Hard Tissue Regeneration Research Articles

Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering.

Three-dimensional bioprinting is a promising technology for bone tissue engineering. However, most hydrogel bioinks lack the mechanical and post-printing fidelity properties suitable for such hard tissue regeneration. To overcome these weak properties, calcium phosphates can be employed in a bioink to compensate for the lack of certain characteristics. Further, the extracellular matrix of natural bone contains this mineral, resulting in its structural robustness. Thus, calcium phosphates are necessary components of bioink for bone tissue engineering. This review paper examines different recently explored calcium phosphates, as a component of potential bioinks, for the biological, mechanical and structural properties required of 3D bioprinted scaffolds, exploring their distinctive properties that render them favorable biomaterials for bone tissue engineering. The discussion encompasses recent applications and adaptations of 3D-printed scaffolds built with calcium phosphates, delving into the scientific reasons behind the prevalence of certain types of calcium phosphates over others. Additionally, this paper elucidates their interactions with polymer hydrogels for 3D bioprinting applications. Overall, the current status of calcium phosphate/hydrogel bioinks for 3D bioprinting in bone tissue engineering has been investigated.

A novel bi-layered asymmetric membrane incorporating demineralized dentin matrix accelerates tissue healing and bone regeneration in a rat skull defect model.

Objectives: The technique of guided bone regeneration (GBR) has been widely used in the field of reconstructive dentistry to address hard tissue deficiency. The objective of this research was to manufacture a novel bi-layered asymmetric membrane that incorporates demineralized dentin matrix (DDM), a bioactive bone replacement derived from dentin, in order to achieve both soft tissue isolation and hard tissue regeneration simultaneously. Methods: DDM particles were harvested from healthy, caries-free permanent teeth. The electrospinning technique was utilized to synthesize bi-layered DDM-loaded PLGA/PLA (DPP) membranes. We analyzed the DPP bilayer membranes' surface topography, physicochemical properties and degradation ability. Rat skull critical size defects (CSDs) were constructed to investigate in vivo bone regeneration. Results: The synthesized DPP bilayer membranes possessed suitable surface characteristics, acceptable mechanical properties, good hydrophilicity, favorable apatite forming ability and suitable degradability. Micro-computed tomography (CT) showed significantly more new bone formation in the rat skull defects implanted with the DPP bilayer membranes. Histological evaluation further revealed that the bone was more mature with denser bone trabeculae. In addition, the DPP bilayer membrane significantly promoted the expression of the OCN matrix protein in vivo. Conclusions: The DPP bilayer membranes exhibited remarkable biological safety and osteogenic activity in vivo and showed potential as a prospective candidate for GBR applications in the future.

Dental Stem Cell-Derived Exosomes: A Review of Their Isolation, Classification, Functions, and Mechanisms.

The scientific field concerned with the study of regeneration has developed rapidly in recent years. Stem cell therapy is a highly promising therapeutic modality for repairing tissue defects; however, several limitations exist, such as cytotoxicity, potential immune rejection, and ethical issues. Exosomes secreted by stem cells are cell-specific secreted vesicles that play a regulatory role in many biological functions in the human body; they not only have a series of functional roles of stem cells and exert the expected therapeutic effects, but they can also overcome the mass limitations of stem cells and are thus considered in the research as an alternative treatment strategy for stem cells. Since dental stem cell-derived exosomes (DSC-Exos) are easy to acquire and present modulating effects in several fields, including neurovascular regeneration and craniofacial soft and hard tissue regeneration processes, they are served as an emerging cell-free therapeutic strategy in various systematic diseases. There is a growing body of research on various types of DSC-Exos; however, they lack systematic elaboration and tabular summarization. Therefore, this review presents the isolation, characterization, and phenotypes of DSC-Exos and focuses on their current status of functions and mechanisms, as well as the multiple challenges prior to clinical applications.

Tunable Release of Calcium from Chitosan-Coated Bioglass.

