Enhance Bone Regeneration Research Articles

Enhancing Bone Regeneration and Osteogenic Quality by n-HA Internalized Osteoblasts Synergized with ON Protein: Mechanistic Insights.

Bone scaffolds offer hope for oral jawbone repair, yet improving their osteogenic performance remains a clinical challenge. This study investigates a novel approach to enhance early bone formation and osteogenic quality by coloading hydroxyapatite (HA)─internalized osteoblasts (OHA) and osteonectin (ON) onto various scaffolds. Our findings demonstrated that the OHA could effectively facilitate the early bone regeneration by providing rapid calcium and phosphorus ion release via lysosome-mediated HA degradation, while the ON protein helps in ion deposition, cell proliferation, and matrix mineralization. When the PHA (PCL+HA) scaffold was incorporated with both the OHA and ON, the scaffold exhibited superior pro-osteogenic performance, driven by synergistic effects of rapid ion release from the OHA, slow ion release from the PHA, and upregulation of osteogenesis-related genes. The analyses of mechanisms revealed that the OHA activated MAPK and PI3K-Akt pathways, while ON stimulated calcium and Wnt signaling, collectively promoting the osteogenic potential. The strategy presented in this study paves a promising way for the development of advanced bone scaffolds to improve the bone regeneration quality.

MOF-Based Guided Bone Regeneration Membrane for Promoting Osteogenesis by Regulating Bone Microenvironment through Cascade Effects.

Regulation of bone microenvironment (BME) including innate pH values and metal ions affects cellular functions and activities of osteoblasts and osteoclasts, thereby significantly influencing the process of bone regeneration. How to achieve multiple effective regulations of the BME through cascade effects via facile material design and fabrication to significantly facilitate osteogenesis remains a challenge. Herein, a facilely-designed resorbable guided bone regeneration membrane (PCL/DEX@Ca-Zol) based on a drug-loaded metal-organic framework is reported. Thereinto, calcium ions, zoledronic acid, and dexamethasone embedded in the membrane can be responsively released specifically inside bone defect in an acid-triggered manner to synergistically regulate BME by neutralization of pH value, enhancement of osteogenic differentiation and mineralization, and inhibition of osteoclasts in one-go. Along with polycaprolactone as a structural support in the membrane for bone regeneration with fully utilized components of the composite membrane material, enhances bone regeneration with minimized side effects is accordingly achieved with the assistance of effective modulation of BME through multiple cascade effects.

Enhancing bone regeneration and osseointegration using rhPTH(1-34) and dimeric R25CPTH(1-34) in an osteoporotic beagle model.

This study investigates the effects of two parathyroid hormone (PTH) analogs, rhPTH(1-34) and dimeric R25CPTH(1-34), on bone regeneration and osseointegration in a postmenopausal osteoporosis model using beagle dogs. Twelve osteoporotic female beagles were subjected to implant surgeries and assigned to one of three groups: control, rhPTH(1-34), or dimeric R25CPTH(1-34). Bone regeneration and osseointegration were evaluated after 10 weeks using micro-computed tomographic (micro-CT), histological analyses, and serum biochemical assays. Results showed that the rhPTH(1-34) group demonstrated superior improvements in bone mineral density, trabecular architecture, and osseointegration compared to controls, while the dimeric R25CPTH(1-34) group exhibited similar, though slightly less pronounced, anabolic effects. Histological and TRAP assays indicated both PTH analogs significantly enhanced bone regeneration, especially in artificially created bone defects. The findings suggest that both rhPTH(1-34) and dimeric R25CPTH(1-34) hold potential as therapeutic agents for promoting bone regeneration and improving osseointegration around implants in osteoporotic conditions, with implications for their use in bone-related pathologies and reconstructive surgeries.

A Composite Foam of Dermal Matrix-Demineralized Bone Matrix for Enhanced Bone Regeneration.

