Preliminary study on the preparation of antler powder/chitosan/ß-glycerophosphate sodium/polyvinyl alcohol porous hydrogel scaffolds and their osteogenic effects.

Introduction: The production of bone-like structural scaffolds through bone tissue engineering technology is a promising method for bone regeneration to repair bone defects. Deer antler, an easily harvested and abundantly sourced initial bone tissue structure, resembles the composition and structure of human cancellous bone and can serve as a new material for allogeneic bone transplantation. Methods: This study involved the preparation and characterization of antler powder/chitosan/ß-glycerophosphate sodium/polyvinyl alcohol (AP/CS/ß-GP/PVA) porous hydrogel scaffolds to verify their material properties and osteogenic mechanisms. The microstructure, hydrophilicity, and mechanical properties of the scaffolds were studied using Scanning Electron Microscopy (SEM), contact angle measurement, and a universal material testing machine. The interactions between the various components were investigated using Fourier-Transform Infrared Spectroscopy (FTIR). Biocompatibility, osteogenic properties, and expression of osteogenesis-related proteins of the scaffolds were evaluated through Cell Counting Kit-8 (CCK-8) assays, alkaline phosphatase staining, Alizarin Red staining, live/dead cell staining, and Western blot analysis. Results: The results showed that as the content of deer antler powder increased, both the hydrophilicity and mechanical properties of the scaffold materials improved, while the porosity slightly decreased with an increase in deer antler powder content. Cell culture experiments demonstrated that scaffolds with a higher proportion of deer antler powder were beneficial for the proliferation and differentiation of mouse pre-osteoblast (MC3T3-E1) cells, with the scaffolds containing 10% and 8% deer antler powder showing the best effects. The upregulation of RUNX2, OCN, OSX, and OPN protein expression may promote differentiation. Discussion: Therefore, the AP/CS/ß-GP/PVA hydrogel scaffolds have the potential to become a promising biomaterial for bone tissue engineering.

Melt electrowriting of poly(ϵ-caprolactone)-poly(ethylene glycol) backbone polymer blend scaffolds with improved hydrophilicity and functionality.

Melt electrowriting (MEW) is an additive manufacturing technique that harnesses electro-hydrodynamic phenomena to produce 3D-printed fibres with diameters on the scale of 10s of microns. The ability to print at this small scale provides opportunities to create structures with incredibly fine resolution and highly defined morphology. The current gold standard material for MEW is poly(ϵ-caprolactone) (PCL), a polymer with excellent biocompatibility but lacking in chemical groups that can allow intrinsic additional functionality. To provide this functionality while maintaining PCL's positive attributes, blending was performed with a Poly(Ethylene Glycol) (PEG)-based Acrylate endcapped Urethane-based Precursor (AUP). AUPs are a group of polymers, built on a backbone of existing polymers, which introduce additional functionality by the addition of one or more acrylate groups that terminate the polymer chain of a backbone polymer. By blending with a 20kDa AUP-PEG in small amounts, it is shown that MEW attributes are preserved, producing high-quality meshes. Blends were produced in various PCL:AUP weight ratios (100:0, 90:10 and 0:100) and processed into both solvent-cast films and MEW meshes that were used to characterise the properties of the blends. It was found that the addition of AUP-PEG to PCL significantly increases the hydrophilicity of structures produced with these polymers, and adds swelling capability compared to the non-swelling PCL. The developed blend (90:10) is shown to be processable using MEW, and the quality of manufactured scaffolds is evaluated against pure PCL scaffolds by performing scanning electron microscopy image analysis, with the quality of the novel MEW blend scaffolds showing comparable quality to that of pure PCL. The presence of the functionalisable AUP material on the surface of the developed scaffolds is also confirmed using fluorescence labelling of the acrylate groups. Biocompatibility of the MEW-processable blend was confirmed through a cell viability study, which found a high degree of cytocompatibility.