Bioglass presents a standard biomaterial for regeneration of hard tissues in orthopedics and dentistry. The notable osteo-inductive properties of bioglass are largely due to the release of calcium ions from it. However, this release is not easily controllable and can often be excessive, especially during the initial interaction of the biomaterial with the surrounding tissues. Consequently, this excessive release can deplete the calcium content of the bioglass, ultimately reducing its overall bioactivity. In this study, we have tested if applying biopolymer chitosan coatings of different thicknesses would be able to mitigate and regulate the calcium ion release from monodisperse bioglass nanoparticles. Calcium release was assessed for four different chitosan coating thicknesses at different time points over the period of 28 days using a fluorescence quencher. Expectedly, chitosan-coated particles released less calcium as the concentration of chitosan in the coating solution increased, presumably due to the increased thickness of the chitosan coating around the bioglass particles. The mechanism of release remained constant for each coating thickness, corresponding to anomalous, non-Fickian diffusion, but the degree of anomalousness increased with the deposition of chitosan. Zeta potential testing showed an expected increase in the positive double layer charge following the deposition of the chitosan coating due to the surface exposure of the amine groups of chitosan. Less intuitively, the zeta potential became less positive as thickness of the chitosan coating increased, attesting to the lower density of the surface charges within thicker coatings than within the thinner ones. Overall, the findings of this study demonstrate that chitosan coating efficiently prevents the early release of calcium from bioglass. This coating procedure also allows for the tuning of the calcium release kinetics by controlling the chitosan concentration in the parent solution.

Effect of Bioactive Glasses and Basic Fibroblast Growth Factor on Dental Pulp Cells.

Ideal regeneration of hard tissue and dental pulp has been reported with the use of a combination of bioactive glass and basic fibroblast growth factor (bFGF). However, no previous study has investigated the molecular mechanisms underlying the processes induced by this combination in dental pulp cells. This study aimed to examine the cellular phenotype and transcriptional changes induced by the combination of bioactive glass solution (BG) and bFGF in dental pulp cells using phase-contrast microscopy, a cell counting kit-8 assay, alkaline phosphatase staining, and RNA sequence analysis. bFGF induced elongation of the cell process and increased the number of cells. Whereas BG did not increase ALP activity, it induced extracellular matrix-related genes in the dental pulp. In addition, the combination of BG and bFGF induces gliogenesis-related genes in the nervous system. This is to say, bFGF increased the viability of dental pulp cells, bioactive glass induced odontogenesis, and a dual stimulation with bioactive glass and bFGF induced the wound healing of the nerve system in the dental pulp. Taken together, bioactive glass and bFGF may be useful for the regeneration of the dentin-pulp complex.

Targeting class A GPCRs for hard tissue regeneration

G protein-coupled receptors (GPCRs) play important roles in various pathogeneses and physiological regulations. Owing to their functional diversity, GPCRs are considered one of the primary pharmaceutical targets. However, drugs targeting GPCRs have not been developed yet to regenerate hard tissues such as teeth and bones. Mesenchymal stromal cells (MSCs) have high proliferation and multi-lineage differentiation potential, which are essential for hard tissue regeneration. Here, we present a strategy for targeting class A GPCRs for hard tissue regeneration by promoting the differentiation of endogenous MSCs into osteogenic and odontogenic progenitor cells. Through in vitro screening targeted at class A GPCRs, we identified six target receptors (LPAR1, F2R, F2RL1, F2RL2, S1PR1, and ADORA2A) and candidate drugs with potent biomineralization effects. Through a combination of profiling whole transcriptome and accessible chromatin regions, we identified that p53 acts as a key transcriptional activator of genes that modulate the biomineralization process. Moreover, the therapeutic potential of class A GPCR-targeting drugs was demonstrated in tooth pulpotomy and calvarial defect models. The selected drugs revealed potent regenerative effects in both tooth and bone defects, represented by newly formed highly mineralized regions. Consequently, this study provides translational evidence for a new regenerative strategy for damaged hard tissue.