Allogenic demineralized bone matrix (DBM) is widely used for bone repair and regeneration due to its osteoinductivity and osteoconductivity. The present study utilized acellular dermis microfibers to improve the DBM's clinical handling properties and to enhance bone regeneration. Donated human cadaver skin was de-epidermized and decellularized to be acellular dermal matrix (ADM), which was further processed into microfibers. Donated human bone was micronized and partially demineralized (∼30% calcium removal) for optimal bone regeneration. A flexible ADM/DBM composite foam was fabricated with ADM microfibers and DBM particles. Structural analysis found that the ADM/DBM composite foam had proper porosity with interconnected micropores and rapid wettability, and good stability upon cyclic compressions, whereas cytotoxicity test, in vitro collagenase degradation, and rat subcutaneous implantation showed good biocompatibility and biodegradability. The composite foam, used for in vitro coculture, significantly increased the alkaline phosphatase activity of C2C12 cells and upregulated the expression of osteogenesis-related genes of human umbilical cord mesenchymal stem cells. Using the rat Φ8 mm calvarium defect repair model, the ADM/DBM composite foam demonstrated superior osteogenicity by rapidly inducing new bone formation and achieving complete closure of the bone defects, as compared with the commercially available bone graft for skull repair (SkuHeal). Therefore, the ADM/DBM composite foam holds promise as a superior DBM-based product for repairing critical bone defects.

Synergistic Effects of Platelet-rich Fibrin and Photobiomodulation on Bone Regeneration in MC3T3-E1 Preosteoblasts

Platelet-rich fibrin (PRF) and Photobiomodulation (PBM) are established methods for promoting bone healing. PRF enhances cell proliferation and migration due to its rich concentration of growth factors, while PBM stimulates tissue repair through mitochondrial activation. Despite their efficacies, no in-depth studies have explored the synergistic effects of combining PRF and PBM. PRF was prepared at 50% and 100% concentrations, and PBM was applied using an 830 nm near-infrared laser at a dose of 5 J/cm². Cell viability, migration, and calcium deposition were assessed over seven and fourteen days. The combination of PRF and PBM significantly improved cell viability, migration, and calcium deposition, with the most notable effects observed after seven and fourteen days. However, a slight decrease in calcium deposition was noted in the 100% PRF combined with the PBM group, suggesting a potential feedback mechanism at higher PRF concentrations. This study is the first to explore the synergistic effects of PRF and PBM, offering new insights into optimizing bone tissue engineering strategies. The findings highlight the potential of this combined approach in enhancing bone regeneration, although further research is needed to refine the optimal conditions for these therapies.

Butea monosperma bark extract: a natural boost for osteogenesis via Wnt/β-catenin pathway activation in adipose-derived mesenchymal stem cells.

To investigate the impact of Butea monosperma (BM) bark extract on the osteogenic differentiation potential of rat adipose-derived mesenchymal stem cells (rADMSCs) and to elucidate the involvement of Wnt/β-catenin pathway in mediating this osseous effect. Characterizations (antioxidant assays, FTIR and LC/MS analyses) and docking studies (in silico) were performed to evaluate the presence of phytochemicals in the BM extract and their binding capacity to that of the frizzled receptor. rADMSCs were isolated and characterised for its differentiation potential of osteogenesis for stemness. Dose fixation, cytotoxicity, osteogenic differentiation (calcium, mineral deposition, alkaline phosphatase and osteocalcin) and gene expression (osteocalcin, Col1, osteonectin, Bmp2, Runx2, Wnt2, and β-catenin-14 and 28days) of the extract were also evaluated in vitro. FTIR and LC/MS analyses unveiled the phytochemicals in the extract and with docking studies confirmed their interaction with the frizzled receptor of Wnt/β-catenin pathway. rADMSCs were isolated and differentiated in the presence of the osteogenic induction medium. Dose fixation studies, cytotoxicity and cell viability assessments demonstrated the phytochemicals concentration-dependent cytotoxicity. The presence of specific bone markers highlighted the osteogenic differentiation potential of the phytochemicals. Furthermore, gene expression studies of rADMSCs depicted a heightened bone-forming capacity potentially facilitated by the activation of Wnt/β-catenin pathway. The phytochemicals of BM promoted the osteogenic differentiation of rADMSCs through the activation of the signalling Wnt/β-Catenin pathway, as evidenced by the significant upregulation of early and late bone markers. The phytochemicals may therefore be positioned as promising therapeutic agents for enhancing bone regeneration, offering new avenues for regenerative medicine.

