Dr. Grover’s PhD (supervised by Prof. Jake Barralet) was titled ‘Cold-setting properties of Ca₃(PO₄)₂ – H₄P₂O₇ – H₂O mixtures’ and focussed principally on the formulation and evaluation of a novel calcium phosphate cement system for bone replacement. Following the completion of his PhD, Dr. Grover took a postdoctoral position at McGill University (School of Dentistry) where he spent two years on projects funded by Smith and Nephew and the CIHR. In this time, his work took a more biological emphasis and he developed an expertise in the control of bone mineralisation. In particular, he became interested in how condensed phosphate species could play both an inhibitory and stimulatory role in bone mineralisation. 

On his return to the University of Birmingham in 2006 (School of Chemical Engineering), Dr. Grover began to apply the knowledge he had gained in the control of bone mineralisation to enable the rational design of biomaterials which were able to interact with biological pathways responsible for tissue formation. In the years since his return to the UK, Dr. Grover has worked extensively on the regeneration of the hard/soft tissue interface and is currently particularly interested in the control of mineral formation within soft-solid matrices with structures similar to those of the extracellular matrix. He also currently works on evaluating how cell encapsulation influences the mechanical properties of hydrogels and vice versa.

Dr. Grover has a PGCert in teaching in further education, his current teaching responsibilities include:

•  Module coordinator and principle lecturer on Bioscience for Engineers (Level H and Level M)
•  Coordinator for Bioscience for Engineers practical week.
•  Module coordinator and principle lecturer on Modern Genome Based Bioscience/Frontier Interdisciplinary Bioscience (Level M)
•  Module coordinator for MSc summer research projects (Level M)
•  Lecturer on Sustainable Development module (Level H)

He has also given lectures at Keele University, the University of Wuerzburg and has been invited to lecture at the Technical University of Vienna.

Dr. Grover’s research focuses on the development and characterisation of materials for the regeneration of diseased and damaged tissues. His work has largely focussed on the regeneration of bone and bone interfacing tissues, but he has also published on the delivery of fibroblasts and keratinocytes for skin regeneration. Dr. Grover has developed a particular interest in how interfaces form, both within tissues (ligament – bone, cartilage – bone) and when foreign bodies are introduced into a biological system (electrodes within cell cultures). Below is a summary of four of his current principle areas of activity.

Regenerating the hard/soft tissue interface

Throughout the body, there are numerous regions where soft tissues (ligament, tendon, cartilage) interface with bone. The interfaces in these tissues are specially structured so that stress is dissipated across the interface. Synthetic replacements do not satisfactorily restore this interface and so typically fail at the interface. Within this area Dr. Grover is:

• Developing tissue engineered bone to bone ligament replacements (BBSRC funded project) using fibrin and a selection of different sparingly soluble ceramics with the University of California – Davis.
• Reinforcing tissue engineered ligament replacements using spring made from a titanium alloy (Furlong Charitable Foundation funded)
• Investigating how interfaces similar to those found in vivo may be formed in vitro with and without the involvement of a cell population. 

Polymer gel encapsulation of cells

The clinical application of cells for the treatment of a range of pathologies requires a fundamental knowledge of how encapsulation may affect cell behaviour and how cell culture conditions and the conditions found in vivo may influence gel degradation. In this area we are:

• Systematically evaluating how cell encapsulation affects the mechanical properties of hydrogels, as determined using rheology and gross mechanical testing (EU – FP7 funded project – NanoBioTouch).
• Observing how hydrogel matrices can release cells into the surrounding milieu and investigating whether the encapsulated cell population continues to produce molecules of particular therapeutic value (e.g. VEGF) (EU – FP6 funded project – NanoBioTact). 
• Determining how cells respond to encapsulation. Do they maintain their phenotype? Will they continue to proliferate? Can they produce an extracellular matrix within the hydrogel matrix? (NanoBioTact).
• Evaluate how minor additions of ions found in culture medium and mineral (both dispersed and in relatively large particulate form) can influence the degradation and mechanical properties exhibited by hydrocolloids and hydrogels.
• Determine whether it is possible to enhance matrix production using ultrasonic treatment (work funded by the Malaysian government).
• Evaluating whether it is possible to measure in real-time the responses of cells to applied loads and thereby use cells to detect touch (NanoBioTact).

