Controllable Degradation Rate Research Articles

Harnessing the power of polyol-based polyesters for biomedical innovations: synthesis, properties, and biodegradation.

Polyesters based on polyols have emerged as promising biomaterials for various biomedical applications, such as tissue engineering, drug delivery systems, and regenerative medicine, due to their biocompatibility, biodegradability, and versatile physicochemical properties. This review article provides an overview of the synthesis methods, performance, and biodegradation mechanisms of polyol-based polyesters, highlighting their potential for use in a wide range of biomedical applications. The synthesis techniques, such as simple polycondensation and enzymatic polymerization, allow for the fine-tuning of polyester structure and molecular weight, thereby enabling the tailoring of material properties to specific application requirements. The physicochemical properties of polyol-based polyesters, such as hydrophilicity, crystallinity, and mechanical properties, can be altered by incorporating different polyols. The article highlights the influence of various factors, such as molecular weight, crosslinking density, and degradation medium, on the biodegradation behavior of these materials, and the importance of understanding these factors for controlling degradation rates. Future research directions include the development of novel polyesters with improved properties, optimization of degradation rates, and exploration of advanced processing techniques for fabricating scaffolds and drug delivery systems. Overall, polyol-based polyesters hold significant potential in the field of biomedical applications, paving the way for groundbreaking advancements and innovative solutions that could revolutionize patient care and treatment outcomes.

Hydrogel-based delivery system applied in the local anti-osteoporotic bone defects.

Osteoporosis is an age-related systemic skeletal disease leading to bone mass loss and microarchitectural deterioration. It affects a large number of patients, thereby economically burdening healthcare systems worldwide. The low bioavailability and complications, associated with systemic drug consumption, limit the efficacy of anti-osteoporosis drugs currently available. Thus, a combination of therapies, including local treatment and systemic intervention, may be more beneficial over a singular pharmacological treatment. Hydrogels are attractive materials as fillers for bone injuries with irregular shapes and as carriers for local therapeutic treatments. They exhibit low cytotoxicity, excellent biocompatibility, and biodegradability, and some with excellent mechanical and swelling properties, and a controlled degradation rate. This review reports the advantages of hydrogels for adjuvants loading, including nature-based, synthetic, and composite hydrogels. In addition, we discuss functional adjuvants loaded with hydrogels, primarily focusing on drugs and cells that inhibit osteoclast and promote osteoblast. Selecting appropriate hydrogels and adjuvants is the key to successful treatment. We hope this review serves as a reference for subsequent research and clinical application of hydrogel-based delivery systems in osteoporosis therapy.

Zein-based injectable biomaterial and angiogenic activity through peptides produced by enzymatic degradation

Injectable biomaterials are gaining attention due to minimal invasiveness and precise implantation in deep anatomical locations. For tissue regeneration, controlling the degradation and improving vascularization are still the key issues to be resolved. Moreover, for protein-based biomaterials, immune response should be specially considered, although they have advantages such as biodegradability, their degraded products have innate bioactivity and can be utilized by our body. Zein, a plant protein, has been explored for biomedical applications. Recently, we have reported zein gel as a 3D printing ink for drug delivery systems. In this study, we extended the application of zein gel as an injectable biomaterial. Zein gels showed shear-thinning property and tunable yield stress, which is essential for injectability and shape adaptability. Polyvinylpyrrolidone (PVP) was added to the gel to accelerate the degradation and subsequently generate more bioactive peptides for their anti-inflammatory and angiogenic functions as evidenced by in vitro evaluation. Animal experiment using Sprague Dawley (SD) rats also showed a positive angiogenic response after subcutaneous implantation of zein gels with PVP. Bioactive peptides produced from zein degradation were responsible for the angiogenic response that was validated by adding zein degraded products to the gel. Overall, zein gel was proven a promising injectable biomaterial that can fill tissue defect and improve tissue regeneration with controllable degradation rate. Moreover, the enzyme-treated zein hydrolysates can be used as additives with angiogenic activity.