3D printed kombucha biomaterial as a tissue scaffold and L929 cell cytotoxicity assay.

Tissue engineering includes the construction of tissue-organ scaffold. The advantage of three-dimensional scaffolds over two-dimensional scaffolds is that they provide homeostasis for a longer time. The microbial community in Symbiotic culture of bacteria and yeast (SCOBY) can be a source for kombucha (kombu tea) production. In this study, it was aimed to investigate the usage of SCOBY, which produces bacterial cellulose, as a biomaterial and 3D scaffold material. 3D printable biomaterial was obtained by partial hydrolysis of oolong tea and black tea kombucha biofilms. In order to investigate the usage of 3D kombucha biomaterial as a tissue scaffold, "L929 cell line 3D cell culture" was created and cell viability was tested in the biomaterial. At the end of the 21st day, black tea showed 51% and oolong tea 73% viability. The cytotoxicity of the materials prepared by lyophilizing oolong and black tea kombucha beverages in fibroblast cell culture was determined. Black tea IC50 value: 7.53 mg, oolong tea IC50 value is found as 6.05 mg. Fibroblast viability in 3D biomaterial + lyophilized oolong and black tea kombucha beverages, which were created using the amounts determined to these values, were investigated by cell culture Fibroblasts in lyophilized and 3D biomaterial showed viability of 58% in black tea and 78% in oolong tea at the end of the 7th day. In SEM analysis, it was concluded that fibroblast cells created adhesion to the biomaterial. 3D biomaterial from kombucha mushroom culture can be used as tissue scaffold and biomaterial.

3D Poly (L-lactic acid) fibrous sponge with interconnected porous structure for bone tissue scaffold.

Large bone defects, often resulting from trauma and disease, present significant clinical challenges. Electrospun fibrous scaffolds closely resembling the morphology and structure of natural ECM are highly interested in bone tissue engineering. However, the traditional electrospun fibrous scaffold has some limitations, including lacking interconnected macropores and behaving as a 2D scaffold. To address these challenges, a sponge-like electrospun poly(L-lactic acid) (PLLA)/polycaprolactone (PCL) fibrous scaffold has been developed by an innovative and convenient method (i.e., electrospinning, homogenization, progen leaching and shaping). The resulting scaffold exhibited a highly porous structure (overall porosity = 85.9 %) with interconnected, regular macropores, mimicking the natural extracellular matrix. Moreover, the incorporation of bioactive glass (BG) particles improved the hydrophilicity (water contact angle = 79.7°) and biocompatibility and promoted osteoblast cell growth. In-vitro 10-day experiment revealed that the scaffolds led to high cell viability. The increment of the proliferation rates was 195.4 % at day 7 and 281.6 % at day 10. More importantly, Saos-2 cells could grow, proliferate, and infiltrate into the scaffold. Therefore, this 3D PLLA/PCL with BG sponge holds great promise for bone defect repair in tissue engineering applications.

Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects.

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties, biocompatibility, biodegradability, vasculogenic ability and osteo-inductivity. The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma (PRP)-loaded gelatin methacrylate (GM) and employ them for the regeneration of large-sized bone defects. We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors (GFs) from hydrogels. The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects. For biofunction assay, the GM@PRP hydrogels significantly improved cell migration and angiogenesis. Especially, transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels. The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats. Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis, biomineralization, and collagen deposition. Based on the biocompatibility and biological function of GM@PRP hydrogels, a new strategy is provided for the regenerative repair of large-size bone defects.

Hierarchical porous PLLA/ACP fibrous membrane towards bone tissue scaffold.

