Supramolecular Nanostructures for the Delivery of Peptides in Cancer Therapy.

Supramolecular nanostructured based delivery systems are emerging as a meaningful approach in the treatment of cancer, offering controlled drug release and improved therapeutic efficacy. The self-assembled structures can be small molecules, polymers, peptides, or proteins, which can be used and functionalized to achieve tailored release and target specific cells, tissues, or organs. These structures can improve the solubility and stability of drugs having low aqueous solubility by encapsulating and protecting them from degradation. Alongside, peptides as natural biomolecules have gained increasing attention as potential candidates in cancer treatment because of their biocompatibility, low cytotoxicity, and high specificity toward tumor cells. The amino acid sequences in peptide molecules are tunable, efficiently controlling the morphology of peptide-based self-assembled nanosystems and offering flexibility to form supramolecular nanostructures (SNs). It is evident from the current literature that the supramolecular nanostructures based delivery of peptide for cancer treatment hold great promise for future cancer therapy, offering potential strategies for personalized medicine with improved patient outcomes. SIGNIFICANCE STATEMENT: This review focuses on fundamentals and various drug delivery mechanisms based on SNs. Different SN approaches and recent literature reviews on peptide delivery are also presented to the readers.

A Lipophilic Salt Form to Enhance the Lipid Solubility and Certain Biopharmaceutical Properties of Lapatinib.

Lapatinib (LTP) commercially available as lapatinib ditosylate (LTP-DTS) salt is the only drug approved for the treatment of HER-positive metastatic breast cancer. A low and pH-dependent solubility results in poor and variable oral bioavailability, thus driving significant interest in molecular modification and formulation strategies of the drug. Furthermore, due to very high crystallinity, LTP and LTP-DTS have low solubility in lipid excipients, making it difficult to be delivered by lipid-based carrier systems. Thus, the present work reports a new salt form of LTP with a docusate counterion to enhance the pharmaceutical properties of the drug (LTP-DOC). NMR spectra showed a downfield shift of the methylene singlet proton from 3.83 and 4.41 ppm, indicating a lowering of electron density on the adjacent nitrogen atom and confirming the formation of amine-sulfonyl salt through the specified basic nitrogen center located adjacent to the furan ring. PXRD diffractograms of LTP-DOC indicated a reduced crystallinity of the prepared salt. The dissolution, equilibrium solubility, lipid excipient solubility, partitioning coefficient, distribution coefficient, tabletability, and in vitro cytotoxicity of the lipophilic salt of LTP were investigated. The equilibrium solubility data showed that LTP-DOC possesses a pH-independent solubility profile in the pH range of 3.5 to 7.4 with a 3.14 times higher permeability coefficient than commercial ditosylate salt. Furthermore, the prepared LTP-DOC salts showed twice higher log P than the free base and 8 times higher than LTP-DTS. The prepared LTP-DOC was found to have 4- to 9-fold higher solubility in lipid excipients like Capmul MCM C8 and Maisine CC compared to the ditosylate salt. The LTP-DOC salt was tabletable and showed approximately 1.2 times lower dissolution than commercial ditosylate salt, indicating extended-release behavior. A cytotoxicity study of LTP-DOC salt showed an approximately 2.5 times lower IC50 value than the LTP-free base and 1.7 times lower than commercial ditosylate salt with an approximately 3 times higher selectivity index. The investigations strongly indicate a high translational potential of the prepared salt form in maintaining solubility-lipophilicity interplay, enhancing the drug's bioavailability, and developing lipidic formulations.

Probing the Influence of Hybrid Thread Design on Biomechanical Response of Dental Implants: Finite Element Study and Experimental Validation.