3D-printing of dipyridamole/thermoplastic polyurethane materials for bone regeneration.

Tissue engineering combines biology and engineering to develop constructs for repairing or replacing damaged tissues. Over the last few years, this field has seen significant advancements, particularly in bone tissue engineering. 3D printing has revolutionised this field, allowing the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration, thus providing a personalised approach that offers unique control over the shape, size, and structure of 3D-printed constructs. Accordingly, thermoplastic polyurethane (TPU)-based 3D-printed scaffolds loaded with dipyridamole (DIP) were manufactured to evaluate their in vitro osteogenic capacity. The fabricated DIP-loaded TPU-based scaffolds were fully characterised, and their physical and mechanical properties analysed. Moreover, the DIP release profile, the biocompatibility of scaffolds with murine calvaria-derived pre-osteoblastic cells, and the intracellular alkaline phosphatase (ALP) assay to verify osteogenic ability were evaluated. The results suggested that these materials offered an attractive option for preparing bone scaffolds due to their mechanical properties. Indeed, the addition of DIP in concentrations up to 10% did not influence the compression modulus. Moreover, DIP-loaded scaffolds containing the highest DIP cargo (10% w/w) were able to provide sustained drug release for up to 30 days. Furthermore, cell viability, proliferation, and osteogenesis of MC3T3-E1 cells were significantly increased with the highest DIP cargo (10% w/w) compared to the control samples. These promising results suggest that DIP-loaded TPU-based scaffolds may enhance bone regeneration. Combined with the flexibility of 3D printing, this approach has the potential to enable the creation of customized scaffolds tailored to patients' needs at the point of care in the future.

Rosuvastatin/calcium carbonate co-precipitated nanoparticles: A novel synergistic approach enhancing local bone regeneration in osteoporotic rat model

This study aimed at preparing sustained release rosuvastatin (Ru) calcium carbonate (CC) co-precipitate nano-formulation for local intra-osseous application in osteoporotic rats. Nano-formulations were prepared by the co-precipitation method using different concentrations of polyvinyl alcohol (PVA) (0.2, 0.4, 0.6 %) as a stabilizer and equimolar ratios of calcium chloride and calcium carbonate (0.1, 0.3 or 0.5 M). Pre-formulation examination including; FTIR and X-ray diffraction confirmed the formation of CC nanoparticles in a crystalline structure that was preserved before and after loading with Ru. The optimized formula showing; PS of 105.71 ± 5.10 nm, PDI of 0.25 ± 0.02, ZP of −44.70 ± 0.09 mV, % EE of 60.16 ± 1.58 and a quasi-spherical nanoparticle with nano-deposition of Ru crystals adsorbed on them as seen under TEM and SEM, was then integrated in 20 % Pluronic gel. The Ru-gel exhibited good rheological behavior with a short gelation time of 20 sec and a sustained release pattern of 30 % for the optimized Ru/CC gel versus ≈ 90 % for the Ru/CC dispersion after 6 h. In-vivo, ovariectomy-induced osteoporotic rats were used to cause a bone defect in the tibial metaphysis. The drill-hole defects were then filled with the formulations under test and examined 30 days postoperatively. Through SEM-EDX scanning, histological assessments, and evaluation of bone metabolic markers, Ru/CC treatment significantly enhanced bone healing, improved bone microarchitecture, increased trabecular bone area, enhanced osteogenic gene expression, and reduced osteoclast activity. Experiments proved that Ru/CC successfully enhances osteogenesis and reduces osteoclastogenesis, proposing it as a promising therapeutic approach for enhancing bone regeneration in osteoporosis.

Strontium-Doped Whitlockite Scaffolds for Enhanced Bone Regeneration.