Rapidly derived equimolar Ca: P phasic bioactive glass infused flexible gelatin multi-functional scaffolds – A promising tissue engineering

The study aims to design and fabricate an ultra-easier multi-functional biomedical polymeric scaffold loaded with unique equimolar Ca:P phasic bioactive glass material (BG). Gelatin (G) – 45S5 bioactive glass (BG) scaffolds were synthesized via a simple laboratory refrigerator with higher biocompatibility and cytocompatibility. The results proved that BG has enhanced bio-mineralization of the scaffolds and results support that the G: BG (1:2) ratio is the more appropriate composition. Brunauer-Emmett-Teller (BET) study confirms the higher surface area for pure Gelatin and G: BG (1:2). Scanning Electron Microscopic images display the precipitation of hydroxycarbonate apatite layer over the scaffolds on immersing it in simulated body fluid. Alkaline phosphate activity proved that G: BG (1:2) scaffold could induce mitogenesis in MG-63 osteoblast cells, thus helping in hard tissue regeneration. Sirius red collagen deposition showed that higher content bioactive glass incorporated Gelatin polymeric scaffold G: BG (1:2) could induce rapid collagen secretion of NIH 3T3 fibroblast cell line that could help in soft tissue regeneration and earlier wound healing. The scaffolds were also tested for cell viability using NIH 3T3 fibroblast cell lines and MG 63 osteoblastic cell lines through methyl thiazolyl tetrazolium (MTT) assay. Thus, the study shows a scaffold of appropriate composition G: BG (1:2) can be a multifunctional material to regenerate hard and soft tissues.

An “organic-inorganic” hybrid multilayer film for comprehensive support in soft and hard tissue regeneration after osteosarcoma resection

Three major complications often occur after osteosarcoma resection: large bone defects, infectious wounds, and tumor recurrence. In addition to conventional internal fixation and auto- or allografts, multifunctional supportive treatments are needed for limb reconstruction after tumor removal. With inspiration from the "organic-inorganic" hybrid concept, we developed a freestanding polyelectrolyte membrane (PEM) using a layer-by-layer (LBL) deposition of quaternized chitosan (QCS) and hyaluronic acid (HA), and with copper-doped laponite (CuLAP) intercalation. The CuLAP demonstrated photothermal conversion capabilities under near-infrared (NIR) light irradiation, and displayed glutathione (GSH)-depleted Fenton-like catalytic activity. The further engineered PEM possesses a "brick and mortar" structure with enhanced surface roughness and stiffness. The fusion of CuLAP-mediated GSH-depleted chemodynamic treatment (CDT) and moderate photothermal therapy (PTT) facilitated tumor ablation and bactericidal effects. Moreover, the continuous release of copper ions and silicates aided angiogenesis and osteogenesis, supporting the regeneration of both soft (skin) and hard (bone) tissues. This all-in-one platform offers a promising clinical tool for assisting tissue reconstruction after osteosarcoma resection.

Analysis of Alveolar Crest Reduction Post Extraction with the Use of Platelet Rich Fibrin (PRF)

One of the treatments that can be done to treat dental and oral diseases is tooth extraction. However, this procedure can cause significant changes in the dimensions of the alveolar ridge that are unfavorable in subsequent oral rehabilitation. One of the most important things is the preservation of the remaining alveolar ridge after the tooth extraction procedure. The use of Platelet Rich Fibrin (PRF) for the regeneration of soft and hard tissue in wound healing, in the form of immune concentrate and platelets obtained from a single fibrin membrane which contains all the blood constituents useful for healing and immunity. This research is an unblinded, randomized clinical trial with a sample size of 36 patients undergoing tooth extraction. To see the effect of ridge resorption analysis, namely the reduction of the alveolar crest with PRF application. Each research sample is analyzed at each evaluation time. There was a significant difference in alveolar crest reduction in the treatment and control groups which was found in the mesial region (post-extraction days 60 and 90) and distal region (post-extraction days 30, 60 and 90) with a significance value p<0.05. There was a significant difference in the periapical x-ray image in the reduction of the post-extraction alveolar crest in the PRF application group, with better results compared to the group without PRF.

Enhancement of properties of a cell-laden GelMA hydrogel-based bioink via calcium phosphate phase transition

To improve the properties of the hydrogel-based bioinks, a calcium phosphate phase transition was applied, and the products were examined. We successfully enhanced the mechanical properties of the hydrogels by adding small amounts (< 0.5 wt%) of alpha-tricalcium phosphate (α-TCP) to photo-crosslinkable gelatin methacrylate (GelMA). As a result of the hydrolyzing calcium phosphate phase transition involving α-TCP, which proceeded for 36 h in the cell culture medium, calcium-deficient hydroxyapatite was produced. Approximately 18 times the compressive modulus was achieved for GelMA with 0.5 wt% α-TCP (20.96 kPa) compared with pure GelMA (1.18 kPa). Although cell proliferation decreased during the early stages of cultivation, both osteogenic differentiation and mineralization activities increased dramatically when the calcium phosphate phase transition was performed with 0.25 wt% α-TCP. The addition of α-TCP improved the printability and fidelity of GelMA, as well as the structural stability and compressive modulus (approximately six times higher) after three weeks of culturing. Therefore, we anticipate that the application of calcium phosphate phase transition to hydrogels may have the potential for hard tissue regeneration.