This study aimed to perform quantitative biomechanical analysis for probing the effect of varying thread shapes in an implant for improved primary stability in prosthodontics surgery. Dental implants were designed with square (SQR), buttress (BUT), and triangular (TRI) thread shapes or their combinations. Cone-beam computed tomography images of mandible molar zones in human subjects belonging to three age groups were used for virtual implantation of the designed implants, to quantify patient-specific peri-implant bone microstrain, using finite element analyses. The in silico analyses were carried out considering frictional contact to simulate immediate loading with a static masticatory force of 200 N. To validate computational biomechanics results, compression tests were performed on three-dimensional printed implants having the investigated thread architectures. Bone/implant contact areas were also quantitatively assessed. It was observed that, bone/implant contact was maximum for SQR implants followed by BUT and TRI implants. For all the cases, peak microstrain was recorded in the cervical cortical bone. The combination of different thread shapes in the middle or in the apical part (or both) was demonstrated to improve peri-implant microstrain, particularly for BUT and TRI. Considering 1500-2000 microstrain generates in the peri-implant bone during regular physiological functioning, BUT-SQR, BUT-TRI-SQR, TRI-SQR-BUT, SQR, and SQR-BUT-TRI design concepts were suitable for younger; BUT-TRI-SQR, BUT-SQR-TRI, TRI-SQR-BUT, SQR-BUT, SQR-TRI for middle-aged, and BUT-TRI-SQR, BUT-SQR-TRI, TRI-BUT-SQR, SQR, and SQR-TRI for the older group of human patients.

Radiographic analysis of Müller-Weiss disease.

BACKGROUND: The only classification of Müller-Weiss disease (MWD) is based primarily on Méary's talo-first metatarsal angle. It describes increasing sag of the medial longitudinal arch with greater degrees of compression and fragmentation of the navicular. Purportedly, the talar head pushes the subtalar joint into varus and drives the medial pole of the navicular medially, as it protrudes inferiorly and laterally. Its authors stipulated heel varus as a pre-requisite, coining the term 'paradoxical pes planus varus' to define heel varus and flatfoot as hallmark deformities of the condition. METHODS: We measured Méary's and Kite's talocalcaneal angles, heel offset, anteroposterior thickness of the navicular at each naviculocuneiform (NC) joint, medial extrusion of the navicular and calculated percentage compression at each NC joint in 68 consecutive feet presenting with MWD. Morphology and activity at the various peri-navicular joints were studied using SPECT-CT in 45 feet. RESULTS: Inverse relationships between Méary's angle and degree of navicular compression reach statistical significance at NC2 but not at NC3. Strong correlation exists between medial extrusion and percentage compression at NC2 and NC3. Medial extrusion is significantly greater on the affected side in unilateral cases and on the more compressed side in bilateral cases. Significant inverse relationships exist between Kite's angle and percentage compression at both NC2 and NC3 and degree of medial extrusion of the navicular. No correlation was detected between Kite's angle and either heel offset or Méary's angle. Varus heel offset was present in only 33% of cases. The combination of heel varus and negative Méary's angle was present in just 26% of cases, the commonest combination being heel valgus with sagging at 56%. CONCLUSION: Our findings confirm part of Maceira's hypothesized pathomechanism of MWD. Reductions in Kite's talocalcaneal angle confirm that lateral and inferior protrusion of the talar head causes increasing compression and medial extrusion of the navicular. However, such shift of the talar head does not always lead to heel varus. As such, we caution against universal advocacy of lateral displacement calcaneal osteotomy, as the heel is not always in varus in MWD.

Nanoparticulate formulations of radiopharmaceuticals: Strategy to improve targeting and biodistribution properties.

Application of nanotechnology principles in drug delivery has created opportunities for treatment of several diseases. Nanotechnology offers the advantage of overcoming the adverse biopharmaceutics or pharmacokinetic properties of drug molecules, to be determined by the transport properties of the particles themselves. Through the manipulation of size, shape, charge, and type of nanoparticle delivery system, variety of distribution profiles may be obtained. However, there still exists greater need to derive and standardize definitive structure property relationships for the distribution profiles of the delivery system. When applied to radiopharmaceuticals, the delivery systems assume greater significance. For the safety and efficacy of both diagnostics and therapeutic radiopharmaceuticals, selective localization in target tissue is even more important. At the same time, the synthesis and fabrication reactions of radiolabelled nanoparticles need to be completed in much shorter time. Moreover, the extensive understanding of the several interesting optical and magnetic properties of materials in nanoscale provides for achieving multiple objectives in nuclear medicine. This review discusses the various nanoparticle systems, which are applied for radionuclides and analyses the important bottlenecks that are required to be overcome for their more widespread clinical adaptation.

Convolutional networks for fast, energy-efficient neuromorphic computing.