Electrospun fibres have emerged as vital components in developing tissue engineering scaffolds. Calcium phosphate-based materials, renowned for their bioactivity and biocompatibility, have garnered considerable attention in biomedical applications. This study focuses on the incorporation of amorphous calcium phosphate (ACP) nanoparticles into poly(L-lactic acid) (PLLA) to produce electrospun PLLA/ACP fibrous membranes. Subsequent treatment with acetone yielded a hierarchical porous structure, boasting an ultra-high surface area of 94.7753 ± 0.3884 m2/g. The ACP nanoparticles, initially encapsulated by PLLA, were exposed on the fibre surface after acetone treatment. Furthermore, the porous PLLA/ACP fibrous membrane exhibited superior mechanical properties (Young's modulus = 0.148 GPa, tensile strength = 3.05 MPa) and enhanced wettability. In a 7-day in vitro cell culture with human osteoblast-like cells, the porous PLLA/ACP fibrous membrane demonstrated a significant improvement in osteoblast adhesion and proliferation, with a proliferation rate increase of 252.0% and 298.7% at day 4 and day 7, respectively. These findings underscore the potential of the porous PLLA/ACP fibrous membrane as a promising candidate for bone tissue scaffolds.

Advanced Bioresin Formulation for 3D-Printed Bone Scaffolds: PCLDMA and p-PLA Integration.

In bone tissue engineering, scaffold attributes such as pore dimensions and mechanical strength are crucial. This study synthesized polycaprolactone dimethacrylate (PCLDMA) from polycaprolactone (PCL), incorporating epichlorohydrin (Epi-PCL) and methacryloyl chloride (Meth-Cl). PCLDMA was blended with polylactic acid (p-PLA) to 3D-print bone scaffolds using stereolithography (SLA). Analytical techniques included nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and compression testing. Degradation kinetics and cell viability were investigated using human osteoblast (HOB) cells. Findings revealed PCLDMA/p-PLA composite scaffold superiority over the original polymers. Notably, PCLDMA-60 (60% PCLDMA, 40% p-PLA) displayed optimal properties. Compressive strength varied from 0.019 to 16.185 MPa, porosity from 2% to 50%, and degradation rates from 0% to 0.4% over three days. Cell viability assays affirmed biocompatibility across various PCLDMA ratios. In conclusion, PCLDMA/p-PLA composite scaffolds, particularly PCLDMA-60, show great potential in bone tissue engineering.

3D printed polylactic acid-based nanocomposite scaffold stuffed with microporous simvastatin-loaded polyelectrolyte for craniofacial reconstruction.

Critical sized craniofacial defects are among the most challenging bone defects to repair, due to the anatomical complexity and aesthetic importance. In this study, a polylactic acid/hardystonite-graphene oxide (PLA/HTGO) scaffold was fabricated through 3D printing. In order to upgrade the 3D printed scaffold to a highly porous scaffold, its channels were filled with pectin-quaternized chitosan (Pec-QCs) polyelectrolyte solution containing 0 or 20 mg/mL of simvastatin (Sim) and then freeze-dried. These scaffolds were named FD and FD-Sim, respectively. Also, similar PLA/HTGO scaffolds were prepared and dip coated with Pec-QCs solution containing 0 or 20 mg/mL of Sim and were named DC and DC-Sim, respectively. The formation of macro/microporous structure was confirmed by morphological investigations. The release of Sim from DC-Sim and FD-Sim scaffolds after 28 days was measured as 77.40 ± 5.25 and 86.02 ± 3.63 %, respectively. Cytocompatibility assessments showed that MG-63 cells had the highest proliferation, attachment and spread on the Sim containing scaffolds, especially FD-Sim. In vivo studies on a rat calvarial defect model revealed that an almost complete recovery occurred in the group treated with FD-Sim scaffold after 8 weeks and the defect was filled with newly formed bone. The results of this study acknowledge that the FD-Sim scaffold can be a perfect candidate for calvarial defect repair.

Safety and Efficacy of a Novel Polyglycolic Acid Meniscal Scaffold for Irreparable Meniscal Tear.