Polymer Hydrogels and Frontal Polymerization: A Winning Coupling.

Polymer hydrogels are 3D networks consisting of hydrophilic crosslinked macromolecular chains, allowing them to swell and retain water. Since their invention in the 1960s, they have become an outstanding pillar in the design, development, and application of engineered polymer systems suitable for biomedical and pharmaceutical applications (such as drug or cell delivery, the regeneration of hard and soft tissues, wound healing, and bleeding prevention, among others). Despite several well-established synthetic routes for developing polymer hydrogels based on batch polymerization techniques, about fifteen years ago, researchers started to look for alternative methods involving simpler reaction paths, shorter reaction times, and lower energy consumption. In this context, frontal polymerization (FP) has undoubtedly become an alternative and efficient reaction model that allows for the conversion of monomers into polymers via a localized and propagating reaction-by means of exploiting the formation and propagation of a "hot" polymerization front-able to self-sustain and propagate throughout the monomeric mixture. Therefore, the present work aims to summarize the main research outcomes achieved during the last few years concerning the design, preparation, and application of FP-derived polymeric hydrogels, demonstrating the feasibility of this technique for the obtainment of functional 3D networks and providing the reader with some perspectives for the forthcoming years.

Orthodontic tooth extrusion to regenerate missing papilla adjacent to maxillary anterior single implants: A 2- to 7-year retrospective study.

Regeneration of the missing papilla adjacent to single implants in the esthetic zone has always been challenging, despite advances in vertical hard and soft tissue regeneration. Orthodontic tooth extrusion has been shown to effectively gain alveolar bone and gingival tissue. This retrospective study evaluated the effectiveness of orthodontic tooth extrusion on regenerating missing papilla between existing maxillary anterior single implant and its adjacent tooth. Patients who underwent orthodontic tooth extrusion to regenerate missing papilla adjacent to a single implant in the esthetic zone were included in this study. The gingival phenotype, orthodontic extrusion movement, proximal bone level, dento-implant papilla level, facial gingival level, mucogingival junction level, and keratinized tissue width, of the extruded tooth were recorded at pre-orthodontic extrusion (T0 ), post-orthodontic extrusion and retention (T1 ), and latest follow-up (T2 ). A total of 17 maxillary single tooth had orthodontic tooth extrusion to regenerate missing papilla adjacent to 14 maxillary anterior single implants in 14 patients. After a mean follow-up time of 48.4 months, implant success rate was 100% (14/14), with none of the orthodontically extruded teeth being extracted. After a mean extrusion and retention period of 14.3 months, a mean orthodontic extrusion movement of 4.62 ± 0.78 mm was noted with a mean proximal bone level gain of 3.54 ± 0.61 mm (77.0% efficacy), dento-implant papilla level gain of 3.98 ± 0.81 mm (86.8% efficacy), and facial gingival tissue gain of 4.27 mm ± 0.55 mm (93.4% efficacy). A mean keratinized tissue width gain of 4.17 ± 0.49 mm with minimal mean mucogingival junction level change of 0.10 ± 0.30 mm were observed. The efficacy of orthodontic eruption movement on dento-implant papilla gain was less in the thin (80.5%) phenotype group when compared with that in the thick (91.5%) phenotype group. Within the confines of this study, orthodontic extrusion is an effective, noninvasive method in regenerating mid-term stable proximal bone and papilla adjacent to maxillary anterior single implants. This retrospective study presents a mid-term result on orthodontic extrusion as a mean to regenerate dento-implant papilla defect. The extended retention period following orthodontic extrusion showed stable and efficacious proximal bone and papilla gain.

The Effects of Platelet-Rich Fibrin in the Behavior of Mineralizing Cells Related to Bone Tissue Regeneration-A Scoping Review of In Vitro Evidence.

