Harpreet Singh Pawar

On-Demand Guided Bone Regeneration with Microbial Protection of Ornamented SPU Scaffold with Bismuth-Doped Single Crystalline Hydroxyapatite: Augmentation and Cartilage Formation

Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi-nHA ornamentation in promoting osteoblast phenotype progression with microbial protection (on-demand) for GBR applications.

Covalent cross-links in polyampholytic chitosan fibers enhances bone regeneration in a rabbit model

Chitosan fibers were prepared in citric acid bath, pH 7.4 and NaOH solution at pH 13, to form ionotropically cross-linked and uncross-linked fibers, respectively. The fibers formed in citric acid bath were further cross-linked via carbodiimide chemistry; wherein the pendant carboxyl moieties of citric acid were used for new amide bond formation. Moreover, upon covalent cross-linking in the ionically gelled citrate-chitosan fibers, incomplete conversion of the ion pairs to amide linkages took place resulting in the formation of a dual network structure. The dual cross-linked fibers displayed improved mechanical property, higher stability against enzymatic degradation, hydrophobicity and superior bio-mineralization compared to the uncross-linked and native citrate cross-linked fibers. Additionally, upon cyclic loading, the ion pairs in the dual cross-linked fibers dissociated by dissipating energy and reformed during the relaxation period. The twin property of elasticity and energy dissipation mechanism makes the dual cross-linked fiber unique under dynamic mechanical conditions. The differences in the physico-chemical characteristics were reflected in protein adsorption, which in turn influenced the cellular activities on the fibers. Compared to the uncross-linked and ionotropically cross-linked fibers, the dual cross-linked fibers demonstrated higher proliferation and osteogenic differentiation of the MSCs in vitro as well as better osseous tissue regeneration in a rabbit model.

Excavating the Role of Aloe Vera Wrapped Mesoporous Hydroxyapatite Frame Ornamentation in Newly Architectured Polyurethane Scaffolds for Osteogenesis and Guided Bone Regeneration with Microbial Protection

Guided bone regeneration (GBR) scaffolds are unsuccessful in many clinical applications due to a high incidence of postoperative infection. The objective of this work is to fabricate GBR with an anti-infective electrospun scaffold by ornamenting segmented polyurethane (SPU) with two-dimensional Aloe vera wrapped mesoporous hydroxyapatite (Al-mHA) nanorods. The antimicrobial characteristic of the scaffold has been retrieved from the prepared Al-mHA frame with high aspect ratio (∼14.2) via biosynthesis route using Aloe vera (Aloe barbadensis miller) extract. The Al-mHA frame was introduced into an unprecedented SPU matrix (solution polymerized) based on combinatorial soft segments of poly(ε-caprolactone) (PCL), poly(ethylene carbonate) (PEC), and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, pristine mHA nanorods are also ornamented into it. An enzymatic ring-opening polymerization technique was adapted to synthesize soft segment of (PCL-PEC-b-PDMS). Structure elucidation of the synthesized polymers is established by nuclear magnetic resonance spectroscopy. Sparingly, Al-mHA ornamented scaffolds exhibit tremendous improvement (175%) in the mechanical properties with promising antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast-like MG63 cells (in vitro), the scaffolds were implanted in rabbits as an animal model by subcutaneous and intraosseous (tibial) sites. Improved in vivo biocompatibilities, biodegradation, osteoconductivity, and the ability to provide an adequate biomimetic environment for biomineralization for GBR of the scaffolds (SPU and ornamented SPUs) have been found from the various histological sections. Early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks were found in the defects filled with Al-mHA ornamented scaffold compared to pristine SPU scaffold. Organ toxicity studies further confirm the absence of appreciable tissue architecture abnormalities in the renal hepatic and cardiac tissue sections. The entire results of this study manifest the feasibility of fabricating a mechanically adequate tailored nanofibrous SPU scaffold based on combinatorial soft segments of PCL, PEC, and PDMS by a biomimetic approach and the advantages of an Aloe vera wrapped mHA frame in promoting osteoblast phenotype progression with microbial protection for potential GBR applications.

Rising trend of diabetes mellitus amongst the undernourished: State -of- the -art review

Diabetes mellitus is prevailing in the malnourished populations congruently in well-nourished ones with an escalating trend in the former group regardless of the absence of obesity as an etiologic determining factor as per the studies in underprivileged sectors of the population. Chronic undernutrition across a lifetime may be an imperative stimulator of diabetes in an individual either by progressively reducing beta cell function alongside islet cell volume and increasing the individual predisposition to other genetic or environmental diabetogenic influences with modifying influence on the course of clinical syndrome. Ketosis resistant insulinopenia is irreversible to the sustained vigorous nutritional convalescence in a substantial fraction of malnourished subjects. It also debunks a latent diabetic stage with insulin resistance reflected by greater insulin requirement in comparison to the patients with type I diabetes with the same beta cell failure fraction and obese type II diabetic patients with equivalent glycemic control gauged by HbA1c levels. Current tendency warrants the replacement of conventional therapy by community oriented theranostic approaches and health programs to curb the epidemic.

Radiopaque Hemocompatible Ruminant-Sourced Gut Material with Antimicrobial Physiognomies for Biomedical Applications in Diabetics

This study comprises the fabrication of a radiopaque gut material with its mechanical properties conforming to the US Pharmacopeia guidelines giving an antimicrobial advantage for suture application, especially in conditions such as diabetes mellitus, which has a high wound infection rate. Schiff base cross-linking iodination of the material is evinced by the spectroscopic studies, and antimicrobial properties owing to released iodine are evinced through in vitro studies. Modified gut sutures demonstrated favorable physicomechanical features such as appropriate tensile strength (440 ± 20 MPa) and knot strength (270 ± 20) alongside a mean radiopacity value of 139.0 ± 10 in comparison with that of the femoral shaft with 160 ± 10. The diabetic model showed absence of clinical signs of infection, supported by wound swab culture and the absence of necrosis in histology. Hemocompatibility studies evinced the absence of contact platelet activation and hemolysis alongside the customary coagulation response. These promising results highlight the stimulating potential of the process in the development of biomedical applications, necessitating persistent studies for its evidence-based applicability, particularly in diabetic patients.