Biofunctionality with a twist: the importance of molecular organisation, handedness and configuration in synthetic biomaterial design

This review highlights the importance of incorporating molecular organisation, spatial configuration and handedness in biomaterial design to arrive at improved native biomolecule interactions.

Evaluation of Osteoconduction of a Synthetic Hydroxyapatite/β-Tricalcium Phosphate Block Fixed in Rabbit Mandibles

(1) Background: This study aimed to evaluate the incorporation of hydroxyapatite/β-tricalcium phosphate blocks grafted in rabbit mandibles. (2) Methods: Topographic characterization of biomaterial was performed through scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX). Ten rabbits randomly received autogenous bone graft harvested from the tibia (Autogenous Group—AG) or synthetic biomaterial manufactured in β-tricalcium phosphate (Biomaterial Group—BG) at their right and left mandibular angles. Euthanasia was performed at 30 and 60 postoperative days; (3) Results: SEM-EDX showed a surface with the formation of crystals clusters. Histological analyses in BG at 30 days showed a slower process of incorporation than AG. At 60 days, BG showed remnants of biomaterial enveloped by bone tissue in the anabolic modeling phase. Histometric analysis showed that mean values of newly formed bone-like tissue in the AG (6.56%/9.70%) were statistically higher compared to BG (3.14%/6.43%) in both periods, respectively. Immunohistochemical analysis demonstrated early bone formation and maturation in the AG with more intense osteopontin and osteocalcin staining. (4) Conclusions: The biomaterial proved to be a possible bone substitute, being incorporated into the receiving bed; however, it showed delayed bone incorporation compared to autogenous bone.

Gastrointestinal synthetic epithelial linings

Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the small intestine, given its role in drug and nutrient absorption and identified catalase as an essential enzyme with the potential to catalyze polymerization and growth of synthetic biomaterial layers. We demonstrated that the polymerization of dopamine by catalase yields strong tissue adhesion. We characterized the mechanism and specificity of the polymerization in segments of the gastrointestinal tracts of pigs and humans ex vivo. Moreover, we demonstrated proof of concept for application of these gastrointestinal synthetic epithelial linings for drug delivery, enzymatic immobilization for digestive supplementation, and nutritional modulation through transient barrier formation in pigs. This catalase-based approach to in situ biomaterial generation may have broad indications for gastrointestinal applications.

Immunotherapy via PD-L1–presenting biomaterials leads to long-term islet graft survival

Antibody-mediated immune checkpoint blockade is a transformative immunotherapy for cancer. These same mechanisms can be repurposed for the control of destructive alloreactive immune responses in the transplantation setting. Here, we implement a synthetic biomaterial platform for the local delivery of a chimeric streptavidin/programmed cell death-1 (SA-PD-L1) protein to direct “reprogramming” of local immune responses to transplanted pancreatic islets. Controlled presentation of SA-PD-L1 on the surface of poly(ethylene glycol) microgels improves local retention of the immunomodulatory agent over 3 weeks in vivo. Furthermore, local induction of allograft acceptance is achieved in a murine model of diabetes only when receiving the SA-PD-L1–presenting biomaterial in combination with a brief rapamycin treatment. Immune characterization revealed an increase in T regulatory and anergic cells after SA-PD-L1-microgel delivery, which was distinct from naïve and biomaterial alone microenvironments. Engineering the local microenvironment via biomaterial delivery of checkpoint proteins has the potential to advance cell-based therapies, avoiding the need for systemic chronic immunosuppression.

Synthesis and Characterization of a Highly Ordered Mesoporous Bio-glass

A highly ordered mesoporous bio-glass has been successfully prepared by the sol-gel method, in which copolymer pluronic P123 was used as a structure-creating template. The obtained material has the mesoporous structure with the high value of specific surface area (395.6 m2 /g) and the 2D hexagonal pore architecture with the pore sizes from 5.5 to 7 nm. The ‘‘in vitro’’ experiment was effectuated by soaking the bio-glass powder in the simulated body fluid (SBF). The obtained results confirmed the bioactivity of the synthetic biomaterial through the quick formation of a hydroxyapatite layer after 1 day of immersion. Keywords: Bio-glass, pore size, mesoporous, bioactivity, ‘‘in vitro’’.

Surface modification of polymeric electrospun scaffolds via a potent and high-affinity integrin α4β1 ligand improved the adhesion, spreading and survival of human chorionic villus-derived mesenchymal stem cells: a new insight for fetal tissue engineering

Presenting a potent and high-affinity integrin ligand on the surface of synthetic biomaterial scaffolds improves stem cell-biomaterial interactions for fetal tissue engineering.

Nanosized hydroxyapatite and β-tricalcium phosphate composite: Physico-chemical, cytotoxicity, morphological properties and in vivo trial

The objective of this work was to characterize the properties of a synthetic biomaterial composite with nanoparticles size (Blue Bone). This biomaterial is a composite recommended for dental and orthopedic grafting surgery, for guided bone regeneration, including maxillary sinus lift, fresh alveolus filling, and treatment of furcation lesions. The nano biomaterials surface area is from 30% to 50% higher than those with micro dimensions. Another advantage is that the alloplastic biomaterial has homogeneous properties due to the complete manufacturing control. The analyzed biomaterial composite was characterized by XRD, cytochemistry, scanning electron microscopy, porosimetry and in vivo experiments (animals). The results showed that the analyzed biomaterial composite has 78.76% hydroxyapatite [Ca5(PO4)3(OH)] with monoclinic structure, 21.03% β-tricalcium phosphate [β -Ca3(PO4)2] with trigonal structure and 0.19% of CaO with cubic structure, nanoparticles with homogeneous shapes, and nanoporosity. The in vivo experiments showed that the composite has null cytotoxicity, and the site of insertion biomaterials has a high level of vascularization and bone formation. The conclusion is that the synthetic biomaterial with Blue Bone designation presents characteristics suitable for use in grafting surgery applications.

Histological Evaluation of a New Beta-Tricalcium Phosphate/Hydroxyapatite/Poly (1-Lactide-Co-Caprolactone) Composite Biomaterial in the Inflammatory Process and Repair of Critical Bone Defects

Background: The use of biomaterials is commonplace in dentistry for bone regeneration. The aim of this study was to evaluate the performance of a new alloplastic material for bone repair in critical defects and to evaluate the extent of the inflammatory process. Methods: Forty-five New Zealand rabbits were divided into five groups according to evaluation time (7, 14, 30, 60, 120 days), totaling 180 sites with six-millimeter diameter defects in their tibiae. The defects were filled with alloplastic material consisting of poly (lactide-co-caprolactone), beta-tricalcium phosphate, hydroxyapatite and nano-hydroxyapatite (BTPHP) in three different presentations: paste, block, and membrane. Comparisons were established with reference materials, such as Bio-ossTM, Bio-oss CollagenTM, and Bio-gideTM, respectively. The samples were HE-stained and evaluated for inflammatory infiltrate (scored for intensity from 0 to 3) and the presence of newly formed bone at the periphery of the defects. Results: Greater bone formation was observed for the alloplastic material and equivalent inflammatory intensity for both materials, regardless of evaluation time. At 30 days, part of the synthetic biomaterial, regardless of the presentation, was resorbed. Conclusions: We concluded that this novel alloplastic material showed osteoconductive potential, biocompatibility, low inflammatory response, and gradual resorption, thus an alternative strategy for guided bone regeneration.