OBJECTIVE: Meniscal tears treated with a partial meniscectomy could induce knee osteoarthritis, thereby altering or damaging knee kinetics and biomechanics. We have developed a meniscal scaffold made of polyglycolic acid (PGA) coated with polylactic acid/caprolactone (PGA scaffold), which could induce new tissue growth of meniscus-like tissue. This study aimed to evaluate the safety and efficacy of a novel meniscal scaffold for the treatment of irreparable meniscal injuries. DESIGN: This study describes the findings of a cyclic torque test and first clinical trial of a PGA scaffold for inducing meniscus-like tissue in humans. As the first step, biomechanical testing of the PGA scaffold was performed using a cyclic torque test. Six patients underwent arthroscopic implantation of the PGA scaffold. Furthermore, the patients underwent preoperative clinical, serological, radiographic, and magnetic resonance imaging examinations at 3, 6, and 12 months postoperatively. The patients also underwent a second-look arthroscopy 12 months after implantation. RESULTS: Torque increased with increasing cyclic loading. However, no structural damage to the sample was noted after 70,000 loading cycles. All patients showed improvement in pain, Lysholm scores, Tegner activity scores, International Knee Documentation Committee, and knee injury and osteoarthritis outcome. The second-look arthroscopy revealed that meniscal tissue had regenerated in 5 patients (83%). Radiography and magnetic resonance imaging confirmed no progression of degenerative joint disease. CONCLUSIONS: The PGA scaffold could tolerate shear forces, did not produce safety concerns, and may have therapeutic potentials for irreparable meniscal tears in humans.

Application of Nondegradable Synthetic Materials for Tendon and Ligament Injury.

Tendon and ligament injuries, prevalent requiring surgical intervention, significantly impact joint stability and function. Owing to excellent mechanical properties and biochemical stability, Nondegradable synthetic materials, including polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE), have demonstrated significant potential in the treatment of tendon and ligament injuries. These above materials offer substantial mechanical support, joint mobility, and tissue healing promotion of the shoulder, knee, and ankle joint. This review conclude the latest development and application of nondegradable materials such as artificial patches and ligaments in tendon and ligament injuries including rotator cuff tears (RCTs), anterior cruciate ligament (ACL) injuries, and Achilles tendon ruptures.

Aptamer-enriched scaffolds for tissue regeneration: a systematic review of the literature.

Introduction: Aptamers are a brand-new class of receptors that can be exploited to improve the bioactivity of tissue engineering grafts. The aim of this work was to revise the current literature on in vitro and in vivo studies in order to i) identify current strategies adopted to improve scaffold bioactivity by aptamers; ii) assess effects of aptamer functionalization on cell behavior and iii) on tissue regeneration. Methods: Using a systematic search approach original research articles published up to 30 April 2022, were considered and screened. Results: In total, 131 records were identified and 18 were included in the final analysis. Included studies showed that aptamers can improve the bioactivity of biomaterials by specific adsorption of adhesive molecules or growth factors from the surrounding environment, or by capturing specific cell types. All the studies showed that aptamers ameliorate scaffold colonization by cells without modifying the physicochemical characteristics of the bare scaffold. Additionally, aptamers seem to promote the early stages of tissue healing and to promote anatomical and functional regeneration. Discussion: Although a metanalysis could not be performed due to the limited number of studies, we believe these findings provide solid evidence supporting the use of aptamers as a suitable modification to improve the bioactivity of tissue engineering constructs.

Melt electrowriting of a biocompatible photo-crosslinkable poly(D,L-lactic acid)/poly(ε-caprolactone)-based material with tunable mechanical and functionalization properties.