Porous Silicon Microneedles for Enhanced Transdermal Drug Delivery

AbstractThe transdermal route is attractive for the minimally invasive administration of small and large molecules. Microneedles (MNs) are particularly promising because of their straightforward, cost‐effective, and safe administration. But precise control over their degradation rate within the skin remains a challenge. Here, porous silicon microneedles (pSi MNs) with controlled degradation rate, tunable porosity, high payload capacity, and mechanical stability are introduced for transdermal delivery of bioactive molecules. pSi MNs are fabricated by combining dry and wet etching methods. After creating MNs via deep reactive ion etching, a porous surface is obtained by electrochemical anodization, producing pSi MNs of about 42 µm length, tip diameter < 1 µm, and conformal porous layers. The biodegradability and the mechanical properties of pSi MNs are adjusted by changing the thickness of the porous layer from 1.5 to 4.0 µm. Both small and macromolecular drug molecules are uniformly loaded into the porous layer of the pSi MN arrays. Ex vivo penetration experiments on porcine tissue demonstrate efficient transdermal delivery using pSi MNs. The novel pSi MNs with tunable porosity, biodegradability, and mechanical strength offer opportunities for the delivery of biotherapeutics through the skin, engendering innovations in pharmaceutical sciences.

In Vitro Degradation Behavior, Mechanical Properties, and Cytocompatibility of Biodegradable Mg-1Zn-xSn Alloys

The application of biodegradable alloys in orthopedic implants has gained widespread attention globally. Magnesium alloys with controllable degradation rate and suitable mechanical properties have been regarded as potential orthopedic implant material. In this paper, a Mg-1Zn-xSn (x = 0, 1.0, 1.5, 2.0 wt.%) ternary alloy was designed and its performance was investigated. Compared with the Mg-1Zn alloy, the Mg-1Zn-xSn alloys showed enhanced mechanical properties and in vitro degradation performance. Above all, the extruded Mg-1Zn-1.0Sn alloy exhibited an extremely low corrosion rate of 0.12 mm/y with a low hydrogen release of 0.021 mL/cm2/day, which can be attributed to the hydrogen release suppression effect caused by Sn and SnO2 formation in the surface of the alloy. The cytotoxicity of the Mg-1Zn-1.0Sn alloy was evaluated by the cell counting kit-8 (CCK-8) method, the results of which show that its cytotoxicity grade is zero, and the MC3T3-E1 cells spread well on the alloy surface. The findings in this paper demonstrated that Mg-1Zn-1.0Sn is a potential candidate for biodegradable material in the orthopedic implant field.

Porous synthetic hydrogel carrying basic fibroblast growth factor with controllable and rapid degradation rate to promote wound healing

Porous hydrogel dressings show breathability and possibility to carry and release basic fibroblast growth factor (bFGF) to promote wound healing. However, the difficult replacement may lead to the secondary damage. Thus, there is an urgent need to develop a method platform to control the degradation rate of hydrogel, so as to realize the on-demand replacement. The present study fabricated a porous hydrogel from co-polymized N,N′-bis(acryloyl) cystamine (BAC), allyl polyethylene glycol 500 (APEG500) and acrylic acid (AA) with the presence of polycaprolactone (PCL). BAC contains disulfide bond, which crosslinked the hydrogel. The pore size of the porous hydrogel was 400–600 μm. Higher content of BAC indicated higher crosslinking density, which reduced swelling ratio of hydrogel, while promoted hydrogel storage modulus. At the same time, the presence of PCL reduced swelling ratio of hydrogel, while promoted hydrogel mechanical properties, endowing hydrogel with tough feature. Porous hydrogels that crosslinked by disulfide bonds immersed in glutathione solution were found to degrade spontaneously and quickly due to the response to glutathione. Both crosslinking density and PCL content affected the degradation rate. The porous hydrogel carrying bFGF was applied to wound, promoting angiogenesis, thus accelerating wound healing within 12 d. Due to the spontaneous and rapid degradation of optimized porous hydrogel on wound within 3 days, there was no operation of removing dressing during treatment, avoiding damage during dressing replacement.

Physicochemical and cytotoxicity studies of a novel hydrogel nanoclay EPD coating on titanium made of chitosan/gelatin/halloysite for biomedical applications

