Carrier For Growth Factors Research Articles

Growth factor-loaded ovarian extracellular matrix hydrogels promote in vivo ovarian niche regeneration and enhance fertility in premature ovarian insufficiency preclinical models

Premature ovarian insufficiency (POI) means menopause before 40 years of age affecting about 1 % of women. Approaches based on cell therapy and the paracrine effects of stem cells or bioproducts such as platelet-rich plasma have been proposed, but concerns remain about undesired systemic effects, as well as the need to optimize delivery methods through bioengineering methods. This study explores the efficacy of decellularized bovine ovarian cortex extracellular matrix (OvaECM) hydrogels alone and as a growth factor (GF) carrier (OvaECM+GF) in a chemotherapy-induced POI murine model. In vitro assays showed a gradual release of GF from the OvaECM sustained for two weeks. Chemotherapy drastically reduced follicle numbers, but OvaECM+GF treatment restored pre-antral follicle development. Moreover, this treatment notably regenerated the ovarian microenvironment by increasing cell proliferation and microvessel density while reducing chemotherapy-induced apoptosis and fibrosis. Whole-ovary RNA sequencing and gene set enrichment analysis revealed an upregulation of regeneration-related genes and a downregulation of apoptotic pathways. The OvaECM+GF treatment also yielded significantly better outcomes following ovarian stimulation and in vitro fertilization. After two consecutive crossbreeding cycles, OvaECM+GF-treated mice showed normal reproductive function. This research showcases the biocompatibility and efficacy of OvaECM to reverse POI in mice, setting a foundation to explore innovative bioengineering-based POI therapies. Statement of significancePremature ovarian insufficiency (POI) affects about 1 % of women worldwide, causing early menopause before 40 years old. Current treatments alleviate symptoms but do not restore ovarian function. This study explores an innovative approach using ovarian cortex extracellular matrix hydrogels to deliver growth factors into the murine ovarian niche and reverse POI. In vitro release kinetic assays demonstrated a gradual and sustained release of growth factors. In a POI-induced mouse model, intraovarian injections of the hydrogel encapsulating growth factors restored pre-antral follicle development, increased cell proliferation, reduced apoptosis and fibrosis, and improved ovarian response and in vitro fertilization outcomes. Long-term benefits included larger litter sizes. This innovative technique shows promise in regenerating the ovarian environment and improving reproductive outcomes.

Biofunctionalized hydrogel composed of genipin-crosslinked gelatin/hyaluronic acid incorporated with lyophilized platelet-rich fibrin for segmental bone defect repair

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects.In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering.Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.

Enhanced bone formation of rat mandibular bone defects with collagen membranes loaded on bone morphogenetic protein-9

Background/purposeBone morphogenetic protein-9 (BMP-9) has demonstrated multiple advantages in promoting osteogenesis. Our previous findings have indicated that the use of an absorbable collagen membrane (ACM) as a carrier for growth factors is effective in stimulating bone regeneration. The objective of this study was to assess the synergistic impact of BMP-9 incorporated into ACM (ACM/BMP-9) on bone formation within rat mandibular bone defects. Materials and methodsCircular bone defects of critical size were surgically induced on both sides of the rat mandibular bone, with subsequent random allocation into distinct groups: control, ACM alone, and ACM loaded with low (0.5 μg) or high (2.0 μg) concentrations of BMP-9. We conducted real-time in vivo micro-computerized tomography scans at the baseline and at 2, 4, and 6 weeks, and measured the volume of newly formed bone (NFB), bone mineral density (BMD) of NFB, and the closure percentage of the NFB area. Histological and histomorphometric analyses were performed at 6 weeks. ResultsReal-time assessment revealed notably higher levels of bone volume, BMD, and closure percentage in the NFB area for the groups treated with ACM/BMP-9 compared to the control and ACM groups. Within the high concentration of BMP-9 group, the volume and BMD of NFB exhibited a significant increase at 6 weeks compared to baseline. Histological examination confirmed the existence of osteoblasts, osteocytes, and blood vessels within the NFB. ConclusionConsidering the limitations of this research, the real-time evaluation finding indicates that ACM/BMP-9 effectively promotes bone formation in critical-size mandibular defects in rats.

