Effect of the Addition of Inorganic Fillers on the Properties of Degradable Polymeric Blends for Bone Tissue Engineering.

Bone tissue exhibits self-healing properties; however, not all defects can be repaired without surgical intervention. Bone tissue engineering offers artificial scaffolds, which can act as a temporary matrix for bone regeneration. The aim of this study was to manufacture scaffolds made of poly(lactic acid), poly(ε-caprolactone), poly(propylene fumarate), and poly(ethylene glycol) modified with bioglass, beta tricalcium phosphate (TCP), and/or wollastonite (W) particles. The scaffolds were fabricated using a gel-casting method and observed with optical and scanning electron microscopes. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), wettability, and degradation tests were conducted. The highest content of TCP without W in the composition caused the highest hydrophilicity (water contact angle of 61.9 ± 6.3°), the fastest degradation rate (7% mass loss within 28 days), moderate ability to precipitate CaP after incubation in PBS, and no cytotoxicity for L929 cells. The highest content of W without TCP caused the highest hydrophobicity (water contact angle of 83.4 ± 1.7°), the lowest thermal stability, slower degradation (3% mass loss within 28 days), and did not evoke CaP precipitation. Moreover, some signs of cytotoxicity on day 1 were observed. The samples with both TCP and W showed moderate properties and the best cytocompatibility on day 4. Interestingly, they were covered with typical cauliflower-like hydroxyapatite deposits after incubation in phosphate-buffered saline (PBS), which might be a sign of their excellent bioactivity.

Preparation of PDA-GO/CS composite scaffold and its effects on the biological properties of human dental pulp stem cells.

Reduced graphene oxide (rGO) is an graphene oxide (GO) derivative of graphene, which has a large specific surface area and exhibited satisfactory physicochemical characteristics. In this experiment, GO was reduced by PDA to generate PDA-GO complex, and then PDA-GO was combined with Chitosan (CS) to synthesize PDA-GO/CS composite scaffold. PDA-GO was added to CS to improve the degradation rate of CS, and it was hoped that PDA-GO/CS composite scaffolds could be used in bone tissue engineering. Physicochemical and antimicrobial properties of the different composite scaffolds were examined to find the optimal mass fraction. Besides, we examined the scaffold's biocompatibility by Phalloidin staining and Live and Dead fluorescent staining.Finally, we applied ALP staining, RT-qPCR, and Alizarin red S staining to detect the effect of PDA-GO/CS on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). The results showed that PDA-GO composite was successfully prepared and PDA-GO/CS composite scaffold was synthesized by combining PDA-GO with CS. Among them, 0.3%PDA-GO/CS scaffolds improves the antibacterial activity and hydrophilicity of CS, while reducing the degradation rate. In vitro, PDA-GO/CS has superior biocompatibility and enhances the early proliferation, migration and osteogenic differentiation of hDPSCs. In conclusion, PDA-GO/CS is a new scaffold materialsuitable for cell culture and has promising application prospect as scaffold for bone tissue engineering.

A hydrogel-fiber-hydrogel composite scaffold based on silk fibroin with the dual-delivery of oxygen and quercetin.

Supplying sufficient oxygen within the scaffolds is one of the essential hindrances in tissue engineering that can be resolved by oxygen-generating biomaterials (OGBs). Two main issues related to OGBs are controlling oxygenation and reactive oxygen species (ROS). To address these concerns, we developed a composite scaffold entailing three layers (hydrogel-electrospun fibers-hydrogel) with antioxidant and antibacterial properties. The fibers, the middle layer, reinforced the composite structure, enhancing the mechanical strength from 4.27 ± 0.15 to 8.27 ± 0.25 kPa; also, this layer is made of calcium peroxide and silk fibroin (SF) through electrospinning, which enables oxygen delivery. The first and third layers are physical SF hydrogels to control oxygen release, containing quercetin (Q), a nonenzymatic antioxidant. This composite scaffold resulted in almost more than 40 mmHg of oxygen release for at least 13 days, and compared with similar studies is in a high range. Here, Q was used for the first time for an OGB to scavenge the possible ROS. Q delivery not only led to antioxidant activity but also stabilized oxygen release and enhanced cell viability. Based on the given results, this composite scaffold can be introduced as a safe and controllable oxygen supplier, which is promising for tissue engineering applications, particularly for bone.