Bone graft substitutes to repair critical-sized bone fractures have experienced significant development over the last few decades. Among them, whitlockite (WH)-based bone grafts have proven to be effective in mediating bone healing. In the current study, a next generation, nature-inspired scaffold was developed with strontium-functionalized whitlockite nanoparticles (nSrWH) to enhance the intrinsic properties of WH. A series of nSrWH (with 2.5, 5, 7.5% Sr atomic substitution) were fabricated using a rapid-mixing wet precipitation route. Subsequently, the functionalized whitlockite was integrated into a gelatin-chondroitin sulfate scaffold and subjected to both in vitro and in vivo studies to investigate its osteogenic potential. Results indicated that nSrWH-containing scaffolds promoted osteogenic differentiation while inhibiting osteoclast activity. The positive impact of nSrWH was found to be dose-dependent, with the 7.5% Sr atomic substitution exhibiting the most significant results. Furthermore, the scaffold induced superior de novo bone regeneration compared to its undoped counterpart in the mouse calvarial critical-sized defect model. Collectively, these findings suggest that nSrWH nanoparticles inherit the beneficial properties of whitlockite, coupled by the therapeutic effects of Sr2+, operating in concert for an overall enhanced bone regeneration. As such, they constitute promising candidates to meet the biomedical requirements for bioactive bone graft substitutes.

3D Printing Hierarchical Porous Nanofibrous Scaffold for Bone Regeneration.

Current limitations in 3D printing pose significant challenges for the fabrication of hierarchical 3D scaffolds with nanofibrous structures that simulate the natural bone extracellular matrix (ECM) for enhanced bone regeneration. This study presents an innovative approach to 3D printing customized hierarchical porous scaffolds with nanofiber structures using biodegradable nanofibrous microspheres as the bio-ink. In vitro investigations demonstrate that the hierarchical porous architecture substantially enhances cell infiltration and proliferation rates, while the nanofiber topology provides physical cues to guide osteogenic differentiation and ECM deposition. When serving as a cell carrier, the 3D-printed nanofibrous scaffold promotes bone tissue regeneration and integration in vivo. Additionally, the facile and versatile chemical modification facilitates the precise tailoring of the scaffold's functionality. Using nanofibrous microspheres with highly biomimetic and versatile modification properties as the foundational constituent in this universal 3D printing methodology enables comprehensive manipulation of scaffolding biological properties, spanning from macroscopic external morphology to molecular-scale biochemical kinetics, thereby addressing a diverse spectrum of clinical requisites.

Antibacterial bioadaptive scaffold promotes vascularized bone regeneration by synergistical action of intrinsic stimulation and immunomodulatory activity

The coupling of angiogenesis and osteogenesis is the fundamental necessity in bone fracture healing, thus simulative action of tissue-engineered bone provides powerful and beneficial effects in the treatment of bone defect. Herein, an immunoregulatory biocomposite scaffold with intrinsic activities of coupling angiogenesis and osteogenesis was constructed based on polyelectrolytes-modified 3D-printed scaffold for enhanced bone regeneration. The doping of Sr-doped hydroxyapatite (SrHA) within 3D-printed polycaprolactone (PCL) scaffold and subsequent slit guidance ligand 3 (SLIT3) protein adsorption through surface coating of carboxymethyl chitosan (CCS)/hyperbranched polylysine (HBPL) achieved on-demand delivery of SLIT3 and Sr ions. The antibacterial property of polyelectrolytes-modified scaffold was characterized and was directly proportional to the layer number of polyelectrolytes coating. The dual-factor delivery scaffold had good biocompatibility to support cell proliferation and migration, and was capable of stimulating angiogenesis and osteogenesis by intrinsic stimulation from released SLIT3 protein and Sr ions. Importantly, the multifunctional scaffold had immunomodulatory effects of promoting M2-type polarization of macrophages and thereby increasing anti-inflammatory factors level, as well as indirectly promoting angiogenesis and osteogenesis. The in vivo experiments revealed that the anti-inflammatory effect was significantly reinforced for providing a better regenerative microenvironment and bone regeneration capacity was dramatically enhanced accompanied with type H vessels formation when implanted with multifunctional scaffold. Therefore, the bioadaptive scaffold possessed amplified bone regeneration performance through intrinsic stimulation and immunomodulatory effects, suggesting a promising therapeutic candidate for bone defect repair.

