Synthesis and characterization of biodegradable poly(ϵ‐caprolactone urethane)s. I. Effect of the polyol molecular weight,catalyst, and chain extender on the molecular and physical characteristics

Biodegradable polyurethanes with potential for applications in medical implants were synthesized in bulk with aliphatic hexamethylene diisocyanate, isophorone diisocyanate, poly(?‐caprolactone) diols of various molecular weights, 1,4‐butane diol, 2‐amino‐1‐butanol, thiodiethylene diol, and 2‐mercaptoethyl ether chain extenders. The catalysts used were stannous octoate, dibutyltin dilaurate, ferric acetyl acetonate, magnesium methoxide, zinc octoate, and manganese 2‐ethyl hexanoate. The synthesis reactions were second‐order. All the materials had narrow, unimodal molecular weight distributions and polydispersity indices of 1.5–1.9. The chemical structures of the polyurethanes, as assessed from ¹H NMR and ¹³C NMR spectra, were in good agreement with the monomer stoichiometric ratios. The glass‐transition temperatures of the materials ranged from ?38 to ?57 °C and were higher for polymers based on isophorone diisocyanate and with higher hard‐segment contents. For polyurethanes with the same hard‐segment content, there was no effect of the material molecular weight on the thermal properties. The tensile strengths of the materials were 12–63 MPa, and the tensile moduli were 8–107 MPa. These increased with an increasing hard‐segment content. The least effective catalyst was magnesium methoxide, and the most effective was ferric acetyl acetonate. Stannous octoate and manganese 2‐ethyl hexanoate were less effective than dibutyltin dilaurate and zinc octoate. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 156–170, 2002     

Curcumin‐loaded biodegradable polyurethane scaffolds modified with gelatin using 3D printing technology for cartilage tissue engineering

We described the curcumin‐loaded biodegradable polyurethane (PU) scaffolds modified with gelatin based on three‐dimensional (3D) printing technology for potential application of cartilage regeneration. The printing solution of poly(ε‐caprolactone) (PCL) triol (polyol) and hexamethylene diisocyanate (HMDI) in 2,2,2‐trifluoroethanol was printed through a nozzle in dimethyl sulfoxide phase with or without gelatin. The weight ratio of HMDI against PCL triol was varied as 3, 5, and 7 in order to evaluate its effect on the mechanical properties and biodegradation rate. A higher ratio of HMDI resulted in higher mechanical properties and a lower biodegradation rate. The use of gelatin increased the mechanical properties, biodegradation rate, and curcumin release due to the surface cross‐linking, nanoporous structure, and surface hydrophilicity of the scaffolds. In vitro study revealed that the released curcumin enhanced the proliferation and differentiation of chondrocyte. The 3D‐printed biodegradable PU scaffold modified with gelatin should thus be considered as a potential candidate for cartilage regeneration.     

Vinyl esters: Low cytotoxicity monomers for the fabrication of biocompatible 3D scaffolds by lithography based additive manufacturing

Lithography based additive manufacturing technologies (AMT) like stereolithography or digital light processing have become appealing methods for the fabrication of 3D cellular scaffolds for tissue engineering and regenerative medicine. To circumvent the use of (meth)acrylate‐based photopolymers, that suffer from skin irritation and sometimes cytotoxicity, new monomers based on vinyl esters were prepared. In vitro cytotoxicity studies with osteoblast‐like cells proofed that monomers based on vinyl esters are significantly less cytotoxic than (meth)acrylates. Photoreactivity was followed by photo‐differential scanning calorimetry and the mechanical properties of the photocured materials were screened by nanoindentation. Conversion rates and indentation moduli between those of acrylate and methacrylate references could be observed. Furthermore, osteoblast‐like cells were successfully seeded onto polymer specimens. Finally, we were able to print a 3D test structure out of a vinyl ester‐based formulation by μ‐SLA with a layer thickness of 50 μm. For in vivo testing of vinyl esters these 3D scaffolds were implanted into surgical defects of the distal femoral bone of adult New Zealand white rabbits. The obtained histological results approved the excellent biocompatibility of vinyl esters. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009     

Lysine‐based functional blocked isocyanates for the preparation of polyurethanes provided with pendant side groups