Variability of BMP-2 content in DBM products derived from different long bone.

Demineralized bone matrix (DBM) has been regarded as an ideal bone substitute as a native carrier of bone morphogenetic proteins (BMPs) and other growth factors. However, the osteoinductive properties diverse in different DBM products. We speculate that the harvest origin further contributing to variability of BMPs contents in DBM products besides the process technology. In the study, the cortical bone of femur, tibia, humerus, and ulna from a signal donor were prepared and followed demineralizd into DBM products. Proteins in bone martix were extracted using guanidine-HCl and collagenase, respectively, and BMP-2 content was detected by sandwich enzyme-linked immunosorbent assay (ELISA). Variability of BMP-2 content was found in 4 different DBM products. By guanidine-HCl extraction, the average concentration in DBMs harvested from ulna, humerus, tibia, and femur were 0.613 ± 0.053, 0.848 ± 0.051, 3.293 ± 0.268, and 21.763 ± 0.344, respectively (p < 0.05), while using collagenase, the levels were 0.089 ± 0.004, 0.097 ± 0.004, 0.330 ± 0.012, and 1.562 ± 0.008, respectively (p < 0.05). In general, the content of BMP-2 in long bones of Lower limb was higher than that in long bones of upper limb, and GuHCl had remarkably superior extracted efficiency for BMP-2 compared to collagenase. The results suggest that the origin of cortical bones harvested to fabricate DBM products contribute to the variability of native BMP-2 content, while the protein extracted method only changes the measured values of BMP-2.

Ciliary neurotrophic factor mediated growth of retinal ganglion cell axons on PGS/PCL scaffolds

Ciliary neurotrophic factor (CNTF) promotes survival and/or differentiation of a variety of neuronal cells including retinal ganglion cells (RGCs). Delivery of CNTF requires a suitable medium capable of mediating diffusion and premature release of CNTF within the target tissue. Polymeric tissue-engineered scaffolds have been readily used as substrates for cell transplantation, expansion, and differentiation and, as carriers of cell growth factors. Their functions to CNTF release for RGC proliferation have remained so far unexplored, especially to CNTF affinity to the scaffold and subsequent RGC fate. Electrospun poly(glycerol sebacate)/poly(ϵ-caprolactone) (PGS/PCL) biopolymer scaffolds have recently shown promising results in terms of supporting regeneration of RGC neurites. This work explores covalent immobilization of CNTF on PGS/PCL scaffold and the way immobilised CNTF mediates growth of RGC axons on the scaffold. An ex-vivo three-dimensional model of rodent optic nerve on PGS/PCL revealed that RGC explants cultured in CNTF mediated environment increased their neurite extensions after 20 d of cell culture employing neurite outgrowth measurements. The CNTF secretion on PGS/PCL scaffold was found bio-mimicking natural extracellular matrix of the cell target tissue and, consequently, has shown a potential to improve the overall efficacy of the RGC regeneration process.

Bone regeneration using activin A/BMP2 chimera (AB204) with collagen membrane in rats with calvarial defects.

Collagen has long been recognized as an excellent carrier for growth factors, and membrane-type collagen has been widely applied in dentistry for guided bone regeneration. This study was conducted to examine the effects of an activin A/BMP2 chimera (AB204) combined with a collagen membrane (CM) on bone repair in a rat calvarial defect model. A unilateral calvarial defect measuring 5.0 mm was surgically created in 32 Sprague-Dawley rats. The rats were then randomly assigned to 1 of 4 groups, each consisting of 8 animals: control (untreated), CM (treated with a CM only), CM/bone morphogenetic protein 2 (BMP2) (treated with a CM and 1.0 μg of BMP2), and CM/AB204 (treated with a CM and 1.0 μg of AB204). Bone regeneration was evaluated using micro-computed tomography (CT) and histological analysis at 2 and 4 weeks following surgery. Micro-CT analysis revealed that bone formation in the CM/BMP2 and CM/AB204 groups was superior to that observed in the control and CM groups at both 2 and 4 weeks postoperatively. BMP2 induced greater bone regeneration than AB204 at 2 weeks; however, AB204 resulted in a greater bone volume at 4 weeks, achieving the highest values recorded. No significant differences were found between the CM/BMP2 and CM/AB204 groups at either time point (P>0.05). On histological examination, new bone formation was evident in both CM/BMP2 and CM/AB204 groups. Within the limitations of this study, the findings indicate that AB204 may enhance osteogenic potential when used in combination with CM for bone regeneration.