The Effect of Platelet-Rich Fibrin (PRF) in Accelerating Periodontal Regeneration: A Randomized Controlled Clinical Trial

ABSTRACT Background: Regeneration of periodontal tissues is an essential component in treating periodontal disease, and there is an increasing focus on biological agents that might improve the healing process. Materials and Methods: The randomized controlled clinical study included a cohort of 60 individuals diagnosed with chronic periodontitis. Each participant was randomly allocated to one of two groups: the experimental group (n = 30), which underwent PRF in combination with traditional open flap debridement (OFD), and the control group (n = 30), which received OFD alone. Clinical criteria such as probing pocket depth (PPD), clinical attachment level (CAL), and bone fill percentage were assessed at baseline and after 6 months. Furthermore, cone-beam computed tomography (CBCT) was used to evaluate bone regrowth radiographically. Results: Following a period of 6 months, the experimental group had a notable decrease in postpartum depression (mean decrease of 4.2 mm) and an increase in central artery ligation (mean increase of 3.5 mm) compared to the control group, which had a mean decrease in postpartum depression of 2.8 mm and a mean increase in central artery ligation of 2.1 mm. The test group had a notably greater proportion of bone fill (45%) in comparison to the control group (30%). Further radiographic study verified enhanced bone regeneration in the areas treated with PRF. Conclusion: The use of Platelet-Rich Fibrin (PRF) in combination with traditional periodontal surgery greatly expedites the process of periodontal regeneration, as shown by notable enhancements in clinical indicators and bone regeneration.

Dental Pulp Stem Cell Conditioned Medium Enhance Osteoblastic Differentiation and Bone Regeneration.

Cell-free approaches, utilizing mesenchymal stem cell secretome, have promising prospects in various fields of regenerative medicine. In this study, we examined in vitro and in vivo the potential of dental pulp stem cell-conditioned medium (DPSC-CM) for bone regeneration. The secretome of undifferentiated stem cells from dental pulp were collected, and the effects of this DPSC-CM were assessed for osteodifferentiation of osteoblast-like cells (MG-63) and osteoblasts deriving from DPSC. Cell proliferation, alkaline phosphatase (ALP) activity, gene expression of Runt-related transcription factor 2 (Runx2), Bone Sialoprotein (BSP), Osteocalcin (OCN), and extracellular matrix mineralization were evaluated. The rat caudal vertebrae critical size defect model was to investigate the effect of DPSC-CM in vivo. Results showed that DPSC-CM induced cell growth, and increased ALP activity and the expression of key marker genes at an early stage of osteoblastic differentiation compared to control. A rat bone defect model was used to illustrate the effect of DPSC-CM in vivo. The bone density within the defects were improved using conditioned medium, even though there was no significant difference between the control and DPSC-CM groups. The analysis of DPSC-CM by human growth factor antibody array revealed the presence of several factors involved in osteogenesis. Taken together, these findings indicate that DPSC-CM is a promising therapeutic candidate for bone regenerative therapy, accelerating the maturation of osteoblastic cells. And even though safety and efficiency of DPSC-CM have to be confirmed in preclinical studies, these results represent a first step toward clinical application.

Visible light-induced simultaneous bioactive amorphous calcium phosphate mineralization and in situ crosslinking of coacervate-based injectable underwater adhesive hydrogels for enhanced bone regeneration

The field of bone tissue engineering is vital due to increasing bone disorders and limitations of traditional grafts. Injectable hydrogels offer minimally invasive solutions but often lack mechanical integrity and biological functionality, including osteoinductive capacity and structural stability under physiological conditions. To address these issues, we propose a coacervate-based injectable adhesive hydrogel that utilizes the dual functionality of in situ photocrosslinking and osteoinductive amorphous calcium phosphate formation, both of which are activated simultaneously by visible light irradiation. The developed hydrogel formulation integrated a photoreactive agent with calcium ions and phosphonodiol in a matrix of tyramine-conjugated alginate and RGD peptide-fused bioengineered mussel adhesive protein, promoting rapid setting, robust underwater adhesion, and bioactive mineral deposition. The hydrogel also exhibited superior mechanical properties, including enhanced underwater tissue adhesive strength and compressive resistance. In vivo evaluation using a rat femoral tunnel defect model confirmed the efficacy of the developed adhesive hydrogel in facilitating easy application to irregularly shaped defects through injection, rapid bone regeneration without the addition of bone grafts, and integration within the defect sites. This injectable adhesive hydrogel system holds significant potential for advancing bone tissue engineering, providing a versatile, efficient, and biologically favorable alternative to conventional bone repair methodologies.