This article describes a methodology to prepare polyurethanes (PUs), decorated with pendant (bio)functional side groups, by polymerizing (bio)functionalized blocked diisocyanates with polyols. Caprolactam blocked lysine diisocyanate methyl ester (BLDI‐OMe) was prepared in high yields, by reacting the methyl ester of lysine with carbonyl biscaprolactam. In the absence of a catalyst, the polymerization of BLDI‐OMe with polycaprolactone and polytetrahydrofuran resulted in strictly linear PUs due to the high selective reactivity of the blocked isocyanates (BIs). Although the ester appeared to be less reactive, we found hydrolyzing conditions for the ester, without affecting the BIs. The free acid groups were converted into a N‐hydroxysuccinimide (NHS) activated ester, which was a versatile intermediate for further functionalization. After having demonstrated that model amines were able to substitute NHS without effecting the BIs groups, the same chemistry was used to couple biotin, giving a biotin functional caprolactam blocked lysine diisocyanate. The polymerization with polyols afforded the corresponding biotin‐functional PUs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2036–2049     

A structural reconsideration: Linear aliphatic or alicyclic hard segments for biodegradable thermoplastic polyurethanes?

Thermoplastic polyurethane elastomers (TPUs) with a biodegradable chain extender and different nonaromatic diisocyanate hard segments were synthesized and tested concerning their thermal, mechanical, and degradation properties and for their processability regarding electrospinning. The design of the TPUs was based on the structural modification of the hard segment using linear aliphatic hexamethylene diisocyanate (HMDI), more rigid alicyclic 4,4′-methylene bis(cyclohexylisocyanate) (H12MDI), 1,3-bis(isocyanatomethyl)cyclohexane (BIMC), or isophorone diisocyanate (IPDI). The soft segment consisted of poly(tetrahydrofuran). Bis(2-hydroxyethyl) terephthalate (BET) was used as chain extender with cleavable ester bonds. Some of the polyurethanes based on alicyclic diisocyanate showed better mechanical performance than the less rigid HMDI-based TPU. The TPU in vitro degradability was tested for 25 days at elevated temperatures in PBS buffer and indicated a bulk erosion process. Electrospinning experiments were conducted and promising results with respect to further applicability of these materials in vascular tissue engineering were obtained. © 2018 The Authors Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2214–2224     

Rubber Seed Oil-Based UV-Curable Polyurethane Acrylate Resins for Digital Light Processing (DLP) 3D Printing

Novel UV-curable polyurethane acrylate (PUA) resins were developed from rubber seed oil (RSO). Firstly, hydroxylated rubber seed oil (HRSO) was prepared via an alcoholysis reaction of RSO with glycerol, and then HRSO was reacted with isophorone diisocyanate (IPDI) and hydroxyethyl acrylate (HEA) to produce the RSO-based PUA (RSO-PUA) oligomer. FT-IR and ¹H NMR spectra collectively revealed that the obtained RSO-PUA was successfully synthesized, and the calculated C=C functionality of oligomer was 2.27 per fatty acid. Subsequently, a series of UV-curable resins were prepared and their ultimate properties, as well as UV-curing kinetics, were investigated. Notably, the UV-cured materials with 40% trimethylolpropane triacrylate (TMPTA) displayed a tensile strength of 11.7 MPa, an adhesion of 2 grade, a pencil hardness of 3H, a flexibility of 2 mm, and a glass transition temperature up to 109.4 °C. Finally, the optimal resin was used for digital light processing (DLP) 3D printing. The critical exposure energy of RSO-PUA (15.20 mJ/cm²) was lower than a commercial resin. In general, this work offered a simple method to prepare woody plant oil-based high-performance PUA resins that could be applied in the 3D printing industry.     