This recent study proposes a novel three-dimensional hydrogel nanoclay coating, referred to as microbeads-nanotubes (MNTs size: bead, Ø 1–15 μm; tube, Ø 30–70 nm) deposited on commercially pure titanium (cpTi). The proposed MNTs particles were electrophoretically co-deposited (EPD: 10 V, 5 min, 25 mA/cm2) on cpTi with the chitosan/gelatin hydrogel matrix. The resulting hydrogel nanoclay coating has a homogeneous web-like micronetwork morphology and is highly porous (Ø ca. 100–200 μm) in structure, intertwined with nanotube tunnelling (Ø 30–70 nm). The incorporation of MNTs particles within the web-like micro-network of dried hydrogel on cpTi reduces the coating's swelling in PBS and leads to a controlled degradation rate in Lysozyme solution. It also increased the hydrogel coating’ corrosion current resistance and induced osteoblast viability. The fabrication of the proposed nanoclay hydrogel from a mixture of chitosan/gelatin/halloysite as colloids and MNTs particles in this recent study is fast and straightforward. The nontoxic property of the MNT coating established in this report could broaden and diversify the hydrogel nanoclay material applications for implant coatings and medication nanocontainers in the near future.

Degradation Mode of PBAT Mulching Film and Control Methods During its Degradation Induction Period

: Plastic films play an important role in China's agricultural production. However, the large-scale use of plastic film has also caused very serious agricultural film pollution. Biodegradable polymers have received much attention because of the environmental pollution caused by the traditional plastic mulching film. The most typical copolymer is poly (butylene adipate co butylene terephthalate) (PBAT). Poly (Butylene Adipate-co-Terephthalate) (PBAT) is a kind of aliphaticaromatic polyester with excellent biodegradability and mechanical processing properties. Therefore, it has been rapidly developed and widely used in the industry. However, the degradation period of the agricultural film depends on certain requirements. Currently, the degradable materials available in the market do not meet the needs of all crops due to their degradation period. In this paper, the basic properties, degradation process and methods to delay the degradation of PBAT are reviewed for improving the degradation period of the plastic film that is prepared by using this kind of material. The degradation process includes photodegradation, biodegradation, and hydrolysis. The methods of delaying the degradation process include adding a chain extender, light stabilizer, antihydrolysis agent and antibacterial agent, providing a theoretical basis for the research and development of biodegradable film with a controllable degradation cycle. The future research and development of biodegradable polymers will mainly focus on controllable degradation rate, stable degradation cycle, new materials, and reducing research and development costs.

Synthesis of Antibacterial Hybrid Hydroxyapatite/Collagen/Polysaccharide Bioactive Membranes and Their Effect on Osteoblast Culture.

Inspired by the composition and confined environment provided by collagen fibrils during bone formation, this study aimed to compare two different strategies to synthesize bioactive hybrid membranes and to assess the role the organic matrix plays as physical confinement during mineral phase deposition. The hybrid membranes were prepared by (1) incorporating calcium phosphate in a biopolymeric membrane for in situ hydroxyapatite (HAp) precipitation in the interstices of the biopolymeric membrane as a confined environment (Methodology 1) or (2) adding synthetic HAp nanoparticles (SHAp) to the freshly prepared biopolymeric membrane (Methodology 2). The biopolymeric membranes were based on hydrolyzed collagen (HC) and chitosan (Cht) or κ-carrageenan (κ-carr). The hybrid membranes presented homogeneous and continuous dispersion of the mineral particles embedded in the biopolymeric membrane interstices and enhanced mechanical properties. The importance of the confined spaces in biomineralization was confirmed by controlled biomimetic HAp precipitation via Methodology 1. HAp precipitation after immersion in simulated body fluid attested that the hybrid membranes were bioactive. Hybrid membranes containing Cht were not toxic to the osteoblasts. Hybrid membranes added with silver nanoparticles (AgNPs) displayed antibacterial action against different clinically important pathogenic microorganisms. Overall, these results open simple and promising pathways to develop a new generation of bioactive hybrid membranes with controllable degradation rates and antimicrobial properties.

Advancing standard techniques for treatment of perianal fistula; when tissue engineering meets seton

