Biomaterials for trauma

Contact persons

Sune Larsson, Professor

Gry Hulsart Billström, PhD

We are involved in the development and evaluation of new biomaterials by using preclinical, as well as, clinical models

One of our main goals is to take forward materials that can be used to heal large bone defects after trauma. Secondly, we aim to optimize compounds that will stimulate bone healing in patients with compromised healing capacity. 

µCT reconstruction of a premixed calcium phosphate cement in a uni-cortical defect
µCT reconstruction of a premixed calcium
phosphate cement in a uni-cortical defect

These challenges require different types of bone substitutes and a crucial part of the development of new materials is conducted by the groups of Polymer ChemistryBioMaterial Systems and Materials in Medicine, all situated at Ångström Laboratory, a part of the Technical Faculty at Uppsala University.

Before new biomaterials can be transitioned into clinical treatments, the specific biological responses of new materials have to be evaluated. Using preclinical as well as clinical models we aim to improve understanding of the biological interactions with biomaterials as well as proofing biological safety and exploring treatment options.

µCT cross section of a bone adhesive
µCT cross section of a bone adhesive

Ongoing project – basic research meets clinical needs

For a long period there has been an unmet need in the orthopaedic community for an adhesive material, a “bone glue”, that will allow fixation of small bone and cartilage fragments where conventional nails or screws for various reasons do not provide sufficient fixation.

In a recently initiated research project the intention is to optimize and evaluate a new type of adhesive. The project is part of a collaboration with European academics and industrial research partners. 

In another project, we have over the last years been part of developing a new polymer based carrier that can be used for bone induction. The biological efficacy of the inductive molecules is higher than with previously used carriers, which means that the dosage of the bio-inductive material can be lowered dramatically while still, the same bone forming capacity will be achieved. 

Additionally, we are working on a replacement platform for in vitro testing. Biomaterial evaluation requires many different in vitroassays to initially assess biocompatibility; however, translation between in vitroand in vivoassays has proven to be challenging. In accordance to the three R’s – Reduction, refinement, and replacement – we are developing a bioreactor platform to evaluate biomaterials in a 3D environment and in contact to live bone tissue. 

Left picture is a histology section of bone forming in an injectable hydrogel. Right picture collagen alignment visualised through polarised light.
Left picture is a histology section of bone forming in an injectable hydrogel.
Right picture collagen alignment visualised through polarised light.

 
µCT image of a healing fracture in fake colours.
µCT image of a healing fracture in fake colours.

Evaluating biomaterials with a wide range of techniques – from cells to animal models 

Employing an array of experimental in vitroas well as in vivo models, various modifications of the material will be evaluated with the aim to optimize both biological and mechanical properties.

By using the state of the art micro-CT in combination with PET and SPECT imaging (availble at the PRECLINICAL PET-MRI PLATFORM), longitudinal information can be gathered describing events at the interface between the biological surfaces and the partially interpositioned adhesive material.

In addition, conventional hard tissue and histochemical assessments will be used for increasing the knowledge on how the adhesive properties are being executed. Static and dynamic mechanical testing will be used for describing the mechanical competence over time when subjected to static as well as repetitive loading. The direct response of cells is measured through various cell assays while qPCR analysis is used to analyse the impact of biomaterials on gene expression level. Soon our new bioreactor platform will be used to explore tissue- material interphases in vitro, which will give valuable insight for further translation towards clinical use. 

We are combining our basic biological research with our clinical use and biomaterial collaborations to find more effective ways of healing after trauma.

Group members:

Sune Larsson, Professor

Gry Hulsart Billström, PhD

Christina Stelzl, MSc

Our latest articles

  • Paidikondala, Maruthibabu; Wang, Shujiang; Hilborn, Jöns; Larsson, Sune et al.

    Impact of Hydrogel Cross-Linking Chemistry on the in Vitro and in VivoBioactivity of Recombinant Human Bone Morphogenetic Protein-2

    Part of ACS Applied Bio Materials, 2019.

  • Hulsart Billström, Gry; Janson, Oscar; Engqvist, Håkan; Welch, Ken et al.

    Thromboinflammation as bioactivity assessment of H2O2-alkali modified titanium surfaces

    Part of Journal of materials science. Materials in medicine, 2019.

    Open access
  • Yan, Hongji; Casalini, Tommaso; Hulsart Billström, Gry; Wang, Shujiang et al.

    Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation

    Part of Biomaterials, p. 190-202, 2018.

  • Christersson, Albert; Larsson, Sune; Sandén, Bengt

    Clinical outcome after plaster cast fixation for 10 days versus 1 month in reduced distal radius fractures: A prospective randomized study

    Part of Scandinavian Journal of Surgery, p. 82-90, 2018.

  • Larsson, Sune

    Clavicula fractures: considerations when plating

    Part of Injury, p. S24-S28, 2018.

  • Christersson, Albert; Larsson, Sune; Sörensen, Jens

    Presurgical localization of infected avascular bone segments in chronic complicated posttraumatic osteomyelitis in the lower extremity using dual-tracer PET/CT.

    Part of EJNMMI Research, 2018.

    Open access
  • Hulsart Billström, Gry; Selvaraju, Ramkumar; Estrada, Sergio; Lubberink, Mark et al.

    Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept

    Part of Journal of Controlled Release, p. 178-186, 2018.

    Open access
  • Augat, Peter; Larsson, Sune

    Plating of fractures: current treatments and complications

    Part of Injury, p. S1-S1, 2018.

  • Robo, Céline; Hulsart Billström, Gry; Nilsson, Malin; Persson, Cecilia et al.

    In vivo response to a low-modulus PMMA bone cement in an ovine model

    Part of Acta Biomaterialia, p. 362-370, 2018.

  • Mei, Xueshuang; Atturo, Francesca; Wadin, Karin; Larsson, Sune et al.

    Human inner ear blood supply revisited: the Uppsala collection of temporal bone - an international resource of education and collaboration

    Part of Upsala Journal of Medical Sciences, p. 131-142, 2018.

    Open access
  • Schart-Moren, Nadine; Larsson, Sune; Rask-Andersen, Helge; Li, Hao et al.

    Three-Dimensional Analysis of the Fundus of the Human Internal Acoustic Canal

    Part of Ear and Hearing, p. 563-572, 2018.

  • Atturo, Francesca; Schart-Moren, Nadine; Larsson, Sune; Rask-Andersen, Helge et al.

    The Human Cochlear Aqueduct and Accessory Canals: a Micro-CT Analysis Using a 3D Reconstruction Paradigm

    Part of Otology and Neurotology, p. e429-e435, 2018.

  • Lindahl, Katarina; Astrom, Eva; Dragomir, Anca; Symoens, Sofie et al.

    Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy

    Part of Bone, p. 268-277, 2018.

  • Gunnarsson, Anna-Karin; Gunningberg, Lena; Larsson, Sune; Jonsson, Kenneth B. et al.

    Cranberry juice concentrate does not significantly decrease the incidence of acquired bacteriuria in female hip-fracture patients receiving urine catheter: a double-blind randomised trial

    Part of Clinical Interventions in Aging, p. 137-143, 2017.

    Open access
  • Enghoffsalen, Akademiska sjukhuset, ingång 50, Uppsala 2017-02-24 09:15

    Hulsart Billström, Gry

    Bone Regeneration with Cell-free Injectable Scaffolds

    Open access