Chemical synthesis of poly‐γ‐glutamic acid by polycondensation of γ‐glutamic acid dimer: Synthesis and reaction of poly‐γ‐glutamic acid methyl ester

α‐Methyl glutamic acid (L ‐L )‐, (L ‐D )‐, (D ‐L )‐, and (D ‐D )‐γ‐dimers were synthesized from L ‐ and D ‐glutamic acids, and the obtained dimers were subjected to polycondensation with 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride and 1‐hydroxybenzotriazole hydrate as condensation reagents. Poly‐γ‐glutamic acid (γ‐PGA) methyl ester with the number‐average molecular weights of 5000∼20,000 were obtained by polycondensation in N,N‐dimethylformamide in 44∼91% yields. The polycondensation of (L ‐L )‐ and (D ‐D )‐dimers afforded the polymers with much larger |[α]_D | compared with the corresponding dimers. The polymer could be transformed into γ‐PGA by alkaline hydrolysis or transesterification into α‐benzyl ester followed by hydrogenation. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 732–741, 2001     

Optimized peptide functionalization of thiol‐acrylate emulsion‐templated porous polymers leads to expansion of human pluripotent stem cells in 3D culture

Highly porous polymers produced by polymerization of the continuous phase of a high internal phase emulsion have been developed as scaffolds for 3D culture of human pluripotent stem cells. These emulsion‐templated polymerized high internal phase emulsion (polyHIPE) materials have an interconnected network of pores that provide support for the cells, while also allowing both cell ingress and nutrient diffusion. Thiol‐acrylate polyHIPE materials were prepared by photopolymerization, which, due to a competing acrylate homopolymerization process, leads to a material with residual surface thiols. These thiols were then used as a handle to allow postpolymerization functionalization with both maleimide and a maleimide‐derivatized cyclo‐RGDfK peptide, via Michael addition under benign conditions. Functionalization was evaluated using an Ellman's colorimetric assay, to monitor the residual thiol concentration, and X‐ray photoelectron spectroscopy. Maleimide was used as a model molecule to optimize conditions prior to peptide‐functionalization. The use of triethylamine as a catalyst and a mixed ethanol‐aqueous solvent system led to optimized reaction between surface‐bound thiols and maleimide. Peptide‐functionalized materials showed improved attachment and infiltration of human pluripotent stem cells over 7 days, demonstrating their promise as a scaffold for 3D stem cell culture and expansion. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1974–1981     

3D printed biodegradable composites: An insight into mechanical properties of PLA/chitosan scaffold

Three-dimensional (3D) printing is a frontier manufacturing approach with great potential to benefit biomedical and patient care sectors. In the last decades, different types of biomedical materials were investigated in purpose of developing medical tools and devices. The present study attempts to assess mechanical performances (namely: tensile, compression, and flexural) of the newly developed chitosan-reinforced poly-lactic-acid (PLA) scaffolds by using fused filament fabrication (FFF) based 3D printing technology. Specifically, the effects of chitosan loading, infill density and annealing temperature on mechanical behavior of PLA composite scaffolds are investigated via design of experiments. Moreover, fracture behavior under various load types is studied with the help of selective electron microscopy. It is found that the strength of the produced composite samples depends significantly on the loading of chitosan and infill density, while annealing temperature does not affect mechanical response. Overall, the developed PLA composite scaffolds are mechanically efficient and they appear suitable for clinical purposes.     

3D printing of conjugated polymers

Three‐dimensional (3D) printing brings exciting prospects to the realm of conjugated polymers (CPs) and organic electronics through vastly enhanced design flexibility, structural complexity, and environmental sustainability. However, the use of 3D printing for CPs is still in its infancy and remains full of challenges. In this review, we highlight recent studies that demonstrate proof‐of‐concept strategies to mitigate some of these problems. Two general additive manufacturing approaches are featured: direct ink writing and vat photopolymerization. We conclude with an outlook for this thriving field of research and draw attention to the new possibilities that 3D printing can bring to CPs. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 1592–1605     

3D打印生物医用材料研究进展

3D打印(亦称增材制造)技术因其独特的材料成型优势,在组织工程、航空航天、汽车制造、以及电子工业等众多领域显示出巨大的应用潜力。然而,在实际生物医学应用中,3D打印生物器件和组织器官除了要求具有复杂的结构和优异的生物学性能外,其打印结构的表面性质也需满足某些特定的要求,如3D打印组织骨架和器官必须具有生物相容性、抗菌性及细胞粘附性等。因此,将3D打印与传统表面修饰技术相结合,在不改变材料三维结构的基础上调控其表面生物化学性质,从而赋予3D打印生物骨架器官多功能化,可实现更为广泛的应用。本文以3D打印生物骨架及器官的表面修饰为主要内容对就近年来3D打印生物医用材料的最新研究进展进行了综述。     