Tissue engineering is a promising field for treating various diseases using tissue-like structures generated through biomaterials, scaffolds, nanoparticles, biomolecules, and stem cells. This advanced method is considered one of the next-generation therapeutic techniques that may solve the therapeutic challenges in treating perianal fistula based on seton therapy. Remarkable advances in stem cell biology, genetics, biomaterials, fabrication technologies, and nanotechnology have provided the opportunity to implement this multidisciplinary approach to repair damaged tissue in the seton-based fistula treatment. In addition, tissue engineering provides us with nanostructured biomaterials to fabricate setons that can act as scaffolds, with modified mechanical and biological properties such as antibacterial and anti-inflammatory. This review focuses on the applications, advantages, and future perspectives of tissue engineering to enhance the seton placement techniques and present a novel therapeutic solution to treat perianal fistula. In addition, in vivo and in vitro studies about implementing tissue engineering in the treatment of perianal fistula are reported in this study. Also, it summarizes the surgical procedures for the treatment of fistula, including Ligation of the Intersphincteric Fistula Tract (LIFT), Fistula Laser Closure (FiLaC™), Over-The-Scope Clip System (OTSC), Video-assisted anal fistula treatment (VAAFT), Anal fistula plug (AFP), and Rectal advancement flap (RAF). Furthermore, the applications and properties of different setons including, cutting setons (Penrose drains, rubber band, polypropylene, and silk), non-cutting setons (loose, knot-free, Comfort, and Super Seton®), and chemical setons (Ksharasutra) are described. In the end, we present the challenges and future trends of implementing tissue engineering technology in the seton-based therapy for the treatment of perianal fistula. The applications of tissue engineering in seton-based fistula therapy. The scaffolds with controllable mechanical properties and degradation rate can have antibacterial, anti-inflammatory, and drug-releasing properties. Besides, the scaffolds can be incorporated or covered with stem cells to regenerate damaged tissues in the perianal fistula site.

Alkaline Soil Degradation and Crop Safety of 5-Substituted Chlorsulfuron Derivatives.

Sulfonylurea herbicides can lead to serious weed resistance due to their long degradation times and large-scale applications. This is especially true for chlorsulfuron, a widely used acetolactate synthase inhibitor used around the world. Its persistence in soil often affects the growth of crop seedlings in the following crop rotation, and leads to serious environmental pollution all over the world. Our research goal is to obtain chlorsulfuron-derived herbicides with high herbicidal activities, fast degradation times, as well as good crop safety. On account of the slow natural degradation of chlorsulfuron in alkaline soil, based on the previously reported results in acidic soil, the degradation behaviours of 5-substituted chlorsulfuron analogues (L101–L107) were investigated in a soil with pH 8.39. The experimental data indicated that 5-substituted chlorsulfuron compounds could accelerate degradation rates in alkaline soil, and thus, highlighted the potential for rational controllable degradation in soil. The degradation rates of these chlorsulfuron derivatives were accelerated by 1.84–77.22-fold, compared to chlorsulfuron, and exhibited excellent crop safety in wheat and corn (through pre-emergence treatment). In combination with bioassay activities, acidic and alkaline soil degradation, and crop safety, it was concluded that compounds L104 and L107, with ethyl or methyl groups, are potential green sulfonylurea herbicides for pre-emergence treatment on wheat and corn. This paper provides a reference for the further design of new sulfonylurea herbicides with high herbicidal activity, fast, controllable degradation rates, and high crop safety.

Preparation of High Mechanical Strength Chitosan Nanofiber/NanoSiO2/PVA Composite Scaffolds for Bone Tissue Engineering Using Sol-Gel Method.

The majority of chitosan-based bone tissue engineering (BTE) scaffolds have the problem of poor mechanical properties. However, modifying chitosan with conventional silane coupling agents to improve the mechanical properties of scaffolds will introduce additional complications, including cytotoxicity and poor biocompatibility. In this study, two types of organic–inorganic composite scaffolds (F-A-T0/T3/T5 and F-B-T5-P0/P0.5/P1.5/P2.5) were prepared using chitosan nanofibers (CSNF) prepared by the beating-homogenization method, combined with the sol–gel method, and further introduced polyvinyl alcohol (PVA). The F-A-T3 and F-B-T5-P1.5 exhibited interconnected pore and surface nanofibers structures, high porosity (>70%), outstanding swelling properties, and a controllable degradation rate. The Young’s modulus of TEOS: 5.0% (w/w), PVA: 1.5% (w/w) chitosan fiber scaffold is 8.53 ± 0.43 MPa in dry conditions, and 237.78 ± 8.86 kPa in wet conditions, which is four times that of F-A-T5 and twice that of F-B-T5-P0. Additionally, cell (MC3T3-E1) experiments confirmed that the two composite scaffolds had great cytocompatibility and were predicted to be used in the future in the field of BTE scaffolds.

Poly (N-Vinylcaprolactam-Grafted-Sodium Alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation.