Cartilage regeneration using transforming growth factor-beta 3-loaded injectable crosslinked hyaluronic acid hydrogel.

Cartilage defects can be difficult to heal, potentially leading to complications such as osteoarthritis. Recently, a tissue engineering approach that uses scaffolds and growth factors has been proposed to regenerate new cartilage tissues. Herein, we investigated the application of hyaluronic acid (HA) gel loaded with transforming growth factor-beta 3 (TGF-β3) for enhanced cartilage regeneration. We assessed the clinical conditions required to efficiently enhance the ability of the modified HA gel to repair defective cartilage. Based on our findings, the prepared HA gel exhibited good physicochemical and mechanical properties and was non-toxic and non-inflammatory. Moreover, HA gel-loaded TGF-β3 (HAT) had improved biocompatibility and promoted the synthesis of cartilage-specific matrix and collagen, further improving its ability to repair defects. The application of HAT resulted in an initial burst release of HA, which degraded slowly in vivo. Finally, HAT combined with microfracture-inducing bone marrow stem cells could significantly improve the cartilage microenvironment and regeneration of cartilage defects. Our results indicate that HA is a suitable material for developing growth factor carriers, whereas HAT is a promising candidate for cartilage regeneration. Furthermore, this differentiated strategy provides a rapid and effective clinical approach for next-generation cartilage regeneration.

Berberine-Encapsulated Poly(lactic-co-glycolic acid)-Hydroxyapatite (PLGA/HA) Microspheres Synergistically Promote Bone Regeneration with DOPA-IGF-1 via the IGF-1R/PI3K/AKT/mTOR Pathway.

Polymer microspheres have recently shown outstanding potential for bone tissue engineering due to their large specific surface area, good porosity, injectable property, good biocompatibility, and biodegradability. Their good load-release function and surface modifiability make them useful as a carrier of drugs or growth factors for the repair of bone defects in irregularly injured or complex microenvironments, such as skull defects. In this study, berberine (BBR)-encapsulated poly(lactic-co-glycolic acid) (PLGA)/hydroxyapatite (HA) microspheres were fabricated using electrified liquid jets and a phase-separation technique, followed by modification with the 3,4-hydroxyphenalyalanine-containing recombinant insulin-like growth-factor-1 (DOPA-IGF-1). Both the BBR and the IGF-1 exhibited sustained release from the IGF-1@PLGA/HA-BBR microspheres, and the composite microspheres exhibited good biocompatibility. The results of the alkaline phosphatase (ALP) activity assays showed that the BBR and IGF-1 in the composite microspheres synergistically promoted the osteogenic differentiation of MC3T3-E1 cells. Furthermore, it was confirmed that immobilized IGF-1 enhances the mRNA expression of an osteogenic-related extracellular matrix and that BBR accelerates the mRNA expression of IGF-1-mediated osteogenic differentiation and cell mineralization. Further cellular studies demonstrate that IGF-1 could further synergistically activate the IGF-1R/PI3K/AKT/mTOR pathway using BBR, thereby enhancing IGF-1-mediated osteogenesis. Rat calvarial defect repair experiments show that IGF-1@PLGA/HA-BBR microspheres can effectively promote the complete bony connection required to cover the defect site and enhance bone defect repair. These findings suggest that IGF-1@PLGA/HA-BBR composite microspheres show a great potential for bone regeneration.