Preparation and characterization of waterborne poly(urethane urea) with well‐defined hard segments

A series of polyester‐based poly(urethane urea) (PUU) aqueous dispersions with well‐defined hard segments were prepared from polyester polyol, 4,4′‐diphenylmethane diisocyanate, dimethylolpropionic acid, 1,4‐butanediol, isophorone diisocyanate, and ethylenediamine. These anionic‐type aqueous dispersions had good dispersity in water and were stable at the ambient temperature for more than 1 year. For these aqueous dispersions, the particle size decreased as the hard‐segment content increased, and the polydispersity index was very narrow (<1.10). Films prepared with the PUU aqueous dispersions exhibited excellent waterproof performance: the amount of water absorption was as low as 5.0 wt %, and the contact angle of water on the surface of this kind of film was as high as 103° (this led to a hydrophobic surface). The water‐resistant property of these waterborne PUU films could be well correlated with some crystallites and ordered structures of the well‐defined hard segments formed by hydrogen bonding between the urethane/urethane groups and urethane/ester groups, as well as the degree of microphase separation between the hard and soft segments in the PUU systems. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2606–2614, 2005     

Enhanced Cell Penetration and Pluripotency Maintenance of hiPSCs in 3D Natural Chitosan Scaffolds

Human-induced pluripotent stem cells (hiPSCs) cultured in 3D matrices hold great promise in disease modeling, drug discovery, and tissue regeneration. Uniform cell distribution in a 3D structure is critical to the growth and function of hiPSCs, yet cell seeding in 3D matrices often remains superficial, leading to limited cell proliferation and compromised pluripotency. Here, an approach to improve cell penetration depth of hiPSCs in 3D scaffolds modified with hiPSCs conditioned medium (CM) is reported. It is shown that extracellular matrix components are successfully deposited onto the scaffold wall surface after CM treatment and promoted homogeneous cell adhesion during initial seeding. Compared to plain, unmodified scaffolds, the CM treated scaffold improves spatial cell distribution uniformity and upregulates pluripotency markers. Notably, the expression of 29 genes associated with 11 signaling pathways participated in the pluripotency maintenance of hiPSCs exhibits >2-fold change in hiPSCs grown in the CM treated scaffolds than 2D counterparts, demonstrating that CM treated scaffolds can support a more primitive and undifferentiated phenotype of hiPSCs. This study introduces a simple and effective method to enhance cell penetration and maintain cell pluripotency in 3D matrices.     

Hydrolyzable poly(ester-urethane) networks from L-lysine diisocyanate and D,L-lactide/ϵ-caprolactone homo- and copolyester triols

Bioabsorbable poly(ester-urethane) networks were synthesized from ethyl 2,6-diisocyanatohexanoate (L -lysine diisocyanate) (LDI) and a series of polyester triols. LDI was synthesized by refluxing L-lysine monohydrochloride with ethanol to form the ester, which was subsequently refluxed with 1,1,1,3,3,3-hexamethyldisilazane to yield a silazane-protected intermediate. This product was then phosgenated using triphosgene. Polyester triols were synthesized from D,L-lactide, ?-caprolactone, or comonomer mixtures thereof, using glycerol as initiator and stannous octoate as catalyst. Polyurethane networks were cured using [NCO]/[OH] = 1.05 and stannous octoate (0.05 wt %) for 24 h at room temperature and pressure and 24 h at 50°C and 0.1 mm Hg. LDI-based polyurethane networks were totally amorphous and possessed very low sol contents. Networks based on poly (D,L-lactide) triols were rigid (T_g ∽ 60°C) with ultimate tensile strengths of ～ 40–70 MPa, tensile moduli of ～ 1.2–2.0 GPa, and ultimate elongations of ～ 4–10%. Networks based on ?-caprolactone triols were low-modulus elastomers with tensile strengths and moduli of ～ 1–4 MPa and ～ 3–6 GPa, respectively, and ultimate elongations of ～ 50–300%. Networks based on copolymers displayed physical properties consistent with monomer composition and were tougher than the networks based on the homopolymers. Tensile strengths for the copolymers were ～ 3–25 MPa with ultimate elongations up to 600%. Hydrolytic degradation under simulated physiological conditions showed that D ,L -lactide homopolymer networks were the most resistant to degradation, undergoing virtually no change in mass or physical properties for 60 days. ?-Caprolactone-based networks were resistant to degradation for 40 days, and high-lactide copolymer-based networks suffered substantial losses in physical properties after only 3 days. © 1994 John Wiley & Sons, Inc.     