The use of polymeric biomaterials to create tissue scaffolds using additive manufacturing techniques is a well-established practice, owing to the incredible rapidity and complexity in design that modern 3D printing methods can provide. One frontier approach is melt electrowriting (MEW), a technique that takes advantage of electrohydrodynamic phenomena to produce fibers on the scale of 10's of microns with designs capable of high resolution and accuracy. Poly(ε-caprolactone) (PCL) is a material that is commonly used in MEW due to its favorable thermal properties, high stability, and biocompatibility. However, one of the drawbacks of this material is that it lacks the necessary chemical groups which allow covalent crosslinking of additional elements onto its structure. Attempts to functionalise PCL structures therefore often rely on the functional units to be applied externally via coatings or integrally mixed elements. Both can be extremely useful depending on their applications, but can add extra difficulties into the use of the resulting structures. Coatings require careful design and application to prevent rapid degradation, while elements mixed into the polymer melt must deal with the possibilities of phase separation and changes to MEW properties of the unadulterated polymer. With this in mind, this study sought to imbibe functionality to MEW-printed scaffolds using the approach of adding functional units directly, via covalent bonding of functional groups to the polymer itself. To this end, this study employs a recently developed class of polymers called acrylate-endcapped urethane-based polymers (AUPs). The polymer backbone of the specific AUP used consists of a poly(D,L-lactic acid) (PDLLA)/PCL copolymer chain, which is functionalized with 6 acrylate groups, 3 at either end. Through blending of the AUP with PCL, various concentrations of this mixture were used with MEW to produce scaffolds that possessed acrylate groups on their surface. Using UV crosslinking, these groups were tagged with Fluorescein-o-Acrylate to verify that PDLLA/PCL AUP/PCL blends facilitate the direct covalent bonding of external agents directly onto the MEW material. Blending of the AUP with PCL increases the scaffold's stiffness and ultimate strength. Finally, blends were proven to be highly biocompatible, with cells attaching and proliferating readily at day 3 and 7 post seeding. Through this work, PDLLA/PCL AUP/PCL blends clearly demonstrated as a biocompatible material that can be processed using MEW to create functionalised tissue scaffolds.

Three-dimensional, label-free cell viability measurements in tissue engineering scaffolds using optical coherence tomography.

In the field of tissue engineering, 3D scaffolds and cells are often combined to yield constructs that are used as therapeutics to repair or restore tissue function in patients. Viable cells are often required to achieve the intended mechanism of action for the therapy, where the live cells may build new tissue or may release factors that induce tissue regeneration. Thus, there is a need to reliably measure cell viability in 3D scaffolds as a quality attribute of a tissue-engineered medical product. Here, we developed a noninvasive, label-free, 3D optical coherence tomography (OCT) method to rapidly (2.5 min) image large sample volumes (1 mm3 ) to assess cell viability and distribution within scaffolds. OCT imaging was assessed using a model scaffold-cell system consisting of a polysaccharide-based hydrogel seeded with human Jurkat cells. Four test systems were used: hydrogel seeded with live cells, hydrogel seeded with heat-shocked or fixed dead cells and hydrogel without any cells. Time series OCT images demonstrated changes in the time-dependent speckle patterns due to refractive index (RI) variations within live cells that were not observed for pure hydrogel samples or hydrogels with dead cells. The changes in speckle patterns were used to generate live-cell contrast by image subtraction. In this way, objects with large changes in RI were binned as live cells. Using this approach, on average, OCT imaging measurements counted 326 ± 52 live cells per 0.288 mm3 for hydrogels that were seeded with 288 live cells (as determined by the acridine orange-propidium iodide cell counting method prior to seeding cells in gels). Considering the substantial uncertainties in fabricating the scaffold-cell constructs, such as the error from pipetting and counting cells, a 13% difference in the live-cell count is reasonable. Additionally, the 3D distribution of live cells was mapped within a hydrogel scaffold to assess the uniformity of their distribution across the volume. Our results demonstrate a real-time, noninvasive method to rapidly assess the spatial distribution of live cells within a 3D scaffold that could be useful for assessing tissue-engineered medical products.

Osteoregenerative Potential of 3D-Printed Poly ε-Caprolactone Tissue Scaffolds In Vitro Using Minimally Manipulative Expansion of Primary Human Bone Marrow Stem Cells.