Combination Effect of Collagen-Chitosan Hydrogel and Injectable Platelet-Rich Fibrin Fractionation on Osteoblast Migration and Proliferation

Injectable Platelet Rich Fibrin (i-PRF) is a popular periodontal regenerative therapy in dentistry. i-PRF centrifugation resulted in the fractionation of the yellow layer and buffy coat with a red layer. The red i-PRF contains a greater number of Growth Factor carrier cells than yellow layer, besides that liquid-PRF has a suitable consistency so it easy to combine with other biomaterials. Another biomaterial that can be combined with i-PRF is collagen-chitosan with hydrogel preparations. This study aims to determine the effect of a combination of collagen-chitosan hydrogel formulation with injection of platelet-rich fibrin fractionation on osteoblast cell migration and proliferation. This type of research was an experimental laboratory divided into 3 groups, which were given a combination of the collagen-chitosan hydrogel and i-PRF red layer, a combination of collagen-chitosan hydrogel and i-PRF yellow layer, and only a combination of collagen-chitosan hydrogel. Chitosan collagen hydrogel was prepared with a collagen/chitosan ratio of 25/75, then mixed with i-PRF fractionation with a ratio of 1:1. The cell proliferation test used CCK-8, while the cell migration test used scratch wound healing. Data were tested with One way ANOVA for cell migration and Two way ANOVA for cell proliferation, followed by a Post Hoc test. The results showed that migration of osteoblast cells after 24 hours in the combination group of chitosan collagen hydrogel and i-PRF red layer was higher than the other groups with significance (p&lt;0.05). The results of osteoblast cell proliferation on days 1, 3, and 5 in the combination group of chitosan collagen hydrogel and i-PRF red layer were also higher than the other groups with significance (p&lt;0.05). This study concluded that the combination of chitosan collagen hydrogel with injectable platelet-rich fibrin red layer had a more effect on increasing the migration and proliferation of osteoblast cells than the other groups.

Lyophilized Platelet-Rich Fibrin Exudate-Loaded Carboxymethyl Chitosan/GelMA Hydrogel for Efficient Bone Defect Repair.

Platelet-rich fibrin (PRF) is an autologous growth factor carrier that promotes bone tissue regeneration, but its effectiveness is restrained by poor storage capabilities, uncontrollable concentration of growth factors, unstable shape, etc. Herein, we developed a photocrosslinkable composite hydrogel by incorporating lyophilized PRF exudate (LPRFe) into the carboxymethyl chitosan methacryloyl (CMCSMA)/gelatin methacryloyl (GelMA) hydrogel to effectively solve the dilemma of PRF. The hydrogel possessed suitable physical properties and sustainable release ability of growth factors in LPRFe. The LPRFe-loaded hydrogel could improve the adhesion, proliferation, migration, and osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). Furthermore, the animal experiments demonstrated that the hydrogel possessed excellent biocompatibility and biodegradability, and the introduction of LPRFe in the hydrogel can effectively accelerate the bone healing process. Conclusively, the combination of LPRFe with CMCSMA/GelMA hydrogel may be a promising therapeutic approach for bone defects.

Cicatrization of Oncological Wounds by Autologous Fibrin Biopolymer Dressing Treatment: A Case Series

Introduction. Traditional therapies used to treat chronic wounds are often expensive and, in general, are not adequate to support healing. A promising alternative to conventional dressings is the autologous biopolymer FM, full of cytokines and growth factors that accelerate the healing process of wounds of various etiologies. Materials and Methods. The authors report 3 cases in which FM was used to treat chronic oncological wounds that had been conventionally treated for more than 6 months with no sign of healing. Results. Among the 3 reported cases, there was complete healing of 2 wounds. The other lesion did not heal, mainly due to the location (at the base of the skull). However, it significantly reduced its area, extension, and depth. No adverse effects or hypertrophic scar formation were recorded, and the patients reported an absence of pain from the second week of FM application. Conclusions. The proposed FM dressing approach was effective in healing and speeding up tissue regeneration. It can also be considered one of the most versatile delivery systems to the wound bed, as it is an excellent carrier of growth factors and leukocytes.

Calcium Orthophosphate (CaPO4)-Based Bioceramics: Preparation, Properties, and Applications

Various types of materials have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A short time later, such synthetic biomaterials were called bioceramics. Bioceramics can be prepared from diverse inorganic substances, but this review is limited to calcium orthophosphate (CaPO4)-based formulations only, due to its chemical similarity to mammalian bones and teeth. During the past 50 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the CaPO4-based implants would remain biologically stable once incorporated into the skeletal structure or whether they would be resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed, and such formulations became an integrated part of the tissue engineering approach. Now, CaPO4-based scaffolds are designed to induce bone formation and vascularization. These scaffolds are usually porous and harbor various biomolecules and/or cells. Therefore, current biomedical applications of CaPO4-based bioceramics include artificial bone grafts, bone augmentations, maxillofacial reconstruction, spinal fusion, and periodontal disease repairs, as well as bone fillers after tumor surgery. Prospective future applications comprise drug delivery and tissue engineering purposes because CaPO4 appear to be promising carriers of growth factors, bioactive peptides, and various types of cells.