Calcium phosphate materials chemistry

Although there has been a lot of research in recent years on the development of calcium phosphate based materials for bone replacement applications, there is still much to be learnt about how these materials are formed and interact with bodily systems and relatively few have researched the role that condensed phosphates play in biomineralisation, let alone how they can be used as hard tissue replacements. Currently we are:

• Investigating how amorphous materials (orthophosphate and condensed phosphate) are involved in the process of biomineralisation and how these materials may be harnessed to form bioresponsive ceramics.
• Developing calcium phosphate cement formulations with properties that may enhance clinical uptake e.g. controlled setting materials and controlled degradation materials (Smith and Nephew and EPSRC funded).
• Surface modification of calcium phosphate salts to enable gene transfection and controlled release of therapeutic substances.
• Structure calcium phosphate salts by controlling process conditions (AWM funded).

Dr Grover also has an interest in the development and use of alternative cement formulations in medical applications. At present we use only a small selection of compositions and yet many inorganic cements are formed from ions which can be processed and cleared from the body. Dr. Grover has had a funded PhD project in this area (Chinese government scholarship).

Controlling mineralisation

Many industrial applications require nanocrystalline salts that exhibit very high specific surface areas. In order to produce such salts it is often necessary to employ high-temperatures, expensive catalysts or environmentally harmful solvents. Salts with such properties are, however, widely found in nature. Dr Grover is:

• Evaluating how cheap proteins (e.g. albumin) may be used to adjust crystal habit in industrial relevant minerals such as magnetite (BBSRC funded PhD).
• Determining how amorphous minerals with high specific surface area may be stabilised in the presence of protein found in the body (CIHR funded project).

It is hoped that the outcomes of this research area will directly feed into UK industry in the development of more economical and greener processes for the production of industrially important minerals.

Other research commitments

• Member of the cementitious materials committee of the IOM³
• Member of the Biochemical Engineering Subject Group (BESG) steering committee (IChemE)
• Member of the PSIBS (Physical Sciences Imaging the Biomedical Sciences) Doctoral Training Centre steering committee.
• Member of the editorial board for Advances in Applied Ceramics and Drug Delivery Letters
• Chair of the 2010 cement and concrete science meeting (University of Birmingham).
• Reviewer for more than thirty journals, including European Cells and Material, Biomaterials, Tissue Engineering, Chem Comm, Langmuir, Journal of Materials Chemistry.
• Reviewer for the BBSRC, MRC, Healthcare KTN and the Hong Kong Research Council
• Member of the School of Chemical Engineering research committee

 

Barralet JE, Gibson IR, Grover LM, Gaunt T, Wright AJ. Preparation of macroporous calcium phosphate tissue engineering scaffold. Biomaterials 2002;23:15:3063-3072. 

Gbureck U, Grolms O, Barralet, JE, Grover LM, Thull R. Mechanical activation and setting reaction of ß-tricalcium phosphate. Biomaterials 2003;24:23:4123-4131.

Grover LM, Knowles JC, Barralet, JE. In vitro ageing of a brushite calcium phosphate cement. Biomaterials 2003;24:4133-41.

Barralet JE, Hofmann M, Grover LM, Gbureck U. High Strength Apatitic Cement by Modification with α-Hydroxy Acid Salts. Adv. Mater. 2003;15:2091-2095

Gbureck U, Barralet, JE, Spatz K, Grover LM, Thull R. Ionic Modification of Calcium Phosphate Cement Viscosity Part I: Hypodermic injection and Strength Improvement of Apatite Cement. Biomaterials 2004;25:2187-2195.

Barralet, JE, Grover LM. Gbureck U. Ionic Modification of Calcium Phosphate Cement Viscosity Part II: Hypodermic injection and Strength Improvement of Brushite Cement. Biomaterials 2004;25:2197-2203.

Gbureck U, Knappe O, Grover LM, Barralet JE. Antimicrobial potency of alkali ion substituted calcium phosphate cements. Biomaterials 2005;26:6880-6886.

Grover LM, Gbureck U, Wright AJ, Barralet JE. Cement formulations in the calcium phosphate H₂O-H₃PO₄-H₄P₂O₇ system. J. Am. Ceram. Soc. 2005; 24:4133-4141.

Grover LM, Gbureck U, Young AM, Wright AJ, Barralet JE. Temperature dependent setting kinetics and mechanical properties of beta-TCP-pyrophosphoric acid bone cement. Journal of Materials Chemistry 2005;15:46:4955-62.

Grover LM, Gbureck U, Wright AJ, Tremayne M, Barralet JE. Biologically mediated resorption of brushite cement in vitro. Biomaterials 2006;27:10:2178-85.

