the immune response to fracture injury. Modern techniques used to investigate the relationship between immune system function and fracture healing include precision medicine, using vast quantities of data to interpret broad patterns of inflammatory response. Early data from the PRECISE trial have demonstrated distinct patterns of inflammatory response in polytrauma patients, which thereby directly and indirectly regulate the fracture healing response. The clearly demonstrated linkage between immune function and fracture healing suggests that modulation of immune function has significant potential as a therapeutic target that can be used to enhance fracture healing.

Chitosan (CS), a biopolymer, holds significant potential in bone regeneration due to its biocompatibility and biodegradability attributes. While crustacean-derived CS is conventionally used in research, there is growing interest in fungal-derived CS for its equally potent properties in bone regenerative applications. Here, we investigated the physicochemical and biological characteristics of fungal (MDC) and crustacean (ADC)-derived CS scaffolds embedded with different concentrations of tricalcium phosphate minerals (TCP), i.e., 0(wt)%: ADC/MDC-1, 10(wt)%: ADC/MDC-2, 20(wt)%: ADC/MDC-3 and 30(wt)%: ADC/MDC-4. ADC-1 and MDC-1 lyophilised scaffolds lacking TCP minerals presented the highest zeta potentials of 47.3 ± 1.2 mV and 55.1 ± 1.6 mV, respectively. Scanning electron microscopy revealed prominent distinctions whereby MDC scaffolds exhibited striation-like structural microarchitecture in contrast to the porous morphology exhibited by ADC scaffold types. With regard to the 4-week scaffold mass reductions, MDC-1, MDC-2, MDC-3, and MDC-4 indicated declines of 55.98 ± 4.2%, 40.16 ± 3.6%, 27.05 ± 4.7%, and 19.16 ± 5.3%, respectively. Conversely, ADC-1, ADC-2, ADC-3, and ADC-4 presented mass reductions of 35.78 ± 5.1%, 25.19 ± 4.2%, 20.23 ± 6.3%, and 13.68 ± 5.4%, respectively. The biological performance of the scaffolds was assessed through in vitro bone marrow mesenchymal stromal cell (BMMSCs) attachment via indirect and direct cytotoxicity studies, where all scaffold types presented no cytotoxic behaviours. MDC scaffolds indicated results comparable to ADC, where both CS types exhibited similar physiochemical properties. Our data suggest that MDC scaffolds could be a potent alternative to ADC-derived scaffolds for bone regeneration applications, particularly for 10(wt)% TCP concentrations.

Biodegradable scaffolds are needed to repair bone defects. To promote the resorption of scaffolds, a large surface area is required to encourage neo-osteogenesis. Herein, we describe the synthesis and freeze-drying methodologies of ferric-ion (Fe3+) doped Dicalcium Phosphate Dihydrate mineral (DCPD), also known as brushite, which has been known to favour the in situ condition for osteogenesis. In this investigation, the role of chitosan during the synthesis of DCPD was explored to enhance the antimicrobial, scaffold pore distribution, and mechanical properties post freeze-drying. During the synthesis of DCPD, the calcium nitrate solution was hydrolysed with a predetermined stoichiometric concentration of ammonium phosphate. During the hydrolysis reaction, 10 (mol)% iron (Fe3+) nitrate (Fe(NO3)3) was incorporated, and the DCPD minerals were precipitated (Fe3+-DCPD). Chitosan stir-mixed with Fe3+-DCPD minerals was freeze-dried to create scaffolds. The structural, microstructural, and mechanical properties of freeze-dried materials were characterized.