Deep networks are now able to achieve human-level performance on a broad spectrum of recognition tasks. Independently, neuromorphic computing has now demonstrated unprecedented energy-efficiency through a new chip architecture based on spiking neurons, low precision synapses, and a scalable communication network. Here, we demonstrate that neuromorphic computing, despite its novel architectural primitives, can implement deep convolution networks that (i) approach state-of-the-art classification accuracy across eight standard datasets encompassing vision and speech, (ii) perform inference while preserving the hardware's underlying energy-efficiency and high throughput, running on the aforementioned datasets at between 1,200 and 2,600 frames/s and using between 25 and 275 mW (effectively >6,000 frames/s per Watt), and (iii) can be specified and trained using backpropagation with the same ease-of-use as contemporary deep learning. This approach allows the algorithmic power of deep learning to be merged with the efficiency of neuromorphic processors, bringing the promise of embedded, intelligent, brain-inspired computing one step closer.

Thermally-controlled extrusion-based bioprinting of collagen.

Thermally-crosslinked hydrogels in bioprinting have gained increasing attention due to their ability to undergo tunable crosslinking by modulating the temperature and time of crosslinking. In this paper, we present a new bioink composed of collagen type-I and Pluronic® F-127 hydrogels, which was bioprinted using a thermally-controlled bioprinting unit. Bioprintability and rheology of the composite bioink was studied in a thorough manner in order to determine the optimal bioprinting time and extrusion profile of the bioink for fabrication of three-dimensional (3D) constructs, respectively. It was observed that collagen fibers aligned themselves along the directions of the printed filaments after bioprinting based on the results on an anisotropy study. Furthermore, rat bone marrow-derived stem cells (rBMSCs) were bioprinted in order to determine the effect of thermally-controlled extrusion process. In vitro viability and proliferation study revealed that rBMSCs were able to maintain their viability after extrusion and attached to collagen fibers, spread and proliferated within the constructs up to seven days of culture.

Challenges in Bio-fabrication of Organoid Cultures.

Three-dimensional (3D) organoids have shown advantages in cell culture over traditional two-dimensional (2D) culture, and have great potential in various applications of tissue engineering. However, there are limitations in current organoid fabrication technologies, such as uncontrolled size, poor reproductively, and inadequate complexity of organoids. In this chapter, we present the existing techniques and discuss the major challenges for 3D organoid biofabrication. Future perspectives on organoid bioprinting are also discussed, where bioprinting technologies are expected to make a major contribution in organoid fabrication, such as realizing mass production and constructing complex heterotypic tissues, and thus further advance the translational application of organoids in tissue engineering and regenerative medicine as well drug testing and pharmaceutics.

Repositing honey incorporated electrospun nanofiber membranes to provide anti-oxidant, anti-bacterial and anti-inflammatory microenvironment for wound regeneration.

Topical application of honey for tissue regeneration, has recently regained attention in clinical practice with controlled studies affirming its efficacy and indicating its role in regeneration over repair. Parallely, to overcome difficulties of applying raw honey, several product development studies like nanofibrous matrices have been reported. However, one approach concentrated on achieving highest possible honey loading in the nanofiber membranes while other studies have found that only specific honey dilutions result in differential cellular responses on wound healing and re-epithelization. From these results, it can be suggested that high honey loading provides optimum external microenvironment, low-loaded membranes could provide a more conducive internal microenvironment for tissue regeneration. With this hypothesis, this paper sought to evaluate ability of low-honey loaded nanofibers to modulate the anti-oxidant, anti-biofilm and anti-inflammatory properties which are important to be maintained in wound micro-environment. A loading-dependent reduction of biofilm formation and anti-oxidant activity was noted in different concentration ranges investigated. After scratch assay, a certain honey loading (0.5%) afforded the maximum re-epithelization. Since there is lack of methods to determine anti-inflammatory properties of nanofiber membranes during epithelial healing process, we performed anti-inflammatory assessment of nano-fibers by evaluating the expressions of pro-inflammatory markers-Cycloxygenase-2 (COX-2) and Interleukin-6 (IL-6) and to confirm the optimized concentration. Considering the role of COX-2 and IL-6, the novel methodology used in this study can also be developed as an assay for anti-inflammatory matrices for wound healing.

Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives.

: Three-dimensional (3D) bioprinting is a revolutionary technology in building living tissues and organs with precise anatomic control and cellular composition. Despite the great progress in bioprinting research, there has yet to be any clinical translation due to current limitations in building human-scale constructs, which are vascularized and readily implantable. In this article, we review the current limitations and challenges in 3D bioprinting, including in situ techniques, which are one of several clinical translational models to facilitate the application of this technology from bench to bedside. A detailed discussion is made on the technical barriers in the fabrication of scalable constructs that are vascularized, autologous, functional, implantable, cost-effective, and ethically feasible. Clinical considerations for implantable bioprinted tissues are further expounded toward the correction of end-stage organ dysfunction and composite tissue deficits.