A study on in vitro and in vivo bioactivity of silk fibroin / nano-hydroxyapatite / graphene oxide composite scaffolds with directional channels

As an important carrier of cells and growth factors, scaffold materials have attracted attention in bone tissue engineering, but how to construct materials with both component and structural advantages is still a challenge. In this study, silk fibroin (SF) / nano-hydroxyapatite (nHAp) / graphene oxide (GO) composite scaffolds with directional channels were prepared by directional temperature field freeze-drying technique. The characterization, morphology, degradation rate, biocompatibility and bioactivity of directed channel SF/nHAp/GO scaffolds were studied systematically. As a comparison, the series of studies were also conducted in SF scaffolds, SF/nHAp scaffolds and undirected SF/nHAp/GO scaffolds. The characterization results showed that the directed channel SF/nHAp/GO scaffolds had better connectivity, more suitable porosity, degradation rate for osteogenesis and ability to induce bone-like apatite. The cell compatibility results showed that the directed channel SF/nHAp/GO scaffolds were more beneficial to the adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs). And the expression of osteogenic genes was all up-regulated by RT-PCR. The in vivo experimental results showed that the directed channel SF/nHAp/GO scaffolds showed stronger biological activity and osseointegration ability. The composite scaffolds were non-toxic in vitro and in vivo. Therefore, this material may have great application potential in repairing bone tissue defects. It provides a meaningful reference for the further study of scaffold materials with directional channels such as dental and orthopedical repair materials from the material composition and structure design.

Dual effect of TAT functionalized DHAH lipid nanoparticles with neurotrophic factors in human BBB and microglia cultures

BackgroundNeurodegenerative diseases (NDs) are an accelerating global health problem. Nevertheless, the stronghold of the brain- the blood–brain barrier (BBB) prevents drug penetrance and dwindles effective treatments. Therefore, it is crucial to identify Trojan horse-like drug carriers that can effectively cross the blood–brain barrier and reach the brain tissue. We have previously developed polyunsaturated fatty acids (PUFA)-based nanostructured lipid carriers (NLC), namely DHAH-NLC. These carriers are modulated with BBB-permeating compounds such as chitosan (CS) and trans-activating transcriptional activator (TAT) from HIV-1 that can entrap neurotrophic factors (NTF) serving as nanocarriers for NDs treatment. Moreover, microglia are suggested as a key causative factor of the undergoing neuroinflammation of NDs. In this work, we used in vitro models to investigate whether DHAH-NLCs can enter the brain via the BBB and investigate the therapeutic effect of NTF-containing DHAH-NLC and DHAH-NLC itself on lipopolysaccharide-challenged microglia.MethodsWe employed human induced pluripotent stem cell-derived brain microvascular endothelial cells (BMECs) to capitalize on the in vivo-like TEER of this BBB model and quantitatively assessed the permeability of DHAH-NLCs. We also used the HMC3 microglia cell line to assess the therapeutic effect of NTF-containing DHAH-NLC upon LPS challenge.ResultsTAT-functionalized DHAH-NLCs successfully crossed the in vitro BBB model, which exhibited high transendothelial electrical resistance (TEER) values (≈3000 Ω*cm2). Specifically, the TAT-functionalized DHAH-NLCs showed a permeability of up to 0.4% of the dose. Furthermore, using human microglia (HMC3), we demonstrate that DHAH-NLCs successfully counteracted the inflammatory response in our cultures after LPS challenge. Moreover, the encapsulation of glial cell-derived neurotrophic factor (GNDF)-containing DHAH-NLCs (DHAH-NLC-GNDF) activated the Nrf2/HO-1 pathway, suggesting the triggering of the endogenous anti-oxidative system present in microglia.ConclusionsOverall, this work shows that the TAT-functionalized DHAH-NLCs can cross the BBB, modulate immune responses, and serve as cargo carriers for growth factors; thus, constituting an attractive and promising novel drug delivery approach for the transport of therapeutics through the BBB into the brain.