This study was aimed to develop novel in situ forming gels based on N-vinylcaprolactam, sodium alginate, and N,N-methylenebisacrylamide. The in situ Poly (NVRCL-g-NaAlg) gels were developed using the cold and free radical polymerization method. The structure formation, thermal stability, and porous nature of gels was confirmed by FTIR, NMR, DSC, TGA, and SEM. The tunable gelation temperature was evaluated by tube titling and rheological analysis. Optical transmittance showed that all formulations demonstrated phase transition around 33 °C. The swelling and release profile showed that gels offered maximum swelling and controlled 5-FU release at 25 °C and pH (7.4), owing to a relaxed state. Porosity and mesh size showed an effect on swelling and drug release. The in vitro degradation profile demonstrated a controlled degradation rate. An MTT assay confirmed that formulations are safe tested against Vero cells. In vitro cytotoxicity showed that 5-FU loaded gels have controlled cytotoxic potential against HeLa and MCF-7 cells (IC50 = 39.91 µg/mL and 46.82 µg/mL) compared to free 5-FU (IC50 = 50.52 µg/mL and 53.58 µg/mL). Histopathological study demonstrated no harmful effects of gels on major organs. The in vivo bioavailability in rabbits showed a controlled release in gel form (Cmax, 1433.59 ± 45.09 ng/mL) compared to a free drug (Cmax, 2263.31 ± 13.36 ng/mL) after the subcutaneous injection.

Poly(lactic acid)/artificially cultured diatom frustules nanofibrous membranes with fast and controllable degradation rates for air filtration.

The worldwide pandemic, coronavirus COVID-19, has been posing a serious threat to the global economy and security in last 2 years. The monthly consumption and subsequent discarding of 129 billion masks (equivalent to 645,000 tons) pose a serious detrimental impact on environmental sustainability. In this study, we report a novel type of nanofibrous membranes (NFMs) with supreme filtration performance and controllable degradation rates, which are mainly composed of polylactic acid (PLA) and artificially cultured diatom frustules (DFs). In this way, the filtration efficiency of particular matter (PM) and the pressure drop were significantly improved in the prepared PLA/DFs NFMs as compared with the neat PLA NFM. In specific, with incorporation of 5% DFs into fibers, PM0.3 removal with a filtration efficiency of over 99% and a pressure drop of 109 Pa were achieved with a membrane thickness of only 0.1 mm. Moreover, the yield strength and crystallinity degree of the PLA/DFs5 NFMs were sharply increased from 1.88 Mpa and 26.37% to 2.72 Mpa and 30.02%. Besides those unique characters, the PLA/DFs5 presented excellent degradability, accompanied by the degradation of 38% in 0.01 M sodium hydroxide solution after 7 days and approximately 100% in natural condition after 42 days, respectively. Meanwhile, the environmentally friendly raw materials of the composite polylactic acid and artificially cultured diatom frustules could be extracted from corn-derived biomass and artificially cultivated diatoms, ensuring the conformance to carbon neutrality and promising applications in personal protection.Graphical abstract Supplementary informationThe online version contains supplementary material available at 10.1007/s42114-022-00474-7.

Size-dependent osteogenesis of black phosphorus in nanocomposite hydrogel scaffolds.

A promising new strategy emerged in bone tissue engineering is to incorporate black phosphorus (BP) into polymer scaffolds, fabricating nanocomposite hydrogel platforms with biocompatibility, degradation controllability, and osteogenic capacity. BP quantum dot is a new concept and stands out recently among the BP family due to its tiny structure and a series of excellent characteristics. In this study, BP was processed into nanosheets of three different sizes via different exfoliation strategies and then incorporated into cross-linkable oligo[poly(ethylene glycol) fumarate] (OPF) to produce nanocomposite hydrogels for bone regeneration. The three different BP nanosheets were designated as BP-L, BP-M, and BP-S, with a corresponding diameter of 242.3±90.0, 107.1±47.9, and 18.8±4.6nm. The degradation kinetics and osteogenic capacity of MC3T3 pre-osteoblasts in vitro were both dependent on the BP size. BP exhibited a controllable degradation rate, which increased with the decrease of the size of the nanosheets, coupled with the release of phosphate in vitro. The osteogenic capacity of the hydrogels was promoted with the addition of all BP nanosheets, compared with OPF hydrogel alone. The smallest BP quantum dots was shown to be optimal in enhancing MC3T3 cell behaviors, including spreading, distribution, proliferation, and differentiation on the OPF hydrogels. These results reinforced that the supplementation of BP quantum dots into OPF nanocomposite hydrogel scaffolds could potentially find application in the restoration of bone defects.