Two-dimensional nanovermiculite and polycaprolactone electrospun fibers composite scaffolds promoting diabetic wound healing.

BACKGROUND: Promoting diabetic wound healing is still a challenge, and angiogenesis is believed to be essential for diabetic wound healing. Vermiculite is a natural clay material that is very easy to obtain and exhibits excellent properties of releasing bioactive ions, buffering pH, adsorption, and heat insulation. However, there are still many unsolved difficulties in obtaining two-dimensional vermiculite and using it in the biomedical field in a suitable form. RESULTS: In this study, we present a versatile organic-inorganic composite scaffold, which was constructed by embedding two-dimensional vermiculite nanosheets in polycaprolactone electrospun fibers, for enhancing angiogenesis through activation of the HIF-1α signaling pathway and promoting diabetic wound healing both in vitro and in vivo. CONCLUSIONS: Together, the rational-designed polycaprolactone electrospun fibers-based composite scaffolds integrated with two-dimensional vermiculite nanosheets could significantly improve neo-vascularization, re-epithelialization, and collagen formation in the diabetic wound bed, thus promoting diabetic wound healing. This study provides a new strategy for constructing bioactive materials for highly efficient diabetic wound healing.

Development of Biocomposite Alginate-Cuttlebone-Gelatin 3D Printing Inks Designed for Scaffolds with Bone Regeneration Potential.

Fabrication of three-dimensional (3D) scaffolds using natural biomaterials introduces valuable opportunities in bone tissue reconstruction and regeneration. The current study aimed at the development of paste-like 3D printing inks with an extracellular matrix-inspired formulation based on marine materials: sodium alginate (SA), cuttlebone (CB), and fish gelatin (FG). Macroporous scaffolds with microporous biocomposite filaments were obtained by 3D printing combined with post-printing crosslinking. CB fragments were used for their potential to stimulate biomineralization. Alginate enhanced CB embedding within the polymer matrix as confirmed by scanning electron microscopy (ESEM) and micro-computer tomography (micro-CT) and improved the deformation under controlled compression as revealed by micro-CT. SA addition resulted in a modulation of the bulk and surface mechanical behavior, and lead to more elongated cell morphology as imaged by confocal microscopy and ESEM after the adhesion of MC3T3-E1 preosteoblasts at 48 h. Formation of a new mineral phase was detected on the scaffold's surface after cell cultures. All the results were correlated with the scaffolds' compositions. Overall, the study reveals the potential of the marine materials-containing inks to deliver 3D scaffolds with potential for bone regeneration applications.

Hybrid Core-Shell Polymer Scaffold for Bone Tissue Regeneration.

A great promise for tissue engineering is represented by scaffolds that host stem cells during proliferation and differentiation and simultaneously replace damaged tissue while maintaining the main vital functions. In this paper, a novel process was adopted to develop composite scaffolds with a core-shell structure for bone tissue regeneration, in which the core has the main function of temporary mechanical support, and the shell enhances biocompatibility and provides bioactive properties. An interconnected porous core was safely obtained, avoiding solvents or other chemical issues, by blending poly(lactic acid), poly(ε-caprolactone) and leachable superabsorbent polymer particles. After particle leaching in water, the core was grafted with a gelatin/chitosan hydrogel shell to create a cell-friendly bioactive environment within its pores. The physicochemical, morphological, and mechanical characterization of the hybrid structure and of its component materials was carried out by means of infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and mechanical testing under different loading conditions. These hybrid polymer devices were found to closely mimic both the morphology and the stiffness of bones. In addition, in vitro studies showed that the core-shell scaffolds are efficiently seeded by human mesenchymal stromal cells, which remain viable, proliferate, and are capable of differentiating towards the osteogenic phenotype if adequately stimulated.