Effects of Aging on the Immune and Periosteal Response to Fracture in Mice.

Aging predisposes individuals to reduced bone mass and fragility fractures, which are costly and linked to high mortality. Understanding how aging affects fracture healing is essential for developing therapies to enhance bone regeneration in older adults. During the inflammatory phase of fracture healing, immune cells are recruited to the injury site as periosteal skeletal stem/progenitor cells (pSSPCs) rapidly proliferate and differentiate into osteochondral lineages, allowing for fibrocartilaginous callus formation and complete bone healing. Irrespective of age, how periosteal mesenchymal and immune cells interact during early fracture healing is incompletely understood, limiting our ability to potentially modulate these processes. To address this, we directly analyzed, in parallel, at a single-cell level, isolated murine CD45(+) and CD45(-) periosteal cells dissected from intact and fractured bones, collected three days after injury. Through comprehensive analysis, corroborated by bulk RNA-sequencing, flow cytometry, and histology, we found aging decreases pSSPCs proliferative, marked by a reduced expression of genes required for callus formation and an increased senescence signature. We found that the chemokine Cxcl9 was highly upregulated in aged intact Prrx1+ pSSPCs, predicted to interact with other pSSPCs directly, and associated with increased recruitment of CD8+ T cells at the fracture site three days after injury. Cell-to-cell communication analysis provided insight into the complexity of interactions among the many cell types regulating fracture healing and the impact of aging on these processes. Together, these results provide insight into age-induced alterations in fracture healing, informing the development of improved therapeutic approaches for fragility fractures.

A Review on Advances and Challenges in Core-Shell Scaffolds for Bone Tissue Engineering: Design, Fabrication, and Clinical Translation.

This review explores core-shell scaffolds in bone tissue engineering, highlighting their osteoconductive and osteoinductive properties critical for bone growth and regeneration. Key design factors include material selection, porosity, mechanical strength, biodegradation kinetics, and bioactivity. Electrospun core-shell nanofibrous scaffolds demonstrate potential in delivering therapeutic agents and enhancing bone regeneration. Critical characterization techniques include structural, surface, chemical composition, mechanical, and degradation analyses. Scaling up production poses challenges, addressed by innovative electrospinning techniques. Future research focuses on regulatory and commercial considerations, while exploring advanced materials and fabrication methods to optimize scaffold performance for improved clinical outcomes.

Electrospun Polylactic Acid/Polyethylene Glycol/ Silicate‐Chlorinated Bioactive Glass Composite Scaffolds for Potential Bone Regeneration

ABSTRACTThe integration of bioglass with polymers in tissue engineering scaffolds holds promise for enhancing bone regeneration. This study explores the fabrication and characterization of composite scaffolds comprising polylactic acid (PLA)/polyethylene glycol (PEG) fibers incorporated with silicate‐chlorinated bioglasses (45S5 and 58S). Electrospinning was utilized to produce the scaffolds, followed by physical–chemical and in vitro evaluations. Scanning electron microscopy (SEM) revealed uniform fiber formation, with bioglass incorporation observed in the composite groups. Bioglass incorporation led to a significant reduction in fiber diameter. Thermogravimetric analysis (TGA) estimated bioglass content, with 58S exhibiting the highest incorporation. Contact angle measurements indicated enhanced hydrophilicity in bioglass‐containing groups. In vitro, bioactivity assessment in simulated body fluid (SBF) demonstrated apatite formation potential and the pH variance indicates a slightly alkaline to neutral condition. Cell culture studies revealed robust cellular adhesion and metabolic activity across all groups, with no cytotoxic effects observed. Overall, these findings suggest the potential of PLA/PEG bioglass composite scaffolds for bone tissue engineering applications.

