We consider the optimal scaffold design problem associated with a previously considered, three-dimensional, time-dependent model for scaffold-mediated bone regeneration. We prove existence of optimal scaffold designs and present numerical evidence that optimized scaffolds mitigate stress shielding effects resulting from exterior fixation of the scaffold at the defect site.

Translating scientific discoveries in tissue engineering and regenerative medicine (TE/RM) into clinically adopted therapies is hindered by fragmented development pipelines, regulatory and manufacturing challenges, and limited funding. Despite substantial investment by the U.S. National Institutes of Health (NIH), few NIH-funded TE/RM projects achieve commercialization or regulatory approval by the US Food and Drug Administration. The gap between academic innovation and clinical implementation is particularly evident in the dental, oral, and craniofacial (DOC) domain, where market and reimbursement constraints further restrict translation. To address these barriers, the National Institute of Dental and Craniofacial Research established the Dental, Oral and Craniofacial Tissue Regeneration Consortium (DOCTRC), comprising two nationwide Resource Centers tasked with guiding promising technologies from universities and small businesses through preclinical validation toward clinical adoption. This translational science case study outlines DOCTRC’s translational model, highlighting lessons learned from five cohorts of interdisciplinary translational project teams, strategies for navigating manufacturing and regulatory pathways, and approaches for aligning academic innovation with clinical and market needs. The unique impact of the DOCTRC framework demonstrates how disciplined product development activities, non-dilutive funding mechanisms, and a comprehensive support ecosystem can accelerate technology translation, offering a scalable model for other biomedical fields.

Hollow fibre membrane bioreactors provide a fast and efficient method for engineering functional tissue for use in medical treatments. Flow is utilised to overcome mass transport limitations by perfusing a nutrient-rich culture medium through the fibre lumen, which can then transport along the fibre lumen or across the porous membrane wall. Cells seeded at the outer membrane wall consume the nutrient and subsequently produce waste metabolites, which are transported away through an external extra-capillary space (ECS) along with excess nutrient. We present and investigate a two-dimensional axisymmetric model for fluid flow and solute transport through a single-fibre bioreactor configuration, with cells seeded to the external fibre wall. Fluid flow is modelled by steady lubrication and Darcy equations, which are coupled to the solute transport problem modelled by a system of advection–diffusion equations, supplemented with a reaction term to model the cell layer. Our model analysis reveals how spatially varying wall permeability distributions can be utilised to provide uniform nutrient delivery to a spatially uniform, homogeneous cell population. We also reveal how maximising the transmural pressure drop across the membrane wall is the dominant mechanism for waste removal rather than traditional experimental methods of flushing the ECS.

Halloysite nanotubes (HNTs) are hollow clay nanotubes in the nanometer size range, made up of double-layered aluminum silicate mineral layers. HNTs represent an extremely versatile, safe, and biocompatible nanomaterial, used in a wide range of applications in biomedicine and nanomedicine. For example, they are used as transporters for the controlled release of drugs or genes, in tissue engineering, in the isolation of stem cells and cancer cells, and in bioimaging. Consequently, the assessment of the biocompatibility of HNTs has acquired considerable importance. In recent years, HNT composites have attracted attention due to their improved biocompatibility, compared to HNTs, suggesting potential for applications in tissue engineering or as vehicles for drugs or genes. In this review, recent advances in the application of HNTs and HNT composites in biomedicine are discussed to provide a valuable guide to scientists in the design and development of viable, functional bio-devices for biomedical applications.