The repair of orthopedic and maxillofacial defects in modern medicine currently relies heavily on the use of autograft, allograft, void fillers, or other structural material composites. This study examines the in vitro osteo regenerative potential of polycaprolactone (PCL) tissue scaffolding, fabricated via a three-dimensional (3D) additive manufacturing technology, i.e., a pneumatic micro extrusion (PME) process. The objectives of this study were: (i) To examine the innate osteoinductive and osteoconductive potential of 3D-printed PCL tissue scaffolding and (ii) To perform a direct in vitro comparison of 3D-printed PCL scaffolding with allograft Allowash® cancellous bone cubes with regards to cell-scaffold interactions and biocompatibility with three primary human bone marrow (hBM) stem cell lines. This study specifically examined cell survival, cell integration, intra-scaffold cell proliferation, and differentiation of progenitor cells to investigate the potential of 3D-printed PCL scaffolds as an alternative to allograft bone material for the repair of orthopedic injuries. We found that mechanically robust PCL bone scaffolds can be fabricated via the PME process and the resulting material did not elicit detectable cytotoxicity. When the widely used osteogenic model SAOS-2 was cultured in PCL extract medium, no detectable effect was observed on cell viability or proliferation with multiple test groups showing viability ranges of 92.2% to 100% relative to a control group with a standard deviation of ±10%. In addition, we found that the honeycomb infill pattern of the 3D-printed PCL scaffold allowed for superior mesenchymal stem-cell integration, proliferation, and biomass increase. When healthy and active primary hBM cell lines, having documented in vitro growth rates with doubling times of 23.9, 24.67, and 30.94 h, were cultured directly into 3D-printed PCL scaffolds, impressive biomass increase values were observed. It was found that the PCL scaffolding material allowed for biomass increase values of 17.17%, 17.14%, and 18.18%, compared to values of 4.29% for allograph material cultured under identical parameters. It was also found that the honeycomb scaffold infill pattern was superior to the cubic and rectangular matrix structures, and provided a superior microenvironment for osteogenic and hematopoietic progenitor cell activity and auto-differentiation of primary hBM stem cells. Histological and immunohistochemical studies performed in this work confirmed the regenerative potential of PCL matrices in the orthopedic setting by displaying the integration, self-organization, and auto-differentiation of hBM progenitor cells within the matrix. Differentiation products including mineralization, self-organizing "proto-osteon" structures, and in vitro erythropoiesis were observed in conjunction with the documented expression of expected bone marrow differentiative markers including CD-99 (>70%), CD-71 (>60%), and CD-61 (>5%). All of the studies were conducted without the addition of any exogenous chemical or hormonal stimulation and exclusively utilized the abiotic and inert material polycaprolactone; setting this work apart from the vast majority of contemporary investigations into synthetic bone scaffold fabrication In summary, this study demonstrates the unique clinical potential of 3D-printed PCL scaffolds for stem cell expansion and incorporation into advanced microstructures created via PME manufacturing to generate a physiologically inert temporary bony defect graft with significant autograft features for enhanced end-stage healing.

Evaluation of porous bacterial cellulose produced from foam templating with different additives and its application in 3D cell culture.

Bacterial cellulose (BC) is used in biomedical applications due to its unique material properties such as mechanical strength with a high water-absorbing capacity and biocompatibility. Nevertheless, native BC lacks porosity control which is crucial for regenerative medicine. Hence, developing a simple technique to change the pore sizes of BC has become an important issue. This study combined current foaming BC (FBC) production with incorporation of different additives (avicel, carboxymethylcellulose, and chitosan) to form novel porous additive-altered FBC. Results demonstrated that the FBC samples provided greater reswelling rates (91.57 % ~ 93.67 %) compared to BC samples (44.52 % ~ 67.5 %). Moreover, the FBC samples also showed excellent cell adhesion and proliferation abilities for NIH-3T3 cells. Lastly, FBC allowed cells to penetrate to deep layers for cell adhesion due to its porous structure, providing a competitive scaffold for 3D cell culture in tissue engineering.