Bone tissue bioprinting for craniofacial reconstruction.

Craniofacial (CF) tissue is an architecturally complex tissue consisting of both bone and soft tissues with significant patient specific variations. Conditions of congenital abnormalities, tumor resection surgeries, and traumatic injuries of the CF skeleton can result in major deficits of bone tissue. Despite advances in surgical reconstruction techniques, management of CF osseous deficits remains a challenge. Due its inherent versatility, bioprinting offers a promising solution to address these issues. In this review, we present and analyze the current state of bioprinting of bone tissue and highlight how these techniques may be adapted to serve regenerative therapies for CF applications. Biotechnol. Bioeng. 2017;114: 2424-2431. © 2017 Wiley Periodicals, Inc.

Effect of probiotics supplementation on liver stiffness and steatosis in patients with NAFLD.

Background and Aim: To compare the effects of probiotics on liver stiffness and steatosis in obese and non-obese patients with nonalcoholic fatty liver disease (NAFLD),the pragmatic clinical trial included 50 obese body mass index (BMI) ≥25 kg/m2 and 50 non-obese NAFLD BMI <25 kg/m2 age and sex-matched patients. Materials and Methods: Fibroscan with controlled attenuated parameter (CAP) was done at day 0 and at the end of 6 months. Probiotics supplementation was provided for both groups for 6 months along with lifestyle modifications. Results: At inclusion, both groups had comparable characteristics except BMI, metabolic syndrome and waist circumference (WC). Beneficial changes occurred in BMI (p=0.024), WC (p=0.045), ALT (p=0.024), total cholesterol (p=0.016), LDL (p=0.025) and triglyceride (p=0.021) of obese group, systolic blood pressure (p=0.003) and LDL level (p=0.018) in non-obese group. No significant change was observed in liver enzymes and glycemic profiles. Significant improvement in CAP was observed in both groups. But after adjusting for changes in BMI and WC, the change in CAP among non-obese participants were significantly higher compared to obese, mean change of 19.33±48.87 and 16.02±51.58 dB/m in non-obese and obese patients, respectively; p=0.044). Conclusion: Probiotics improve CAP/ steatosis in both obese and non-obese NAFLD patients and improvement was higher in non-obese, irrespective of BMI change.

Supramolecular J- and H-aggregation of Napthalimide-conjugated Dipeptide in Mixed-solvent Systems and Its Application in Cell Imaging.

In this work, a core substituted NMI-conjugated dipeptide (4MNLV) was extensively studied in mixed solvent systems to explore the polarity effect on the self-assembly pattern and their photophysical property. 4MNLV adopted a J- or H- type aggregation pattern depending upon the polarity index of the solvent system chosen. The self-assembly process was achieved through the anti-solvent effect. UV-vis study suggested that if the stock solution of 4MNLV was diluted with a relatively more polar solvent (compared to the stock solvent), then the system acquired J- type of aggregation pattern by showing a red-shift in their absorption maxima (λmax). Conversely, when the stock was diluted by a relatively less polar solvent, H-type of aggregation was observed where blue shift of λmax was noticed. The emission spectra and the lifetime of the self-assembled materials were also influenced by the chosen solvent system. The chirotopic behaviour of these self-assembled materials was studied through CD spectroscopy. Morphological study indicated the formation of helical nanofibrillar structures. The bright green fluorescence of these highly biocompatible naphthalimide-peptide conjugate was used for cell imaging application, indicating its futuristic scope.

Spatiotemporally Controlled Release of Etamsylate from Bioinspired Peptide-Functionalized Nanoparticles Arrests Bleeding Rapidly and Improves Clot Stability in a Rabbit Internal Hemorrhage Model.