The implantation of new biomedical devices into living animals without any previous toxicity or biocompatibility evaluation is possible under current legislation. The HET–CAM (Hen Egg Test–Chorionallantoic Membrane) test offers a partially immunodeficient, borderline in vitro/in vivo test system that allows the simulation of transplantation experiments to obtain biocompatibility data prior to animal testing. A collagen type I/III scaffold, designed for tissue regeneration, was tested for angiogenetic properties and biocompatibility patterns. A significant angiogenetic stimulus caused by the collagen scaffold material was observed. Altering biocompatibility patterns by incubation with the potentially hazardous chemicals acridine orange and ethidium bromide led to severe vessel thrombosis and a foreign body tissue response. CAM testing of biomaterials and tissue engineered products allows selection of the most suitable biomaterial and the elimination of unsuitable materials from animal experiments, leading to a refinement of testing procedures and a reduction in the number of animals required for biocompatibility testing.

Chitosan is one of the most versatile biopolymers available with established properties such as antimicrobial, antitumor, anti-inflammatory, mucoadhesive, and more. It has been in biomedical research for long, but still the bench-to-bedside translation is hampered because of viscosity and solubility issues. The only commercial application of chitosan has been in hemostatic dressings. Chitosan oligosaccharide (COS), on the other hand, is highly promising in a similar research area where chitosan's limitations come into the way. COS is highly soluble in water, and its viscosity is very less than that of the parent chitosan. Although COS retains properties very similar to those of chitosan, there has been minuscule volume of research on this water-soluble chitosan. COS has been successfully used as a drug delivery vehicle in various research. COS has also shown to have osteogenic ability. It has been used as a coating on experimental orthopedic implants because of its antibacterial properties. As of now, COS is not a much-explored biopolymer, although it could be an important biopolymer for its capacity in biomedical research. This article reviews various properties and reports of COS relevant for biomedical applications.

In this paper, we revisit our previous work in which we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. The underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearization of the underlying multiphase model (whose nonlinearity poses a significant challenge for such analyses), we obtain, by means of multiple-scale homogenization, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics, via so-called unit-cell problems that provide permeability tensors to parameterize the macroscale description. In our previous work, the cell problems retain macroscale dependence, posing significant challenges for computational implementation of the eventual macroscopic model; here, we obtain a decoupled system whereby the quasi-steady cell problems may be solved separately from the macroscale description. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.

In recent years, tissue engineering has helped to reduce hospital stays and deaths caused by skin wounds. Scaffolds are one of the main factors that influence the success of any tissue graft. Collagen is one of the main components of the extracellular matrix, and there has been much interest in new sources for application as a biomaterial. In this work, a tissue engineering scaffold was developed using the electrospinning technique. The chicken skin was used as an alternative source to obtain collagen. The combination of this collagen with elastin was successfully electrospun, and a distribution of diameters was obtained, less than 100 nm. In vitro tests showed the adhesion and proliferation of the cells, as well as an absence of cytotoxicity from non–cross-linked scaffolds and scaffolds that were cross-linked with carbonyldiimidazole. The structure and composition of the developed scaffolding provide a favorable environment for cell growth and generating a skin substitute.

Biomimicry is a desirable quality of tissue engineering scaffolds. While most of the scaffolds reported in the literature contain a single pore size or porosity, the native biological tissues such as cartilage and skin have a layered architecture with zone-specific pore size and mechanical properties. Thus, there is a need for functionally graded scaffolds (FGS). EHD-jet 3D printing is a high-resolution process and a variety of polymer solutions can be processed into 3D porous scaffolds at ease, overcoming the limitations of other 3D printing methods (SLS, stereolithography, and FDM) in terms of resolution and limited material choice. In this paper, a novel proof of concept study on fabrication of porous polycaprolactone-based FGS by using EHD-jet 3D printing technology is presented. Organomorphic scaffolds, multiculture systems, interfacial tissue engineering, and in vitro cancer metastasis models are some of the futuristic applications of these polymeric FGS.