Additive manufacturing of PLA-Mg composite scaffolds for hard tissue engineering applications.

Polylactic acid (PLA) is considered as a great option to be employed as 3D porous scaffold in hard tissue engineering applications owing to its excellent biocompatibility and processability. However, relatively weak mechanical properties and inappropriate biodegradability limit its extensive usage. In order to overcome the mentioned challenges, micrometric magnesium particles were incorporated into the PLA matrix by the fused deposition modeling (FDM) technique. The effects of various Mg contents (i.e., 2, 4, 6, 8 and 10 wt%) on the structural, thermal, rheological, mechanical, wettability, degradability characteristics and cellular behavior of the 3D porous PLA-Mg composite scaffolds were examined. The developed PLA-Mg composites exhibit an interconnected porous structure with a mostly uniform distribution of Mg particles in the PLA matrix. It was found that incorporation of Mg particles into the PLA matrix enhances the mechanical, physical, chemical and biological characteristics of PLA. The cell studies demonstrate that the PLA-6Mg composite scaffold provides the best cellular response in terms of cell atachment and viability. The obtained results in this investigation greatly suggest that the 3D-printed PLA-Mg composite scaffold is a promising candidate for hard tissue engineering applications.

Nondeterministic multiobjective optimization of 3D printed ceramic tissue scaffolds.

Despite significant advances in the design optimization of bone scaffolds for enhancing their biomechanical properties, the functionality of these synthetic constructs remains suboptimal. One of the main challenges in the structural optimization of bone scaffolds is associated with the large uncertainties caused by the manufacturing process, such as variations in scaffolds' geometric features and constitutive material properties after fabrication. Unfortunately, such non-deterministic issues have not been considered in the existing optimization frameworks, thereby limiting their reliability. To address this challenge, a novel multiobjective robust optimization approach is proposed here such that the effects of uncertainties on the optimized design can be minimized. This study first conducted computational analyses of a parameterized ceramic scaffold model to determine its effective modulus, structural strength, and permeability. Then, surrogate models were constructed to formulate explicit mathematical relationships between the geometrical parameters (design variables) and mechanical and fluidic properties. The Non-Dominated Sorting Genetic Algorithm II (NSGA-II) was adopted to generate the robust Pareto solutions for an optimal set of trade-offs between the competing objective functions while ensuring the effects of the noise parameters to be minimal. Note that the nondeterministic optimization of tissue scaffold presented here is the first of its kind in open literature, which is expected to shed some light on this significant topic of scaffold design and additive manufacturing in a more realistic way.

Satisfactory clinical outcomes with autologous matrix-induced chondrogenesis in the treatment of grade IV chondral injuries of the knee.

OBJECTIVE: The research aims to evaluate short- and medium-term outcomes of patients treated using autologous matrix-induced chondrogenesis (AMIC) with a hyaluronic acid scaffold (Hyalofast, Anika Therapeutics, MA, USA) in grade IV chondral lesions according to the Outerbridge classification in the knee. METHODS: This is a multicentre, non-randomized, retrospective study conducted between 2017 and 2022. To determine the clinical outcome of the patients, the follow-up was done with the subjective International Knee Documentation Committee (IKDC) score, pre-surgery, and with a follow-up at 12, 24, and 32 months. RESULTS: Fifty patients (28 female) with a mean age of 45.9 ± 12.7 years were recruited. The mean size of the lesion was 3.5 cm2, and the injuries located in the patella (30%) and trochlear groove (24%) were the most frequent. The total IKDC clinical score significantly increased from baseline to the 32 months of follow-up with a mean difference of 36.4 (95% CI, 29.1-43.7, p < 0.001). Besides, there was a statistically significant improvement in all categories of the IKDC (symptoms, sports activities, function, and activity of daily living) compared between pre-surgery and 24 and 32 months of follow-up. The patients younger than 45 years presented better clinical outcomes than older ones with a difference between medians of 10.40 (95% CI, 1.10-11.50, p = 0.0247), and a negative correlation was found between the 32-month IKDC score and the age. In addition, no statistically significant difference was found when comparing the last results of the IKDC between patients with and without associated surgical procedures or between patients with single and several lesions, neither nor between men and women. The level of satisfaction with the procedure of all the patients, on a score of 1-10, was on average 8 ± 1.5. CONCLUSION: Results of this study indicate that patients who underwent the AMIC procedure with hyaluronic acid scaffold for the treatment of grade IV chondral lesions in the knee presented satisfactory results throughout the follow-up. LEVEL OF EVIDENCE: Level IV.