Platelet-rich fibrin (PRF) is a second-generation blood concentrate that serves as an autologous approach for both soft and hard tissue regeneration. It provides a scaffold for cell interaction and promotes the local release of growth factors. PRF has been investigated as an alternative to bone tissue therapy, with the potential to expedite wound healing and bone regeneration, though the mechanisms involved are not yet fully understood. This review aims to explore the in vitro evidence of PRF's effects on the behavior of mineralizing cells related to bone tissue regeneration. A systematic electronic search was conducted up to August 2023, utilizing three databases: PubMed, Web of Science, and Scopus. A total of 76 studies were selected, which presented in vitro evidence of PRF's usefulness, either alone or in conjunction with other biomaterials, for bone tissue treatment. PRF membranes' influence on the proliferation, differentiation, and mineralization of bone cells is linked to the constant release of growth factors, resulting in changes in crucial markers of bone cell metabolism and behavior. This further reinforces their therapeutic potential in wound healing and bone regeneration. While there are some notable differences among the studies, the overall results suggest a positive effect of PRF on cell proliferation, differentiation, mineralization, and a reduction in inflammation. This points to its therapeutic potential in the field of regenerative medicine. Collectively, these findings may help enhance our understanding of how PRF impacts basic physiological processes in bone and mineralized tissue.

Sol-Gel Technologies to Obtain Advanced Bioceramics for Dental Therapeutics.

The aim of this work is to review the application of bioceramic materials in the context of current regenerative dentistry therapies, focusing on the latest advances in the synthesis of advanced materials using the sol-gel methodology. Chemical synthesis, processing and therapeutic possibilities are discussed in a structured way, according to the three main types of ceramic materials used in regenerative dentistry: bioactive glasses and glass ceramics, calcium phosphates and calcium silicates. The morphology and chemical composition of these bioceramics play a crucial role in their biological properties and effectiveness in dental therapeutics. The goal is to understand their chemical, surface, mechanical and biological properties better and develop strategies to control their pore structure, shape, size and compositions. Over the past decades, bioceramic materials have provided excellent results in a wide variety of clinical applications related to hard tissue repair and regeneration. Characteristics, such as their similarity to the chemical composition of the mineral phase of bones and teeth, as well as the possibilities offered by the advances in nanotechnology, are driving the development of new biomimetic materials that are required in regenerative dentistry. The sol-gel technique is a method for producing synthetic bioceramics with high purity and homogeneity at the molecular scale and to control the surfaces, interfaces and porosity at the nanometric scale. The intrinsic nanoporosity of materials produced by the sol-gel technique correlates with the high specific surface area, reactivity and bioactivity of advanced bioceramics.

Do autologous platelet concentrates (APCs) have a role in intra-oral bone regeneration? A critical review of clinical guidelines on decision-making process.

In the past decades, personalized regenerative medicine has gained increased attention. Autologous platelet concentrates (APCs) such as PRP, PRGF, and L-PRF, all serving as a source of a large variety of cells and growth factors that participate in hard and soft tissue healing and regeneration, could play a significant role in regenerative periodontal procedures. This narrative review evaluated the relative impact of APCs in alveolar ridge preservation, sinus floor augmentation, and the regeneration of bony craters around teeth, both as a single substitute or in combination with a xenograft. L-PRF has a significant beneficial effect on alveolar ridge preservation (<alveolar bone resorption, >bone quality). The data for PRGF are less convincing, and PRP is controversial. L-PRF can successfully be used as a single substitute during transcrestal (≥3.5 mm bone gain) as well as 1-stage lateral window sinus floor elevation (>5 mm bone gain). For PRGF and especially PRP the data are very scarce. In the treatment of bony craters around teeth, during open flap debridement, L-PRF as a single substitute showed significant adjunctive benefits (e.g., >PPD reduction, >CAL gain, >crater depth reduction). The data for PRP and PRGF were non-conclusive. Adding PRP or L-PRF to a xenograft during OFD resulted in additional improvements (>PPD reduction, >CAL gain, >bone fill), for PRGF no data were found. Autologous platelet concentrates demonstrated to enhance bone and soft tissue healing in periodontal regenerative procedures. The data for L-PRF were most convincing. L-PRF also has the advantage of a greater simplicity of production, and its 100% autologous character.