Achieving rapid clotting and clot stability are important unmet goals of clinical management of noncompressible hemorrhage. This study reports the development of a spatiotemporally controlled release system of an antihemorrhagic drug, etamsylate, in the management of internal hemorrhage. Gly-Arg-Gly-Asp-Ser (GRGDS) peptide-functionalized chitosan nanoparticles, with high affinity to bind with the GPIIa/IIIb receptor of activated platelets, were loaded with the drug etamsylate (etamsylate-loaded GRGDS peptide-functionalized chitosan nanoparticles; EGCSNP). Peptide conjugation was confirmed by LCMS, and the delivery system was characterized by DLS, SEM, XRD, and FTIR. In vitro study exhibited 90% drug release till 48 h fitting into the Weibull model. Plasma recalcification time and prothrombin time tests of GRGDS-functionalized nanoparticles proved that clot formation was 1.5 times faster than nonfunctionalized chitosan nanoparticles. The whole blood clotting time was increased by 2.5 times over clot formed under nonfunctionalized chitosan nanoparticles. Furthermore, the application of rheometric analysis revealed a 1.2 times stiffer clot over chitosan nanoparticles. In an in vivo liver laceration rabbit model, EGCSNP spatially localized at the internal injury site within 5 min of intravenous administration, and no rebleeding was recorded up to 3 h. The animals survived for 3 weeks after the injury, indicating the strong potential of the system for the management of noncompressible hemorrhage.

Experimental and simulation investigation of surgical needle insertion into soft tissue mimic biomaterial for minimally invasive surgery (MIS).

The surgical needle insertion process is widely applied in medical interference. During the insertion process, the inhomogeneity and denseness of the soft tissues make it tough to detect the essential tissue damage, a rupture occurs that contains huge forces and material deformations. This study is very important, as all the above-mentioned factors are very significant for modern invasive surgery so that the success rate of the surgery can increase and the patient recovers smoothly. This investigation intends to perform minimally invasive surgical (MIS) procedures and reduce the living tissue damage while performing the biopsy, PCNL, etc. A fracture mechanics method was analyzed to create a needle insertion model which can estimate the needle insertion force during inset in tissue-like PVA gel. The force model was calculated by needle insertion experimentally, and also estimated the needle tip geometry, and diameter influences the fracture toughness. Validate exp. results with simulation results and other papers. It is observed that needle diameter has a significant effect on fracture toughness, whereas the insertion velocity has a slight impact on the fracture toughness. During the rotational needle insertion process, the winds-up of the gel occurs and the diameter of the hole was increasing with increased rpm. Maximum insertion force was noticed in the 27 G needle at 5 mm/s. The interaction function will be less at the maximum fracture development region.

Simulation and experimental investigation of the surgical needle deflection model during the rotational and steady insertion process.

Needle insertion is executed in numerous medical and brachytherapy events. Exact needle insertion into inhomogeneous soft biological tissue is of useful importance due to its significance in clinical diagnosis (especially percutaneous) and treatments. The surgical needles used in such processes can deflect during the percutaneous process. Needle deflecting which affects needle - soft tissue interface and needle controllability have a crucial role in establishment precision. In this paper, we have analyzed a mechanics-based model both rotational and non-rotational needle insertion, and studied the deflection phenomenon in both insertion cases, we validated it with a real-time nonlinear Dassault Systèmes® ABAQUS simulation model. For definite contact force, the maximum the contact stiffness was, the minimum it inserted, the cohesive surface model was used to investigate the needle insertion analysis, where the fracture point was defined by a failure strain and with the help of the in, the fully failed components would be removed. Using living tissue comparable PVA gel materials, the needle insertion force model is developed from insertion experimentations with the help of two different processes (rotational and non-rotational needle insertion). In a rotational needle, deflection is less than in a non-rotational needle. The preliminary insertion was observed in the rotational needle at 1.261 mm (experiment), and 1.538 mm (simulation), and for non-rotational needle insertion, the initial insertion was noticed at 1.756 mm (experiment) and 1.982 mm (simulation). The main aim of this study is to navigate the surgical needle in an accurate way to reduce the erroneousness for a clinical diagnosis like anesthesia, brachytherapy, biopsy, and modern microsurgery operation.

Ethical challenges with 3D bioprinted tissues and organs.

3D Bioprinting is fast advancing to offer capabilities to process living cells into geometrically and functionally complex tissue and organ substitutes. As bioprinted constructs are making their way into clinic, the bioprinting community needs to consider the responsible innovation and translation of the bioprinted tissues and organs.

Vitamin D3-incorporated chitosan/collagen/fibrinogen scaffolds promote angiogenesis and endothelial transition via HIF-1/IGF-1/VEGF pathways in dental pulp stem cells.