Comparison of Hydroxyapatite/Poly(lactide-co-glycolide) and Hydroxyapatite/Polyethyleneimine Composite Scaffolds in Bone Regeneration of Swine Mandibular Critical Size Defects: In Vivo Study.

Reconstruction of jaw bone defects present a significant problem because of specific aesthetic and functional requirements. Although widely used, the transplantation of standard autograft and allograft materials is still associated with significant constraints. Composite scaffolds, combining advantages of biodegradable polymers with bioceramics, have potential to overcome limitations of standard grafts. Polyethyleneimine could be an interesting novel biocompatible polymer for scaffold construction due to its biocompatibility and chemical structure. To date, there have been no in vivo studies assessing biological properties of hydroxyapatite bioceramics scaffold modified with polyethyleneimine. The aim of this study was to evaluate in vivo effects of composite scaffolds of hydroxyapatite ceramics and poly(lactide-co-glycolide) and novel polyethyleneimine on bone repair in swine's mandibular defects, and to compare them to conventional bone allograft (BioOss). Scaffolds were prepared using the method of polymer foam template in three steps. Pigs, 3 months old, were used and defects were made in the canine, premolar, and molar area of their mandibles. Four months following the surgical procedure, the bone was analyzed using radiological, histological, and gene expression techniques. Hydroxyapatite ceramics/polyethyleneimine composite scaffold demonstrated improved biological behavior compared to conventional allograft in treatment of swine's mandibular defects, in terms of bone density and bone tissue histological characteristics.

Nanomaterials and their composite scaffolds for photothermal therapy and tissue engineering applications.

Photothermal therapy (PTT) has attracted broad attention as a promising method for cancer therapy with less severe side effects than conventional radiation therapy, chemotherapy and surgical resection. PTT relies on the photoconversion capacity of photothermal agents (PTAs), and a wide variety of nanomaterials have been employed as PTAs for cancer therapy due to their excellent photothermal properties. The PTAs are systematically or locally administered and become enriched in cancer cells to increase ablation efficiency. In recent years, PTAs and three-dimensional scaffolds have been hybridized to realize the local delivery of PTAs for the repeated ablation of cancer cells. Meanwhile, the composite scaffolds can stimulate the reconstruction and regeneration of the functional tissues and organs after ablation of cancer cells. A variety of composite scaffolds of photothermal nanomaterials have been prepared to combine the advantages of different modalities to maximize their therapeutic efficacy with minimal side effects. The synergistic effects make the composite scaffolds attractive for biomedical applications. This review summarizes these latest advances and discusses the future prospects.

Fabrication and Evaluation of Alginate/Bacterial Cellulose Nanocrystals-Chitosan-Gelatin Composite Scaffolds.