Polylactide Degradation Activates Immune Cells by Metabolic Reprogramming.

Polylactide (PLA) is the most widely utilized biopolymer in medicine. However, chronic inflammation and excessive fibrosis resulting from its degradation remain significant obstacles to extended clinical use. Immune cell activation has been correlated to the acidity of breakdown products, yet methods to neutralize the pH have not significantly reduced adverse responses. Using a bioenergetic model, delayed cellular changes were observed that are not apparent in the short-term. Amorphous and semi-crystalline PLA degradation products, including monomeric l-lactic acid, mechanistically remodel metabolism in cells leading to a reactive immune microenvironment characterized by elevated proinflammatory cytokines. Selective inhibition of metabolic reprogramming and altered bioenergetics both reduce these undesirable high cytokine levels and stimulate anti-inflammatory signals. The results present a new biocompatibility paradigm by identifying metabolism as a target for immunomodulation to increase tolerance to biomaterials, ensuring safe clinical application of PLA-based implants for soft- and hard-tissue regeneration, and advancing nanomedicine and drug delivery.

Unravelling the nature-inspired silk sericin - Calcium phosphate hybrid nanocomposites: A promising sustainable biomaterial for hard tissue regeneration applications

Calcium phosphates (CPs) are widely utilized as biomaterials for bone tissue repair due to their osteoinductive and osteoconductive properties. Hydroxyapatite (Ca10 [PO4]6OH2, HAp) and Monetite (CaPHO4, DCPA) are the two different phases of calcium phosphate that have triggered the interest of researchers due to their exceptional properties like bioactivity, biocompatibility, high crystallinity, good mechanical as well as biological characteristics. Current investigations focus on combining CPs with natural proteins to offer innovative biomaterials that accommodate various functional requirements. In the current study, we explore the biomedical relevance of the association of CPs with natural protein silk sericin (SS) composite with calcium phosphate (SCP) at room and low temperatures. The effect of silk sericin concentration and mineralization time on the formation of apatite nanocrystals, including their biocompatibility, were investigated for hard tissue regeneration. The fabricated CP and SCP nanocomposites at room and low temperature were subjected to an X-Ray diffraction technique, revealing a dual phase of calcium phosphate - hydroxyapatite and monetite with hexagonal and triclinic crystal system. Further, the presence of SS and SCP had been confirmed with Fourier-transformed infrared spectroscopy (FTIR) that showed the characteristic bands of amide I at 1642 cm−1 and the dominant phosphate group stretching at 1017 cm−1. Further, nanostructures with rods and tiny blossoms of flower-like enhanced morphologies have been observed for SCP at room and low temperatures. Moreover, the bioactivity of SCPs at low and room temperature materials exhibited apatite layer formation from day 7 of immersion which was confirmed with structural and morphological analysis. The cell viability assay demonstrated that the SCP nanocomposites have over 130% of viable cells. Therefore, fabricated SCP nanostructures are proven to be highly biocompatible with a rapid rate of mineralization capability, which will be a promising candidate for hard tissue applications.

Promoting vascularized bone regeneration via strontium-incorporated hydroxyapatite bioceramic

Angiogenesis, well-coupled with osteogenesis, plays an indispensable and vital role in modulating hard tissue regeneration. Thus, simultaneously promoting osteogenesis and angiogenesis in bone reconstruction process is important. Essential trace elements have shown great potential in enhancing osteogenesis and angiogenesis, providing an effective strategy to design grafts for vascularized bone regeneration. In this study, four types of bioactive bioceramic, including hydroxyapatite (HA), strontium (Sr)-incorporated hydroxyapatite (Sr5-HA, Sr10-HA, Sr20-HA) with Sr ions concentrations of 0, 5, 10 and 20%, were investigated for their osteogenic and angiogenic properties. The in vitro results showed that Sr-HA could enhance the proliferation and osteogenic differentiation of BMSCs via Erk1/2 MAPK and PI3K/AKT signaling pathways, and promote the proliferation and angiogenic gene expression of HUVECs via PI3K/AKT pathways. Moreover, HUVECs conditioned medium could apparently promote the osteogenesis of BMSCs, and BMSCs conditioned medium could enhance the angiogenic capacity of HUVECs. Furthermore, in vivo angiogenesis evaluation and bone formation estimation indicated that enhanced newly-formed vessels and new bone formation were observed in Sr-HA porous scaffolds compared to pure HA scaffold. Thus, this study suggests that Sr-incorporation is a promising modification strategy for bone implants to achieve enhanced angiogenic and osteogenic capacities.