We derive an effective macroscale description for the growth of tissue on a porous scaffold. A multiphase model is employed to describe the tissue dynamics; linearisation to facilitate a multiple-scale homogenisation provides an effective macroscale description, which incorporates dependence on the microscale structure and dynamics. In particular, the resulting description admits both interstitial growth and active cell motion. This model comprises Darcy flow, and differential equations for the volume fraction of cells within the scaffold and the concentration of nutrient, required for growth. These are coupled with Stokes-type cell problems on the microscale, incorporating dependence on active cell motion and pore scale structure. The cell problems provide the permeability tensors with which the macroscale flow is parameterised. A subset of solutions is illustrated by numerical simulations.

Laser-assisted bioprinting is one among several technologies that are being developed in the recent and growing field of bioprinting. Bioprinting is defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacology, and basic cell biology studies. We describe the physical parameters that need to be tuned for laser-assisted bioprinting of materials and cells, with high throughput and controlled printing resolution. We present its applications for printing cells and tissue-relevant biomaterials, both in vitro and in vivo. Finally, we discuss how this technique may help in reproducing the local cell micro-environment and dealing with tissue complexity and heterogeneity for fabricating functional tissue-engineered 3D constructs.

Since the emergence of tissue engineering (TE), numerous researchers, particularly in the areas of materials, biological science, and engineering, have aimed to provide viable substitutes for the repair and regeneration of musculoskeletal and organ tissues. Bone TE has been extensively explored to mimic the anatomical geometry of bone with varied pore size distribution and varying mechanical properties in a radial direction (a functional gradient). This TE approach was explored to promote faster functional recovery of defective bones due to congenital, traumatic, or degenerative reasons. The present study integrated an appropriate additive manufacturing or rapid prototyping technique with automated computer-aided design models. This process was applied to the manufacture of a functionally graded scaffold (FGS). The FGS system takes into consideration both microscale anatomical geometries and mechanical properties of the native bone via an established porosity-stiffness relationship. Experimental verification of the FGS model was carried out by the fabrication of a femur bone segment using a selective laser sintering system. The physical femur model demonstrated good replication of the FGS structure that was generated. Future work aims to implement the FGS system for other musculoskeletal and organ tissues and integrate the current work with the authors’ in-house developed “computer aided system for tissue scaffolds” or CASTS system.

In recent years, biomaterial investigators have increasingly focused their research on hydrogels and their capability to be fabricated into tissue engineering scaffolds. Although several fabrication methods have been used to produce hydrogel scaffolds, those methods are unable to routinely produce three-dimensional submicron and nanoscale scaffolds with precise control of the geometry, a crucial factor necessitated by the recent developments in the field of tissue engineering. Femtosecond laser-induced two-photon polymerization is a promising technique that fulfills these requirements. In our work, we used a femtosecond laser to fabricate three-dimensional submicron-scale scaffolds with poly(ethylene glycol) (PEG). The modulus, dimensions, and shape of the scaffold can be readily adjusted by changing both the laser parameters and the molecular weight of the PEG prepolymer. With the femtosecond laser, we also fabricated two-dimensional topographical patterns, which have important applications in basic biological research. To improve the throughput of femtosecond laser fabrication, we integrated the femtosecond direct-write process with a nano-imprint process by which the femtosecond laser is used to produce nano-patterned molds. We then carried out nanoimprinting to transfer the nanofeatures in the mold to the hydrogel in a massively parallel fashion.

Optimal nutrition depends on the multiple complex functions performed by the gastrointestinal tract, which range from basic functions such as storage, conduit and mechanical processing to more finely regulated capabilities such as vectorial transport, immune defence and cell signalling. Surgical strategies to supply lacking gastrointestinal tract tissues have relied on either replacement by proxy (surgical substitution) or the introduction of prostheses. Tissue engineering seeks to replace missing tissues with engineered tissues that more accurately reproduce the native physiological and anatomical milieu. It is now possible to engineer several areas of the gastrointestinal tract with high fidelity, and to employ tissue-engineered bowel in replacement in animal models. These replacement models have reflected excellent anatomical and physiological recapitulation of native bowel by the tissue-engineered constructs in vivo.