Enhanced bone tissue regeneration via mesenchymal stem cells-laden Alginate/GelMa 3D-Bioprinted scaffold treated with Haplophyllum tuberculatum extract

Background and aimRegeneration of critical-sized bone defects is challenging due to avascular necrosis, inflammation, and disrupted osteogenesis. This study explores the synergistic effects of Haplophyllum tuberculatum (HT) extract and mesenchymal stem cells (MSCs) in an Alg/GelMa 3D-bioprinted scaffold to enhance bone regeneration. MethodsEthanolic extracts of stems (HTS), flowers (HTF), and a mixture (HTM) were obtained via Soxhlet extraction and subsequently characterized. Further investigations into their cytotoxicity, osteogenic and bone tissue regeneration potential were conducted, in vitro and in vivo. ResultsAlongside GC-MS analysis, vitamin and elemental analyses of HTS, HTF, and HTM revealed varying concentrations of key elements essential for bone regeneration. All extracts exhibited moderate antioxidant activity, with more potency in the HTF group. Cytotoxicity assays indicated the lack of cytotoxic effects from HTS and HTF on MSCs. The calcium secretion and deposition on MSCs revealed the osteogenic potential of HTF and HTM. Gene and protein expression analyses indicated significant upregulation of osteogenic markers in HTF-treated MSCs. The integration of MSCs into a Alg/GelMa 3D-bioprinted scaffold enhanced their viability and proliferation, validating its biocompatibility. Additionally, HTF promoted calcium deposition and ALP activity in the MSC-laden 3D-bioprinted scaffold. In vivo assessment in a rat calvarial defect model, demonstrated accelerated bone regeneration with HTF-treated scaffolds. The improved bone regeneration, vascularization, and collagen formation in HTF-treated defects were confirmed by histopathology results. ConclusionThis study underscores the significant role of the HTF in promoting osteogenesis, advocating for its incorporation into advanced tissue engineering strategies for bone regeneration.

Development of Functionalized Poly(ε-caprolactone)/Hydroxyapatite Scaffolds via Electrospinning 3D for Enhanced Bone Regeneration.

Functionalized scaffolds based on biodegradable polymers are materials used in bone tissue engineering. This study presents the development of functionalized fibrous scaffolds, fabricated from poly(ε-caprolactone) (PCL) and hydroxyapatite (HA). To produce this material, a short-distance electrospinning (ES) system was developed by adapting a 3D printer. The morphology and chemical properties of the scaffolds were evaluated using scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The results confirmed the porous structure and the presence of hydroxyapatite throughout the entire scaffold area. Mechanical tests indicated good elasticity and tensile strength of the scaffolds, favorable for bone regeneration. In vitro tests showed high levels of cell viability. Furthermore, in vivo experiments using a calvarial defect model in rats demonstrated that the PCL/HA scaffold promoted enhanced bone regeneration. Therefore, the PCL/HA scaffold developed through the adapted electrospinning system shows promise for bone repair.

Bone Disease in Primary Hyperparathyroidism-Changes Occurring in Bone Metabolism and New Potential Treatment Strategies.

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, predominantly caused by a single parathyroid adenoma that is responsible for the excessive secretion of parathyroid hormone (PTH)-the hallmark of disease. Excess of this hormone causes remarkable changes in bone metabolism, including an increased level of bone remodeling with a predominance of bone resorption. Those changes lead to deterioration of bone structure and density, especially in cortical bone. The main treatment for PHPT is surgical removal of the adenoma, which normalizes PTH levels and terminates the progression of bone disease and leads to its regeneration. However, because not all the patients are suitable candidates for surgery, alternative therapies are needed. Current non-surgical treatments targeting bone disease secondary to PHPT include bisphosphonates and denosumab. Those antiresorptives prevent further bone loss, but they lack the ability to regenerate already degraded bone. There is ongoing research to find targeted drugs capable of halting resorption alongside stimulating bone formation. This review presents the advancements in understanding the molecular mechanisms responsible for bone disease in PHPT and assesses the efficacy of new potential therapeutic approaches (e.g., allosteric inhibitors of the PTH receptor, V-ATPase, or cathepsin inhibitors) aimed at mitigating bone loss and enhancing bone regeneration in affected patients.