It is common knowledge that pure alginate hydrogel is more likely to have weak mechanical strength, a lack of cell recognition sites, extensive swelling and uncontrolled degradation, and thus be unable to satisfy the demands of the ideal scaffold. To address these problems, we attempted to fabricate alginate/bacterial cellulose nanocrystals-chitosan-gelatin (Alg/BCNs-CS-GT) composite scaffolds using the combined method involving the incorporation of BCNs in the alginate matrix, internal gelation through the hydroxyapatite-d-glucono-δ-lactone (HAP-GDL) complex, and layer-by-layer (LBL) electrostatic assembly of polyelectrolytes. Meanwhile, the effect of various contents of BCNs on the scaffold morphology, porosity, mechanical properties, and swelling and degradation behavior was investigated. The experimental results showed that the fabricated Alg/BCNs-CS-GT composite scaffolds exhibited regular 3D morphologies and well-developed pore structures. With the increase in BCNs content, the pore size of Alg/BCNs-CS-GT composite scaffolds was gradually reduced from 200 µm to 70 µm. Furthermore, BCNs were fully embedded in the alginate matrix through the intermolecular hydrogen bond with alginate. Moreover, the addition of BCNs could effectively control the swelling and biodegradation of the Alg/BCNs-CS-GT composite scaffolds. Furthermore, the in vitro cytotoxicity studies indicated that the porous fiber network of BCNs could fully mimic the extracellular matrix structure, which promoted the adhesion and spreading of MG63 cells and MC3T3-E1 cells on the Alg/BCNs-CS-GT composite scaffolds. In addition, these cells could grow in the 3D-porous structure of composite scaffolds, which exhibited good proliferative viability. Based on the effect of BCNs on the cytocompatibility of composite scaffolds, the optimum BCNs content for the Alg/BCNs-CS-GT composite scaffolds was 0.2% (w/v). On the basis of good merits, such as regular 3D morphology, well-developed pore structure, controlled swelling and biodegradation behavior, and good cytocompatibility, the Alg/BCNs-CS-GT composite scaffolds may exhibit great potential as the ideal scaffold in the bone tissue engineering field.

Magnetic Composite Scaffolds for Potential Applications in Radiochemotherapy of Malignant Bone Tumors.

Background and objectives: Cancer is the second leading cause of death globally, an alarming but expected increase. In comparison to other types of cancer, malignant bone tumors are unusual and their treatment is a real challenge. This paper's main purpose is the study of the potential application of composite scaffolds based on biopolymers and calcium phosphates with the inclusion of magnetic nanoparticles in combination therapy for malignant bone tumors. Materials and Methods: The first step was to investigate if X-rays could modify the scaffolds' properties. In vitro degradation of the scaffolds exposed to X-rays was analyzed, as well as their interaction with phosphate buffer solutions and cells. The second step was to load an anti-tumoral drug (doxorubicin) and to study in vitro drug release and its interaction with cells. The chemical structure of the scaffolds and their morphology were studied. Results: Analyses showed that X-ray irradiation did not influence the scaffolds' features. Doxorubicin release was gradual and its interaction with cells showed cytotoxic effects on cells after 72 h of direct contact. Conclusions: The obtained scaffolds could be considered in further studies regarding combination therapy for malignant bone tumors.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering.

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.

Fabrication and characterization of nanohydroxyapatite/chitosan/decellularized placenta scaffold for bone tissue engineering applications.

Novel biomaterials are necessary to fabricate biomimetic scaffolds for bone tissue engineering. In the present experiment, we aimed to fabricate and evaluate the osteogenic properties of nanohydroxyapatite/chitosan/decellularized placenta (nHA.Cs.dPL) composite scaffolds. The human placenta was decellularized (dPL), characterized, and digested in pepsin to form the hydrogel. nHA.Cs.dPL scaffolds were fabricated using salt leaching/freeze drying and evaluated for their morphology, chemical composition, swelling, porosity, degradation, mechanical strength, and biocompatibility. Saos-2 cells were seeded on scaffolds, and their osteogenic properties were investigated by evaluating alkaline phosphatase (ALP), osteocalcin (OCN), collagen type 1 (COL I) expression, and calcium deposition under osteogenic differentiation. The dPL was prepared with minimized DNA content and a well-preserved porous structure. Scaffolds were highly porous with interconnected pores and exhibited appropriate swelling and degradation rates supporting saos-2 cell attachment and proliferation. dPL improved scaffold physicochemical features and increased cell proliferation, ALP, OCN, COL I expression, and calcium deposition under osteogenic differentiation induction. nHA.Cs.dPL composite scaffolds provide a 3D microenvironment with superior physicochemical features that support saos-2 cell adhesion, proliferation, and osteogenic differentiation.