Incorporation of nanohydroxyapatite and vitamin D3 into electrospun PCL/Gelatin scaffolds: The influence on the physical and chemical properties and cell behavior for bone tissue engineering

Scaffold, an essential element of tissue engineering, should provide proper physical and chemical properties and evolve suitable cell behavior for tissue regeneration. Polycaprolactone/Gelatin (PCL/Gel)‐based nanocomposite scaffolds containing hydroxyapatite nanoparticles (nHA) and vitamin D3 (Vit D3) were fabricated using the electrospinning method. Structural and mechanical properties of the scaffold were determined by scanning electron microscopy (SEM) and tensile measurement. In this study, smooth and bead‐free morphology with a uniform fiber diameter and optimal porosity level with appropriate pore size was observed for PCL/Gel/nHA nanocomposite scaffold. The results indicated that adding nHA to PCL/Gel caused an increase of the mechanical properties of scaffold. In addition, chemical interactions between PCL, gelatin, and nHA molecules were shown with XRD and FT‐IR in the composite scaffolds. MG‐63 cell line has been cultured on the fabricated composite scaffolds; the results of viability and adhesion of cells on the scaffolds have been confirmed using MTT and SEM analysis methods. Here in this study, the culture of the osteoblast cells on the scaffolds showed that the addition of Vit D3 to PCL/Gel/nHA scaffold caused further attachment and proliferation of the cells. Moreover, DAPI staining results showed that the presence and viability of the cells were greater in PCL/Gel/nHA/Vit D3 scaffold than in PCL/Gel/nHA and PCL/Gel scaffolds. The results also approved increasing cell proliferation and alkaline phosphatase (ALP) activity for MG‐63 cells cultured on PCL/Gel/nHA/Vit D3 scaffold. The results indicated superior properties of hydroxyapatite nanoparticles and vitamin D3 incorporated in PCL/Gel scaffold for use in bone tissue engineering.     

UV-curable poly(ethylene glycol)–based polyurethane acrylate hydrogel

Poly(ethylene glycol) (PEG) with molecular weight (M_n) of 1000, 2000, 3000, and 4000 g/mol, four types of diisocyanate [hexamethylene diisocyanate (HDI), 4,4′-dicyclohexylmethane diisocyanate (H₁₂MDI), isophorone diisocyanate (IPDI), and toluene diisocyanate (TDI)], two types of comonomers [acrylamide (AAm) and acrylic acid (AAc)] that comprised up to 60% of the total solid were used to prepare UV-curable PEG–based polyurethane (PU) acrylate hydrogel. The gels were evaluated in terms of mechanical properties, water content as a function of immersion time and pH, and X-ray diffraction profiles of dry and swollen films. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2703–2709, 1999     

Biodegradable photocrosslinkable poly(depsipeptide‐co‐ε‐caprolactone) for tissue engineering: Synthesis,characterization, and In vitro evaluation

Stereolithography has become increasingly popular in scaffold fabrication due to automation and well‐controlled geometry complexity, and consequently, there is a great need for new suitable biodegradable photocrosslinkable polymers. In this study, a new type of photocrosslinkable poly(ester amide) was synthesized based on ε‐caprolactone and l ‐alanine‐derived depsipeptide and was applied to fabrication of three‐dimensional (3D) scaffolds by stereolithography. ¹H nuclear magnetic resonance and Fourier transform infra‐red analysis confirmed the formation of new bonds during the polymer synthesis. Incorporation of depsipeptide increased the glass transition temperature and hydrophilicity of the polymer and accelerated hydrolytic degradation compared with the poly(ε‐caprolactone) homopolymer. The compressive strength of the 3D scaffolds increased with the increasing depsipeptide content. This work demonstrated that incorporation of depsipeptide into photocrosslinkable polyesters resulted in excellent cytocompatibility and tunable degradation rates and mechanical properties and thus expanded the repertoire of biomaterials suitable for 3D photofabrication of high‐resolution tissue engineering scaffolds. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3307–3315     