Gorst NJS, Perrie Y, Gbureck U, Hutton AL, Hofmann MP, Grover LM, Barralet JE. Effects of fibre reinforcement on the mechanical properties of brushite cement. Acta Biomaterialia 2006;2:1:95-102.

Xia ZD, Grover LM, Huang YZ, Adamopoulos LE, Gbureck U, Triffitt JT, Shelton RM, Barralet JE. In vitro biodegradation of three brushite calcium phosphate cements by a macrophage cell-line. Biomaterials 2006;27:26:4557-65.

Gbureck U, Hölzel T, Biermann I, Barralet JE, Grover LM. Preparation of tricalcium phosphate/calcium pyrophosphate structures via rapid prototyping. Journal of Materials Science-Materials In Medicine 2008;19:4:1559-1563.

Collins NJ, Leeke GA, Bridson RH, Hassan F, Grover LM. The influence of silica on pore diameter and distribution in PLA scaffolds produced using supercritical CO₂. Journal of Materials Science-Materials In Medicine 2008;19:4:1497-1502.

Grover LM, Kumarasami B, Hofmann MP, Gbureck U, Barralet JE. Frozen delivery of brushite calcium phosphate cement pastes. Acta Biomaterialia 2008;4:6:1916-1923.

Hunt NC, Shelton RM, Grover LM. An Alginate Hydrogel Matrix for the Localised Delivery of a Fibroblast/ Keratinocyte Co-Culture. Biotechnology Journal 2009;4:5:730-737.

Hunt NC, Shelton RM, Grover LM. Encapsulation of fibroblasts in alginate hydrogels causes reversible mitotic and metabolic inhibition Biomaterials 2009;30:32:6435-6443.

Tan YN, Liu Y, Grover LM, Huang BY. Wear behaviour of light-cured dental composites filled with porous glass-ceramic particles 2010;3:1:77-84.

Jiang PJ, Patel S, Gbureck U, Caley R, Grover LM. Comparing the efficacy of three bioceramic matrices for the release of vancomycin hydrochloride. J Biomed Mater Res 2010;93B:1:51-58.

Collins NJ, Bridson RH, Leeke GA, Grover LM. Particle seeding enhances interconnectivity in a polymeric scaffold formed using supercritical CO2.’ Acta Biomaterialia 2010;6:3:1055-1060.

Hunt NC and Grover LM. Cell encapsulation using biopolymer gels. Biotechnology Letters 2010;32:733-742.

Jiang PJ, Wynn-Jones G, Grover LM. A calcium phosphate cryogel for alkaline phosphatase encapsulation. Journal of Materials Science 2010:45:19: 5257-5263.

Smith AM, Fonseca MJ, Grover LM, Bakalis S. Alginate loaded liposomes can protect encapsulated alkaline phosphatise functionality when exposed to gastric pH. J Agric Food Chem 2010:58:8: 4719–4724.

Hunt NC, Smith AM, Gbureck U, Shelton RM, Grover LM. Encapsulation of fibroblasts causes accelerated alginate hydrogel degradation. Acta Biomaterialia; 2010:6:9: 3649–3656.

Paxton JZ, Grover LM, Maher P, Donnelly K, Keatch RP, Baar K. Engineering functional ligament from bone to bone. 2010;16:11:3515-3525.

Paxton JZ, Donnelly K, Keatch RP, Baar K, Grover LM. Factors affecting in vitro musculoskeletal interface longevity and strength. Annals of Biomedical Engineering 2010;38:6:21552166.

Jahromi SH, Grover LM, Paxton JZ, Smith AM. Degradation of polysaccharide hydrogels seeded with bone marrow stromal cells . Journal of the Mechanical Behavior of Biomedical Materials 2011;4:7:1157-1166.

Karmouty-Quintana H, Tamimi F, McGovern TK, Grover LM,. Martin JG, Barralet JE. Sustained steroid release in pulmonary inflammation model. Biomaterials 2010;31:23:6050-6059.

Hadley MJ, Rowson NA, Wright AJ, Grover LM. Acicular nanoparticles formed through coprecipitation of iron salts in the presence of bovine serum albumin. Accepted for publication – Journal of Materials Chemistry

Bassett DC, Grover LM, Müller FA, McKee MD, Barralet JE. Serum protein controlled nanoparticle synthesis. In press – Advanced Functional Maerials.