3D Fiber Reinforced Hydrogel Scaffolds by Melt Electrowriting and Gel Casting as a Hybrid Design for Wound Healing.

Emerging biomanufacturing technologies have revolutionized the field of tissue engineering by offering unprecedented possibilities. Over the past few years, new opportunities arose by combining traditional and novel fabrication techniques, shaping the hybrid designs in biofabrication. One of the potential application fields is skin tissue engineering, in which a combination of traditional principles of wound dressing with advanced biofabrication methods could yield more efficient therapies. In this study, a hybrid design of fiber-reinforced scaffolds combined with gel casting is developed and the efficiency for in vivo wound healing applications is assessed. For this purpose, 3D fiber meshes produced by melt electrowriting are selectively filled with photocrosslinkable gelatin hydrogel matrices loaded with different growth factor carrier microspheres. Additionally, the influence of the inclusion of inorganic bioactive glass particles within the composite fibrous mesh is evaluated. Qualitative evaluation of secondary wound healing criteria and histological analysis shows that hybrid scaffolds containing growth factors and bioactive glass enhances the healing process significantly, compared to the designs merely providing a fiber-reinforced bioactive hydrogel matrix as the wound dressing. This study aims to explore a new application area for melt electrowriting as a powerful tool in fabricating hybrid therapeutic designs for skin tissue engineering.

Scaffolds from medical grade chitosan: A good choice for 3D cultivation of mesenchymal stem cells.

Chitosan has high biocompatibility, supports proliferation of many cells, and can be a good carrier for various growth factors. However, low attachment ratio and spheroid formation of several stem cell types on plain chitosan scaffolds/films is still a problem. In this study, it was aimed to obtain 3D scaffolds using medical grade chitosan (MC) with a high deacetylation degree (DD ≥ 92.6%) to overcome the spheroid formation of rat adipose tissue derived mesenchymal stem cells (rAdMSCs) on control chitosan (C, DD = 75%-85%) scaffolds. Genipin was used as a biological chemical crosslinker, and glycerol phosphate salt was used both as a pH adjusting agent and physical crosslinker. MTT and SEM analyses and live/dead staining indicated the increase in the attachment, cell viability, and proliferation of rAdMSCs on MC scaffolds with or without crosslinking when compared to the cells in spheroid formation on control scaffolds. Moreover, filamentous actin protein organization of rAdMSCs was found to be triggered on the crosslinked MC scaffolds. In conclusion, plain medical grade chitosan scaffolds with or without crosslinking prevented spheroid formation, supported the attachment, proliferation, and organization of rAdMSCs indicating that medical grade type of chitosan scaffolds with high DD can be a very good candidate as 3D carriers in stem cell cultivation.

From Blood to Regenerative Tissue: How Autologous Platelet-Rich Fibrin Can Be Combined with Other Materials to Ensure Controlled Drug and Growth Factor Release.

The purpose of this review is to examine the latest literature on the use of autologous platelet-rich fibrin as a drug and growth factor carrier system in maxillofacial surgery. Autologous platelet-rich fibrin (PRF) is a unique system that combines properties such as biocompatibility and biodegradability, in addition to containing growth factors and peptides that provide tissue regeneration. This opens up new horizons for the use of all beneficial ingredients in the blood sample for biomedical purposes. By itself, PRF has an unstable effect on osteogenesis: therefore, advanced approaches, including the combination of PRF with materials or drugs, are of great interest in clinics. The main advantage of drug delivery systems is that by controlling drug release, high drug concentrations locally and fewer side effects within other tissue can be achieved. This is especially important in tissues with limited blood supply, such as bone tissue compared to soft tissue. The ability of PRF to degrade naturally is considered an advantage for its use as a “warehouse” of controlled drug release systems. We are focusing on this concentrate, as it is easy to use in manipulations and can be delivered directly to the surgical site. The target audience for this review are researchers and medical doctors who are involved in the development and research of PRFs further studies. Likewise, surgeons who use PRF in their work to treat patients and who advice patients to take the medicine orally.