A 3D-Printed Scaffold for Repairing Bone Defects.

The treatment of bone defects has always posed challenges in the field of orthopedics. Scaffolds, as a vital component of bone tissue engineering, offer significant advantages in the research and treatment of clinical bone defects. This study aims to provide an overview of how 3D printing technology is applied in the production of bone repair scaffolds. Depending on the materials used, the 3D-printed scaffolds can be classified into two types: single-component scaffolds and composite scaffolds. We have conducted a comprehensive analysis of material composition, the characteristics of 3D printing, performance, advantages, disadvantages, and applications for each scaffold type. Furthermore, based on the current research status and progress, we offer suggestions for future research in this area. In conclusion, this review acts as a valuable reference for advancing the research in the field of bone repair scaffolds.

A Superparamagnetic Composite Hydrogel Scaffold as In Vivo Dynamic Monitorable Theranostic Platform for Osteoarthritis Regeneration.

Osteoarthritis (OA) is a prevalent disease, characterized by subchondral fractures in its initial stages, which has no precise and specific treatment now. Here, a novel multifunctional scaffold is synthesized by photopolymerizing glycidyl methacrylate-modified hyaluronic acid (GMHA) as the matrix in the presence of hollow porous magnetic microspheres based on hydroxyapatite. In vivo subchondral bone repairing results demonstrate that the scaffold's meticulous design has most suitable properties for subchondral bone repair. The porous structure of inorganic particles within the scaffold facilitates efficient transport of loaded exogenous vascular endothelial growth factor (VEGF). The Fe3O4 nanoparticles assembled in microspheres promote the osteogenic differentiation of bone marrow mesenchymal stem cells and accelerate the new bone generation. These features enable the scaffold to exhibit favorable subchondral bone repair properties and attain high cartilage repair scores. The therapy results prove that the subchondral bone support considerably influences the upper cartilage repair process. Furthermore, magnetic resonance imaging monitoring demonstrates that Fe3O4 nanoparticles, which are gradually replaced by new bone during osteochondral defect repair, allow a noninvasive and radiation-free assessment to track the newborn bone during the OA repair process. The composite hydrogel scaffold (CHS) provides a versatile platform for biomedical applications in OA treatment.

Three-dimensional porous polycaprolactone/chitosan/bioactive glass scaffold for bone tissue engineering.

Three-dimensional (3D) porous scaffolds based on polycaprolactone (PCL)/chitosan (CS)/bioactive glass (BG) nanoparticle composites were fabricated by the freeze-drying technique for bone tissue engineering. The physiochemical properties of the developed PCL/CS/BG scaffolds were studied using FTIR, XRD, EDX and SEM. Furthermore, the swelling degree, porosity, water retention ability, compression strength, in vitro biodegradation, bioactivity and biocompatibility of the scaffolds were examined. The PCL/CS/BG scaffolds with 4 wt. % of BG content presented adequate pore size (106 µm), porosity (156%), water swelling degree (128%), water retention ability (179%), compressive strength (3.7 MPa) and controlled degradation behavior, which could be ideal for bone tissue engineering. The PCL/CS/BG composite scaffolds showed good antimicrobial activity against both test bacteria and fungi. The MTT assay demonstrated the biocompatibility of PCL/CS/BG scaffolds against C3H10T1/2 cell line. The Alizarin red staining assay confirmed the osteogenic activity of the PCL/CS/BG scaffolds.

Methacrylated Carboxymethyl Chitosan Scaffold Containing Icariin-Loaded Short Fibers for Antibacterial, Hemostasis, and Bone Regeneration.