Development of 3D Printed Biodegradable Mesh with Antimicrobial Properties for Pelvic Organ Prolapse.

To address the increasing demand for safe and effective treatment options for pelvic organ prolapse (POP) due to the worldwide ban of the traditional polypropylene meshes, this study introduced degradable polycaprolactone (PCL)/polyethylene glycol (PEG) composite meshes fabricated with melt-electrowriting (MEW). Two PCL/PEG mesh groups: 90:10 and 75:25 (PCL:PEG, wt%) were fabricated and characterized for their degradation rate and mechanical properties, with PCL meshes used as a control. The PCL/PEG composites showed controllable degradation rates by adjusting the PEG content and produced mechanical properties, such as maximal forces, that were higher than PCL alone. The antibacterial properties of the meshes were elicited by coating them with a commonly used antibiotic: azithromycin. Two dosage levels were used for the coating: 0.5 mg and 1 mg per mesh, and both dosage levels were found to be effective in suppressing the growth of S. aureus bacteria. The biocompatibility of the meshes was assessed using human immortalized adipose derived mesenchymal stem cells (hMSC). In vitro assays were used to assess the cell viability (LIVE/DEAD assay), cell metabolic activity (alamarBlue assay) and cell morphology on the meshes (fluorescent and electron microscopy). The cell attachment was found to decrease with increased PEG content. The freshly drug-coated meshes showed signs of cytotoxicity during the cell study process. However, when pre-released for 14 days in phosphate buffered saline, the initial delay in cell attachment on the drug-coated mesh groups showed full recovery at the 14-day cell culture time point. These results indicated that the PCL/PEG meshes with antibiotics coating will be an effective anti-infectious device when first implanted into the patients, and, after about 2 weeks of drug release, the mesh will be supporting cell attachment and proliferation. These meshes demonstrated a potential effective treatment option for POP that may circumvent the issues related to the traditional polypropylene meshes.

Nanostructured hyaluronic acid-based hydrogels encapsulating synthetic/ natural hybrid nanogels as promising wound dressings

Hydrogels with nanostructured morphology formed by embedding polymeric nanoparticles in a biodegradable polymer matrix have gained considerable interest in the medical field due to improved drug delivery profiles and tissue-mimicking architecture. Moreover, through hydrogels biodegradation, the encapsulated nanoparticles are released and can easily enter in different compartments of the body, thus having the potential to control the delivery of short half-life drugs. Therefore, this study was devoted to preparation and characterization of nanostructured hybrid hydrogels by incorporating well-defined maleoyl-chitosan/poly(aspartic acid) (MAC5/PAS) nanogels into a polymer network based on thiolated hyaluronic acid (HASH) for wound dressings applications. The MAC5/PAS nanogels were used not only as nanocarriers for amoxicillin (Amox) encapsulation and control over its release through the HASH hydrogel network, but also as building blocks for hydrogel preparation. The obtained nanocomposite hydrogels exhibited a reduced swelling capacity and a controlled degradation rate in comparison with the non‐filled HASH hydrogel. In vitro release profile revealed the influence of environment pH on Amox delivery, a rapid release of drug being observed at pH 5.4. Moreover, the in vitro and in vivo assays revealed a good biocompatibility of hydrogels, highlighting the potential of these systems as therapeutic scaffolds for dressing applications.

Polycaprolactone usage in additive manufacturing strategies for tissue engineering applications: A review.

Polycaprolactone (PCL) has been extensively applied on tissue engineering because of its low-melting temperature, good processability, biodegradability, biocompatibility, mechanical resistance, and relatively low cost. The advance of additive manufacturing (AM) technologies in the past decade have boosted the fabrication of customized PCL products, with shorter processing time and absence of material waste. In this context, this review focuses on the use of AM techniques to produce PCL scaffolds for various tissue engineering applications, including bone, muscle, cartilage, skin, and cardiovascular tissue regeneration. The search for optimized geometry, porosity, interconnectivity, controlled degradation rate, and tailored mechanical properties are explored as a tool for enhancing PCL biocompatibility and bioactivity. In addition, rheological and thermal behavior is discussed in terms of filament and scaffold production. Finally, a roadmap for future research is outlined, including the combination of PCL struts with cell-laden hydrogels and 4D printing.