Measuring dimensionality of cell-scaffold contacts of primary human bone marrow stromal cells cultured on electrospun fiber scaffolds.

The properties and structure of the cellular microenvironment can influence cell behavior. Sites of cell adhesion to the extracellular matrix (ECM) initiate intracellular signaling that directs cell functions such as proliferation, differentiation, and apoptosis. Electrospun fibers mimic the fibrous nature of native ECM proteins and cell culture in fibers affects cell shape and dimensionality, which can drive specific functions, such as the osteogenic differentiation of primary human bone marrow stromal cells (hBMSCs), by. In order to probe how scaffolds affect cell shape and behavior, cell-fiber contacts were imaged to assess their shape and dimensionality through a novel approach. Fluorescent polymeric fiber scaffolds were made so that they could be imaged by confocal fluorescence microscopy. Fluorescent polymer films were made as a planar control. hBSMCs were cultured on the fluorescent substrates and the cells and substrates were imaged. Two different image analysis approaches, one having geometrical assumptions and the other having statistical assumptions, were used to analyze the 3D structure of cell-scaffold contacts. The cells cultured in scaffolds contacted the fibers in multiple planes over the surface of the cell, while the cells cultured on films had contacts confined to the bottom surface of the cell. Shape metric analysis indicated that cell-fiber contacts had greater dimensionality and greater 3D character than the cell-film contacts. These results suggest that cell adhesion site-initiated signaling could emanate from multiple planes over the cell surface during culture in fibers, as opposed to emanating only from the cell's basal surface during culture on planar surfaces.

Additive Manufacturing of Polymer/Mg-Based Composites for Porous Tissue Scaffolds.

Due to their commercial availability, superior processability, and biocompatibility, polymers are frequently used to build three-dimensional (3D) porous scaffolds. The main issues limiting the widespread clinical use of monophasic polymer scaffolds in the bone healing process are their inadequate mechanical strength and inappropriate biodegradation. Due to their mechanical strength and biocompatibility, metal-based scaffolds have been used for various bone regenerative applications. However, due to the mismatch in mechanical properties and nondegradability, they lack integration with the host tissues, resulting in the production of fiber tissue and the release of toxic ions, posing a risk to the durability of scaffolds. Due to their natural degradability in the body, Mg and its alloys increasingly attract attention for orthopedic and cardiovascular applications. Incorporating Mg micro-nano-scale particles into biodegradable polymers dramatically improves scaffolds and implants' strength, biocompatibility, and biodegradability. Polymer biodegradable implants also improve the quality of life, particularly for an aging society, by eliminating the secondary surgery often needed to remove permanent implants and significantly reducing healthcare costs. This paper reviews the suitability of various biodegradable polymer/Mg composites for bone tissue scaffolds and then summarizes the current status and challenges of polymer/magnesium composite scaffolds. In addition, this paper reviews the potential use of 3D printing, which has a unique design capability for developing complex structures with fewer material waste at a faster rate, and with a personalized and on-site fabrication possibility.