Bone defects typically result in bone nonunion, delayed or nonhealing, and localized dysfunction, and commonly used clinical treatments (i.e., autologous and allogeneic grafts) have limited results. The multifunctional bone tissue engineering scaffold provides a new treatment for the repair of bone defects. Herein, a three-dimensional porous composite scaffold with stable mechanical support, effective antibacterial and hemostasis properties, and the ability to promote the rapid repair of bone defects was synthesized using methacrylated carboxymethyl chitosan and icariin-loaded poly-l-lactide/gelatin short fibers (M-CMCS-SFs). Icariin-loaded SFs in the M-CMCS scaffold resulted in the sustained release of osteogenic agents, which was beneficial for mechanical reinforcement. Both the porous structure and the use of chitosan facilitate the effective absorption of blood and fluid exudates. Moreover, its superior antibacterial properties could prevent the occurrence of inflammation and infection. When cultured with bone mesenchymal stem cells, the composite scaffold showed a promotion in osteogenic differentiation. Taken together, such a multifunctional composite scaffold showed comprehensive performance in antibacterial, hemostasis, and bone regeneration, thus holding promising potential in the repair of bone defects and related medical treatments.

Microstructural, Fluid Dynamic, and Mechanical Characterization of Zinc Oxide and Magnesium Chloride-Modified Hydrogel Scaffolds.

Scaffolds for the filling and regeneration of osteochondral defects are a current challenge in the biomaterials field, and solutions with greater functionality are still being sought. The novel approach of this work was to obtain scaffolds with biologically active additives possessing microstructural, permeability, and mechanical properties, mimicking the complexity of natural cartilage. Four types of scaffolds with a gelatin/alginate matrix modified with hydroxyapatite were obtained, and the relationship between the modifiers and substrate properties was evaluated. They differed in the type of second modifier used, which was hydrated MgCl2 in two proportions, ZnO, and nanohydroxyapatite. The samples were obtained by freeze-drying by using two-stage freezing. Based on microstructural observations combined with X-ray microanalysis, the microstructure of the samples and the elemental content were assessed. Permeability and mechanical tests were also performed. The scaffolds exhibited a network of interconnected pores and complex microarchitecture, with lower porosity at the surface (15 ± 7 to 29 ± 6%) and higher porosity at the center (67 ± 8 to 75 ± 8%). The additives had varying effects on the pore sizes and permeabilities of the samples. ZnO yielded the most permeable scaffolds (5.92 × 10-11 m2), whereas nanohydroxyapatite yielded the scaffold with the lowest permeability (1.18 × 10-11 m2), values within the range reported for trabecular bone. The magnesium content had no statistically significant effect on the permeability. The best mechanical parameters were obtained for ZnO samples and those containing hydrated MgCl2. The scaffold's properties meet the criteria for filling osteochondral defects. The developed scaffolds follow a biomimetic approach in terms of hierarchical microarchitecture and mechanical parameters as well as chemical composition. The obtained composite materials have the potential as biomimetic scaffolds for the regeneration of osteochondral defects.

Lactobacillus reuteri biofilms formed on porous zein/cellulose scaffolds: Synbiotics to regulate intestinal microbiota.

Supplementing probiotics or indigestible carbohydrates is a usual strategy to prevent or revert unhealthy states of the gut by reshaping gut microbiota. One criterion that probiotics are efficacious is the capacity to survive in the gastrointestinal tract. Biofilm is the common growth mode of microorganisms with high tolerances toward harsh environments. Suitable scaffolds are crucial for successful biofilm culture and large-scale production of biofilm-phenotype probiotics. However, the role of scaffolds containing indigestible carbohydrates in biofilm formation has not been studied. In this study, porous zein/cellulose composite scaffolds provided nitrogen sources and carbon sources simultaneously at the solid/liquid interfaces, being beneficial to the biofilm formation of Lactobacillus reuteri. The biofilms showed 2.1-17.4 times higher tolerances in different gastrointestinal conditions. In human fecal fermentation, the biofilms combined with the zein/cellulose composite scaffolds act as the "synbiotics" positively modulating the gut microbiota and the short-chain fatty acids (SCFAs), where biofilms provide probiotics and scaffolds provide prebiotics. The "synbiotics" show a more positive regulation ability than planktonic L. reuteri, presenting potential applications in gut health interventions. These results provide an understanding of the synergistic effects of biofilm-phenotype probiotics and indigestible carbohydrates contained in the "synbiotics" in gut microbiota modulation.