3D Printed Polycaprolactone Carbon Nanotube Composite Scaffolds for Cardiac Tissue Engineering

Fabrication of tissue engineering scaffolds with the use of novel 3D printing has gained lot of attention, however systematic investigation of biomaterials for 3D printing have not been widely explored. In this report, well‐defined structures of polycaprolactone (PCL) and PCL‐ carbon nanotube (PCL‐CNT) composite scaffolds have been designed and fabricated using a 3D printer. Conditions for 3D printing has been optimized while the effects of varying CNT percentages with PCL matrix on the thermal, mechanical and biological properties of the printed scaffolds are studied. Raman spectroscopy is used to characterise the functionalized CNTs and its interactions with PCL matrix. Mechanical properties of the composites are characterised using nanoindentation. Maximum peak load, elastic modulus and hardness increases with increasing CNT content. Differential scanning calorimetry (DSC) studies reveal the thermal and crystalline behaviour of PCL and its CNT composites. Biodegradation studies are performed in Pseudomonas Lipase enzymatic media, showing its specificity and effect on degradation rate. Cell imaging and viability studies of H9c2 cells from rat origin on the scaffolds are performed using fluorescence imaging and MTT assay, respectively. PCL and its CNT composites are able to show cell proliferation and have the potential to be used in cardiac tissue engineering.

     

Fabrication of 3D electrospun structures from poly(lactide‐co‐glycolide acid)–nano‐hydroxyapatite composites

The fabrication of three‐dimensional (3D) electrospun composite scaffolds was presented in this study. Layers of electrospun meshes made from composites of poly(lactide‐co‐glycolide acid) (PLGA) and hydroxyapatite (HA) were stacked and sintered using pressurized gas. Three HA concentrations of 5, 10, and 20 wt % were tested, and the addition of the HA nanoparticles decreased the tensile mechanical properties of the meshes with 20 wt % HA. However, after the gas absorption process, the fibers within the mesh sintered, which improved the mechanical properties more than twofold. The fabrication of 3D, porous, electrospun scaffolds was also demonstrated. The resulting 3D scaffolds had open porosity of up to 70% and modulus of ～20 MPa. This technique improves on the current electrospinning technology by overcoming the challenges of depositing a thick, 3D structure. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

3D printed polylactic acid nanocomposite scaffolds for tissue engineering applications

In this study, biodegradable polylactic acid (PLA) and PLA nanocomposite scaffolds reinforced with magnetic and conductive fillers, were processed via fused filament fabrication additive manufacturing and their bioactivity and biodegradation characteristics were examined. Porous 3D architectures with 50% bulk porosity were 3D printed, and their physicochemical properties were evaluated. Thermal analysis confirmed the presence of ~18 wt% of carbon nanostructures (CNF and GNP; nowonwards CNF) and ~37 wt% of magnetic iron oxide (Fe₂O₃) particles in the filaments. The in vitro degradation tests of scaffolds showed porous and fractured struts after 2 and 4 weeks of immersion in DMEM respectively, although a negligible weight loss is observed. Greater extent of degradation is observed in PLA with magnetic fillers followed by PLA with conductive fillers and neat PLA. In vitro bioactivity study of scaffolds indicate enhancement from ~2.9% (PLA) to ~5.32% (PLA/CNF) and ~ 3.12% (PLA/Fe₂O₃). Stiffness calculated from the compression tests showed decrease from ~680 MPa (PLA) to 533 MPa and 425 MPa for PLA/CNF and PLA/Fe₂O₃ respectively. Enhanced bioactivity and faster biodegradation response of PLA nanocomposites with conductive fillers make them a potential candidate for tissue engineering applications such as scaffold bone replacement and regeneration.