Effective vascularization during wound healing remains a critical challenge in the regeneration of skin tissue. On the other hand, mesenchymal stem cell (MSC) to endothelial phenotype transition (MEnDoT) is a potential phenomenon grossly underexplored in vascularized skin tissue engineering. Vitamin D3 has a proven role in promoting MEnDoT. Hence, a D3-incorporated scaffold made with biocompatible materials such as chitosan, collagen and fibrinogen should be able to promote endothelial lineage transition in vitro for tissue engineering purposes. In this study, we developed vitamin D3 incorporated chitosan-collagen-fibrinogen (CCF-D3) scaffolds physically crosslinked under UV and conducted thorough physicochemical and biological assays on it compared to a control scaffold without vitamin D3. Our study for the first time reports the potential vascularization property of the CCF-D3 scaffold by inducing the transitions of dental pulp MSC to endothelial lineage via the HIF-1/IGF-1/VEGF pathways. MSC seeded on UV-exposed CCF-D3 scaffolds had higher cell viability and transitioned towards endothelial lineage was observed by elevated proliferative and endothelial-specific gene expressions and flow cytometric analysis of SCA-1+ antibody. The difference in VEGF-A and α-SMA expressions was also observed in the D3-CCF scaffold compared to the scaffolds without D3.

3D Printing of Ti-6Al-4V-Based Porous-Channel Dental Implants: Computational, Biomechanical, and Cytocompatibility Analyses.

Objective: Loosening of dental implants due to resorption of the surrounding bone is one of the challenging clinical complications in prosthetic dentistry. Generally, stiffness mismatch between an implant and its surrounding bone is one of the major factors. In order to prevent such clinical consequences, it is essential to develop implants with customized stiffness. The present study investigates the computational and experimental biomechanical responses together with cytocompatibility studies of three-dimensional (3D)-printed Ti-6Al-4V-based porous dental implants with varied stiffness properties. Methods: Additive manufacturing (direct metal laser sintering, DMLS) was utilized to create Ti-6Al-4V implants having distinct porosities and pore sizes (650 and 1000 µm), along with a nonporous (solid) implant. To validate the compression testing of the constructed implants and to probe their biomechanical response, finite element models were employed. The cytocompatibility of the implants was assessed using MG-63 cells, in vitro. Results: Both X-ray microcomputed tomography (µ-CT) and scanning electron microscopy (SEM) studies illustrated the ability of DMLS to produce implants with the designed porosities. Biomechanical analysis results revealed that the porous implants had less stiffness and were suitable for providing the appropriate peri-implant bone strain. Although all of the manufactured implants demonstrated cell adhesion and proliferation, the porous implants in particular supported better bone cell growth and extracellular matrix deposition. Conclusions: 3D-printed porous implants showed tunable stiffness properties with clinical translational potential.

Patient-specific femoral implant design using metamaterials for improving load transfer at proximal-lateral region of the femur.

Loading configuration of hip joint creates resultant bending effect on femoral implants. So, the lateral side of femoral implant which is under tension retracts from peri­implant bone due to positive Poisson's ratio. This retraction of implant leads to load shielding and gap opening in proximal-lateral region, thereby allowing entry of wear particle to implant-bone interface. Retraction of femoral implant can be avoided by introducing auxetic metamaterial to the retracting side. This allows the implant to push peri­implant bone under tensile condition by virtue of their auxetic (negative Poisson's ratio) nature. To develop such implants, a patient-specific conventional solid implant was first designed based on computed-tomography scan of a patient's femur. Two types of metamaterials (2D: type-1) and (3D: type-2) were employed to design femoral meta-implants. Type-1 and type-2 meta-implants were fabricated using metallic 3D printing method and mechanical compression testing was conducted. Three finite element (FE) models of the femur implanted with solid implant, type-1 meta-implant and type-2 meta-implant were developed and analysed under compression loading. Significant correlation (R2 = 0.9821 and R2 = 0.9977) was found between the experimental and FE predicted strains of the two meta-implants. In proximal-lateral region of the femur, an increase of 7.1% and 44.1% von-Mises strain was observed when implanted with type-1 and type-2 meta-implant over the solid implant. In this region, bone remodelling analysis revealed 2.5% bone resorption in case of solid implant. While bone apposition of 0.5% and 7.7% was observed in case of type-1 and type-2 meta-implants, respectively. The results of this study indicates that concept of introduction of metamaterial to the lateral side of femoral implant can prove to provide higher osseointegration-friendly environment in the proximal-lateral region of femur.