Composite Zonal Scaffolds of Collagen I/II for Meniscus Regeneration.

The meniscus is divided into three zones according to its vascularity: an external vascularized red-red zone mainly comprising collagen I, a red-white interphase zone mainly comprising collagens I and II, and an internal white-white zone rich in collagen II. Known scaffolds used to treat meniscal injuries do not reflect the chemical composition of the vascular areas of the meniscus. Therefore, in this study, four composite zonal scaffolds (named A, B, C, and D) were developed and characterized; the developed scaffolds exhibited the main chemical components of the external (collagen I), interphase (collagens I/II), and internal (collagen II) zones of the meniscus. Noncomposite scaffolds were also produced (named E), which had the same shape as the composite scaffolds but were entirely made of collagen I. The composite zonal scaffolds were prepared using different concentrations of collagen I and the same concentration of collagen II and were either cross-linked with genipin or not cross-linked. Porous, biodegradable, and hydrophilic scaffolds with an expected chemical composition were obtained. Their pore size was smaller than the size reported for the meniscus substitutes; however, all scaffolds allowed the adhesion and proliferation of human adipose-derived stem cells (hADSCs) and were not cytotoxic. Data from enzymatic degradation and hADSC proliferation assays were considered for choosing the cross-linked composite scaffolds along with the collagen I scaffold and to test if composite zonal scaffolds seeded with hADSC and cultured with differentiation medium produced fibrocartilage-like tissue different from that formed in noncomposite scaffolds. After 21 days of culture, hADSCs seeded on composite scaffolds afforded an extracellular matrix with aggrecan, whereas hADSCs seeded on noncomposite collagen I scaffolds formed a matrix-like fibrocartilage without aggrecan.

Clinical translation of polycaprolactone-based tissue engineering scaffolds, fabricated via additive manufacturing: A review of their craniofacial applications.

The craniofacial region is characterized by its intricate bony anatomy and exposure to heightened functional forces presenting a unique challenge for reconstruction. Additive manufacturing has revolutionized the creation of customized scaffolds with interconnected pores and biomimetic microarchitecture, offering precise adaptation to various craniofacial defects. Within this domain, medical-grade poly(ε-caprolactone) (PCL) has been extensively used for the fabrication of 3D printed scaffolds, specifically tailored for bone regeneration. Its adoption for load-bearing applications was driven mainly by its mechanical properties, adjustable biodegradation rates, and high biocompatibility. The present review aims to consolidating current insights into the clinical translation of PCL-based constructs designed for bone regeneration. It encompasses recent advances in enhancing the mechanical properties and augmenting biodegradation rates of PCL and PCL-based composite scaffolds. Moreover, it delves into various strategies improving cell proliferation and the osteogenic potential of PCL-based materials. These strategies provide insight into the refinement of scaffold microarchitecture, composition, and surface treatments or coatings, that include certain bioactive molecules such as growth factors, proteins, and ceramic nanoparticles. The review critically examines published data on the clinical applications of PCL scaffolds in both extraoral and intraoral craniofacial reconstructions. These applications include cranioplasty, nasal and orbital floor reconstruction, maxillofacial reconstruction, and intraoral bone regeneration. Patient demographics, surgical procedures, follow-up periods, complications and failures are thoroughly discussed. Although results from extraoral applications in the craniofacial region are encouraging, intraoral applications present a high frequency of complications and related failures. Moving forward, future studies should prioritize refining the clinical performance, particularly in the domain of intraoral applications, and providing comprehensive data on the long-term outcomes of PCL-based scaffolds in bone regeneration. Future perspective and limitations regarding the transition of such constructs from bench to bedside are also discussed.