Twenty-five years of recombinant human growth factors rhPDGF-BB and rhBMP-2 in oral hard and soft tissue regeneration.

Contemporary oral tissue engineering strategies involve recombinant human growth factor approaches to stimulate diverse cellular processes including cell differentiation, migration, recruitment, and proliferation at grafted areas. Recombinant human growth factor applications in oral hard and soft tissue regeneration have been progressively researched over the last 25 years. Growth factor-mediated surgical approaches aim to accelerate healing, tissue reconstruction, and patient recovery. Thus, regenerative approaches involving growth factors such as recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human bone morphogenetic proteins (rhBMPs) have shown certain advantages over invasive traditional surgical approaches in severe hard and soft tissue defects. Several clinical studies assessed the outcomes of rhBMP-2 in diverse clinical applications for implant site development and bone augmentation. Current evidence regarding the clinical benefits of rhBMP-2 compared to conventional therapies is inconclusive. Nevertheless, it seems that rhBMP-2 can promote faster wound healing processes and enhance de novo bone formation, which may be particularly favorable in patients with compromised bone healing capacity or limited donor sites. rhPDGF-BB has been extensively applied for periodontal regenerative procedures and for the treatment of gingival recessions, showing consistent and positive outcomes. Nevertheless, current evidence regarding its benefits at implant and edentulous sites is limited. The present review explores and depicts the current applications, outcomes, and evidence-based clinical recommendations of rhPDGF-BB and rhBMPs for oral tissue regeneration.

3D interconnected porous PMMA scaffold integrating with advanced nanostructured CaP-based biomaterials for rapid bone repair and regeneration

Bioactive scaffolds with polymer and nanostructured bioactive glass-based composites are promising materials for regenerative applications in consequence of close mimics of natural bone composition. Poly methyl methacrylate (PMMA) is a highly preferred thermoplastic polymer for orthopedic applications as it has good biocompatibility. Different kinds of bioactive, biodegradable as well as biocompatible biomaterial composites such as Bioglass (BG), Hydroxyapatite (Hap), and Tricalcium phosphate (TCP) can be integrated with PMMA, so as to augment the bioactivity, porosity as well as regeneration of hard tissues in human body. Among the bioactive glass, 60S BG (Bioactive glass with 60 percentage of Silica without Sodium ions) is better materials among aforementioned systems owning to mechanical stability as well as controlled bioactive material. In this work, the fabrication of PMMA-CaP (calcium phosphate)-based scaffolds were carried out by Thermal Induced Phase Separation method (TIPS). X-ray diffractogram analysis (XRD) is used to examine the physiochemical properties of the scaffolds that evidently reveal the presence of calcium phosphate besides calcium phosphate silicate phases. The Field Emission Scanning Electron Microscopy (FESEM) studies obviously exhibited the microstructure of the scaffolds as well as their interconnected porous morphology. The PMMA/60S BG/TCP (C50) scaffold has the maximum pore size, measuring 77 ± 23 μm, while the average pore size ranges from 50 ± 20 to 80 ± 23 μm. By performing a liquid displacement method, the C50 scaffold is found to have the largest porosity of 50%, high hydrophilicity of 118.16°, and a compression test reveals the scaffolds to have a maximum compressive strength of 0.16 MPa. The emergence of bone-like apatite on the scaffold surface after 1st and 21st days of SBF immersion is further supported by in vitro bioactivity studies. Cytocompatibility and hemocompatibility analyses undoubtedly confirmed the biocompatibility behavior of PMMA-based bioactive scaffolds. Nano-CT investigation demonstrates that PMMA-CaP scaffolds provide more or less alike morphologies of composites that resemble the natural bone. Therefore, this combination of scaffolds could be considered as potential biomaterials for bone regeneration application. This detailed study promisingly demonstrates the eminence of the unique scaffolds in the direction of regenerative medicines.