The inclusion of leukocytes into platelet rich plasma reduces scaffold stability and hinders extracellular matrix remodelling.

BackgroundScaffolds should have controllable degradation rate and allow cells to produce their own extracellular matrix. Platelet rich plasma (PRP) is a source of autologous growth factors and proteins embedded in a 3D fibrin scaffold. There is no consensus regarding the obtaining conditions and composition of PRPs. The aim of this study was to evaluate how the inclusion of leukocytes (L-PRP) in plasma rich in growth factors (PRGF) may alter the process of fibrinolysis. The effect of different combinations of cellular phenotypes with PRGF and L-PRP clots on both the fibrinolysis and matrix deposition process was also determined. MethodsPRGF and L-PRP clots were incubated for 14 days and D-dimer and type I collagen were determined in their conditioned media to evaluate clots’ stability. For remodelling assays, gingival fibroblasts, alveolar osteoblasts and human umbilical vein endothelial cells (HUVEC) were seeded onto the two types of clots for 14 days. D-dimer, type I collagen, and laminin α4 were measured by ELISA kits in their conditioned media. Morphological and histological analysis were also performed. Cell proliferation was additionally determined ResultsPRGF clots preserved their stability as shown by the low levels of both D-dimer and collagen type I compared to those obtained for L-PRP clots. The inclusion of both gingival fibroblasts and alveolar osteoblasts stimulated a higher fibrinolysis in the PRGF clots. In contrast to this, the degradation rates of both PRGF and L-PRP clots remained unchanged after culturing with the endothelial cells. In all cases, type I collagen and laminin α4 levels were in line with the degree of clots’ degradation. In all phenotypes, cell proliferation was significantly higher in PRGF than in L-PRP clots. ConclusionThe inclusion of leukocytes in PRGF scaffolds reduced their stability, decreased cell number and slowed down cell remodelling.

Fabrication and characterization of biodegradable zinc matrix composites reinforced by uniformly dispersed beta-tricalcium phosphate via graphene oxide-assisted hetero-agglomeration

The development of biodegradable Zn matrix composites has been considered a promising approach to achieving enhanced mechanical properties, controllable degradation rate, good biocompatibility, and good osseointegration as orthopedic implants. However, scant literature regarding Zn matrix composites has been reported because of the great difficulty in dispersing the nano-sized bioactive reinforcements uniformly within the Zn matrix. In the present study, a novel and effective method were employed to obtain Zn matrix composites reinforced by uniformly dispersed beta-tricalcium phosphate (β-TCP) via graphene oxide (GO)-assisted hetero-agglomeration and subsequent spark plasma sintering process. A very low-content (0.04 vol%) few-layered GO was used as a coupling reagent to connect the Zn matrix and nano-sized TCP particles. In an appropriate polarity solvent, the negatively charged GO sheets could combine with both the positively charged Zn powder and TCP particles by electrostatic attraction and charge neutralization. Due to the nature of hetero-agglomeration, the flexible GO sheet could adhere to the large Zn powder and attracted a certain amount of TCP particles to form a Zn/GO/TCP sandwich structure by charge neutralization thereby forming a uniform dispersion of TCP particles within Zn matrix. After the spark plasma sintering (SPS) process, the TCP particles incorporated with very thin ZnO layers (thickness of a few dozen nanometers) formed a homogeneous and unique 3D network-like distribution in as-sintered TCP/Zn composites. A unique “snap pea”-like structure was confirmed at the grain boundary of α-Zn grains, which consisted of the TCP particles as “pea” and thin ZnO layer as “pod”. Due to the uniform dispersion of bioactive TCP particles and unique structure of the TCP incorporating grain boundary, as-sintered 3TCP/Zn matrix composites possessed yield strength (YS) of 140.8 ± 7.7 MPa, failure strain of 36.0 ± 2.8%, the moderate degradation rate of 19.1 ± 3.3 μm·y−1 and good cytocompatibility to MC3T3-E1 cells. Moreover, osteogenic differentiation activity evaluation revealed that the addition of TCP could significantly improve the expressions of the osteogenic differentiation-related gene (ALP) in MC3T3-E1 cells, thereby resulting in improved osteogenic capability. Therefore, biodegradable 3TCP/Zn matrix composites fabricated by GO-assisted hetero-agglomeration and subsequent SPS process could be a promising material as orthopedic implants.