Comparison of demineralized bone matrix and hydroxyapatite as carriers of Escherichia coli recombinant human BMP-2

BackgroundAutograft has been widely used in various orthopedic and dental surgery for its superior osteogenicity, osteoinductivity and osteoconductivity. But the available volume of the autograft is limited and the efficacy of it is highly affected by the condition of the patients. Therefore, growth factors such as Escherichia coli bone morphogenetic protein-2 (ErhBMP-2) has been widely used in some countries and regions with various carriers that could affect the effects of the growth factors. Demineralized bone matrix (DBM) has been widely used as a bone graft substitute and growth factor carrier, but its effect as a carrier of ErhBMP-2 was less investigated.Materials and methodsRat calvaria defect model was used in this study. We implanted ErhBMP-2 with DBM or hydroxyapatite (HA) as a carrier in 8 mm calvaria defect and compared their bone regeneration effect in 4th week and 8th week after implantation with micro-CT and histology. The data was analyzed with one-way ANOVA method with Bonferroni post-hoc analysis.ResultThe group with DBM as the carrier showed significantly higher bone volume and bone thickness than the groups with HA as the carrier in both weeks. And the histology sections showed less adipose tissue formed in the groups with DBM as the carrier.ConclusionDBM could be a better carrier for ErhBMP-2 than HA.

Liposomes embedded with differentiating factors as a new strategy for enhancing DPSC osteogenic commitment.

Human dental pulp stem cell (DPSC) differentiation toward the osteoblastic phenotype is enhanced when culture media are supplemented with differentiating factors, i.e. ascorbic acid, β-glycerophosphate and dexamethasone. Liposomes, spherical vesicles formed by a phospholipid bilayer, are frequently used as carriers for drugs, growth factors and hydrophobic molecules. The aim of this work was to speed up DPSC commitment to the osteogenic lineage by embedding differentiating factors within liposomes. Firstly, liposomes were prepared by rehydrating a phospholipidic thin film and characterised in terms of dimensions. Secondly, liposome-exposed DPSCs were characterised by their immunophenotypic profile. Levels of CD90 were significantly decreased in the presence of liposomes filled with ascorbic acid, β-glycerophosphate and dexamethasone (Lipo-Mix) with respect to normal differentiation medium (DM), while CD73 and CD29 expression were enhanced, suggesting osteogenic commitment. Additionally, an appreciable extracellular matrix deposition is detected. Thirdly, the Lipo-Mix formulation better increases alkaline phosphatase activity and levels of Collagen I secretion with respect to DM. In parallel, the new liposome formulation is capable of decreasing the release of H2O2 and of triggering a precocious antioxidant cell response, redressing the redox balance required upon mesenchymal stem cell commitment to osteogenesis. It can be therefore hypothesised that Lipo-Mix could represent a suitable tool for clinical regenerative purposes in the field of tissue engineering by speeding up DPSC osteogenic commitment, mineralised matrix deposition and remodelling.

A Multiphysics Model for Bone Repair Using Magnetic Scaffolds for Targeted Drug Delivery

Magnetic bone substitutes are multifunctional nanocomposite biomaterials designed to serve as an in situ attraction platform for magnetic carriers of growth factors. The morphological and functional properties of these biomaterials were characterized so far, but very little is known on the treatment dynamics, and the latter cannot be designed from an engineering point of view. For the first time, this work deals with the mathematical modeling of the use of magnetic scaffolds and functionalized nanoparticles to evaluate the enhancement of osteogenesis and bone repair. The non-linear magnetization of the scaffolds is considered to simulate the attraction and transport of magnetic nanoparticles. Different biomaterials and drug carriers from the literature are analyzed. The drug release via RF-heating is modeled considering the multiphysics nature of the phenomena. The physiological process of bone healing is reproduced using nine non-linear equations. The influence of the delivered growth factor on osteogenesis is assessed and quantified in silico, while compared to numerical simulations of intravenous injection of growth factor and to its release from the biomaterial.The exploitation of magnetic carriers of biomolecules with magnetic scaffolds allows to produce a more homogeneous and uniform distribution of mature bone, overcoming the limitation of traditional drug delivery techniques